Title: Phys 3120 / Midterm 2
Tags: RenalSystem CardiovascularSystem BasalGanglia MotorCortex SpinalReflexes SkeletalSystem Cerebellum Transporters

Stretch Reflex
1. Stretch quadriceps muscle (knee extensor), opening ion channels.
2. Action potentials in 1a afferents in quadriceps muscle.
3. Action potentials of of quadriceps alpha motor neurons.
4. Contraction of stretched muscle.
5. Reciprocal inhibition of knee flexor muscles (hamstring) via postsynaptic inhibition of antagonist alpha motor neuron.
- Location: Completely contained within a single part of the  spinal cord.
  - If you see a particular stretch of a muscle, you can determine if there is an issue in a certain level of the spine.

Q: - An [...] is the recording of [...] associated with action potentials in skeletal muscle.
A: electromyogram (EMG); extracellular current flow

- There is no stretch reflex for slow stretches because EPSPs do not summate fast enough to produce action potentials.
- During a fast stretch (eg. tap), temporal summation of 1a spindle occurs and an AP is sent from the spindle to the spinal interneuron.
  - This is not all-or nothing, the faster the tendon tap the greater the response of the motor neuron.
  - Interneuron sends excitatory response to extensor (what was stimulated) and inhibition of flexor.
  - Homonymous activation of muscle (same muscle activated as stimulated).

Q: - [...] is the passive resistance which occurs when a healthy person is asked to relax and a muscle is stretched This is because of the [...] properties of the muscle.
A: Muscle tone; viscoelastic

Q: - The flexion reflex will occur even in [...].
A: paraplegics

Q: 6. List 2 characteristics of the scratch reflex
1. Programmed within the [...].
2. [...] specific.
- Note: Typically itching is an [...] stimulus (eg. a flea) so the scratch reflex can be automatic (eg. in a puppy).
A: spinal cord; Site; irritating

Q: - The neural circuits (pattern generator) for [...] are located in the [...]. (headless chicken)
A: locomotion; spinal cord

Q: - [...] cortex is the [...] gyrus and part of the cerebral cortex from which electrical stimulation elicits [...].
A: Motor; precentral; muscle contractions

- There is somatotropic organization for the postcentral gyrus (somatosensory cortex) and the precentral gyrus (motor cortex).
  - From lateral to medial: tongue, face, hands, elbow, shoulder, trunk, leg.
  - Notice, our tongue is overrepresented here compared to the somatosensory cortex, since we need our tongue for speech but don’t get much info from it.

Q: 1. Particular muscles can be activated by stimulating [...] cortical sites in the motor cortex.
- No clear clustering of muscles in the motor cortex.
A: widely dispersed

Q: Evidence that somatotropic organization is plastic (modifiable).
1. Learning: Size of the finger representation in motor cortex was measured. Subjects then learned a complex task after which fMRI showed an [...] in the size of [...] representation in motor cortex.
A: increase; finger

Three output pathways from the motor cortex.
1. Corticospinal tract (aka pyramidal tract).
- Some synapse directly onto motor neurons and are called corticomotor neurons.
- Most neurons synapse with spinal interneurons, which then synapse to motor neurons.
- Can be inhibitory, if you get rid of the inhibition you get spasticity.

Q: - Phylogenetic development of Pyrimidal Tract
  - Only occurs in [...].
- Termination
  - About [...] of axons make [...] connections with alpha motor neurons.
A: mammals and shows progressive development up mammalian tree (esp. in primates); 10%; monosynaptic

- A large motor cortex lesion causes weakness (or paralysis) as well as spasticity.
  - Spasticity involves both a spinal component and the loss of inhibition from motor cortex.
  - Most dramatic effects are for distal muscles (eg. hand).
  - Note: The faster you get treatment, the better you can recover some movements.

Pyrimidal Tract Neurons
1. Some discharge before movement onset.
2. Some discharge preferentially for one direction of movement.
3. Some discharge proportional to force or rate of change of force.
- Neurons have basal fire rate, increasing in ideal direction and decreasing in opposite.
- These neurons respond to force generation (if arm is constrained they will still fire.

Time Delay in Motions
1. Conduction time from cortex to spinal cord.
2. Time for summation to threshold in alpha motor neurons.
3. Conduction time from spinal cord to NMJ.
4. Synaptic delay at NMJ (1 ms).
5. Electrical mechanical coupling time.
- Ie how long it takes to overcome mass/inertia of limb after AP in muscle.

- Cerebellum comes from Latin meaning “little brain”.
- The cerebellum consists of only 10% of the volume of the brain but over 50% of the neurons.
- The same basic neuronal circuit is present all across the cerebellum.
- Two separate input streams
  - Mossy fibers carry information from various places, then synapse with a granule cell and form parallel fibers.
  - Climbing fibers carry information from inferior olive.
  - Main difference is parallel fibers make many synaptic connections to many purkinje cells, and climbing fibers make many synaptic connections to one purkinje cell.
- One output, from deep nuclei via purkinje cells (inhibitory).
- Lesions in the cerebellum cause movements which are inaccurate and uncoordinated.

Cerebellum Output
1. Widespread sensory input. None reaches consciousness.
2. Only output from cerebellum is through the deep nuclei via Purkinje cells.
- Always inhibitory action.

Q: Effects of Lesions in cerebellum
- Lateral cerebellum
- Dysmetric [...] movements.
- [...] Tremor.
- [...] Ataxia.
A: limb; Intention; Arm

Q: - The cerebellum is like a computer that automatically (subconsciously) [...] reflexes and motor movements to make them [...].
- Essentially supports all functions of the cortex.
A: tunes-up; more accurate

Q: Functions of cerebellum
1. Contributes to the generation of accurate [...] and [...] movements.
- Every time a saccade or voluntary limb movement is made, the cerebellum helps [...].
A: saccade; limb; start and stop it, and make it accurate

Q: Parts of Cortex which interact with motor cortex
1. [...] cortex.
2. [...] cortex.
3. [...] cortex.
A: Supplementary motor; Premotor; Parietal

Q: Basal Ganglia
1. There are at least [...] separate circuits (loops) from cerebral cortex, through the [...] and back to the cerebral cortex (also go through [...]).
A: four; basal ganglia; thalamus

- Basal ganglia exerts continuous inhibition, preventing unwanted movements.
- To make a movement, basal ganglia takes off the breaks.
  - Akinesia: Can’t take off the breaks so you get no movement.
  - Hyperkinetic: Lack of breaks means you get excessive movement.

- MPTP
  - In the 80s, some people took an IV of what was thought to be synthetic heroin, but it was contaminated with MPTP, depleting their dopamine levels.
    - Overnight they developed Parkinson’s symptoms.
- Two positive outcomes:
  - MPTP can give us an animal model for Parkinson’s.
  - Parkinson’s has both genetic and environmental factors (also confirmed through exposure of rats to rotenone.

Parkinson’s Disease: Loss of dopaminergic neurons in the substantia nigra.
- Rigidity (not spasticity, it is not velocity dependent).
- Difficult to initiate movements.
  - Eg. Can ride a bike, since the bike is pushing him along, but can’t initiate the movement himself.
- Resting tremor (stops during movement, pill rolling motions).
- Akinesia (lack of movement).
- Bradykinesia (slowed movement, shuffling gait).
- Dementia
- Mask-like face.

- Increase in discharge in neurons in the globus pallidus in Parkinson’s, increasing inhibition of thalamus and decreasing excitation of the motor cortex.

Chorea (decreased output from GP means less inhibition of motion).

- Treatment for Parkinson's:
- Enhance dopaminergic transmission using L-dopa.
  - Try to increase dopamine and decrease Ach.
  - But note, too little dopamine causes akinesia, too much causes involuntary movements (dyskinesia).
- Optical flow can keep basal ganglia on, improving motion.
- Lesion internal segment of globus pallidus, helping certain movements.

Huntington’s Disease: Degeneration of neurons in caudate and putamen. Causes abnormal protein folding and cell death.
- First signs are subtle: absentmindedness, clumsiness, falls.
- Uncontrolled movements gradually increase until patient is confined to a bed.
- Speech is slurred at first, then incomprehensible and finally stops altogether as their facial expressions become distorted and grotesque.
- Features
  - Heritable.
  - Chorea (decreased output from GP means less inhibition of motion).
  - Hyperkinetic
    - Can’t maintain a movement, without having to change it and make another movement.
  - Dementia (limbic, cognitive loops).
  - No treatment available.

Q: Other disorders of Basal Ganglia
- [...]: [...] movement due to lesion in [...].
A: Hemiballismus; Violent limb; subthalamic nucleus

Functions of the CV System
- Homeostasis!: Maintains the internal environment.
1. Transports oxygen and nutrients to the tissues.
2. Transports CO2 and waste products from the tissues to the external environment.
3. Helps regulate body temperature.
4. Transports and distributes hormones and other substances within the body.

CV System
Components
1. A central pump - the heart
2. A closed system of blood vessels
- 2 circulatory systems.
  1. Pulmonary Circulation (to and from the lungs).
  2. Systemic Circulation (to the rest of the body).
- Note: Oxygen-rich blood is always bright red, poor blood is {{c2:dark}} red.

CV System
Circulatory Systems
Pulmonary
- Right atrium -> Right ventricle -> Pulmonary artery -> Pulmonary Capillaries.
- Picks up O2 as it passes through the lungs and drops off some CO2.
  - Not all CO2 leaves the blood.
Systemic
- Pulmonary Vein -> Left atrium -> Left Ventricle -> Aorta -> Arteries -> Arterioles -> Capillaries → Venules -> Veins -> Vena Cava.
  - Capillaries are the site where O2 leaves the blood into tissue and CO2 and waste are picked up.

Series and Parallel Circuits
- Vascular (capillary) beds are arranged in parallel and series.
- Ascending arteries go to the arms and head.
- Descending arteries go to anything below the diaphragm.
- Note: Digestive tract and the liver are in series with each other, but the liver also gets a direct artery from the heart.
- Kidney glomerular capillaries and PT capillaries are in series.
Advantages
1. Amount of blood flow to individual vascular beds can be controlled separately.
2. Relatively low resistance to blood flow;

Blood Volume Distribution
- Total Blood Volume (TBV) = 5L.
  - 3L of Plasma and 2L of other stuff.
- Pulmonary circuit (incl. heart) = 15%.
- Systemic arterial system (distribution vessels) = 10%.
- Systemic capillaries (exchange vessels) = 5%.
- Systemic veins (capacitance vessels) = 70%.

Anatomy of the heart
- One pulmonary vein and artery per lung.
- Superior vena cava brings blood back from above diaphragm.
- Inferior vena cava brings blood back from below diaphragm.
- Left ventricle is thicker since it needs to generate more force.
- Note the Apex of the heart (bottom).
- Ventricular pressure closes the tricuspid and bicuspid valves.
  - Chordae Tendonae attach to papillary muscles to keep valve from blowing backwards into the atrium.
- Semilunar valves close when the ventricles relax, preventing backwards flow of blood.

Q: Myocardial Cells
- Two types:
1. [...] (atrial and ventricular muscle cells).
1. Specialized Excitatory (nodal) and conducting cells:
2. - Excitatory nodal cells: [...] nodes.
3. - Conducting cells: [...].
A: Contractile Cells; Sinoatrial (SA) & Atrioventricular (AV); Bundle of His and Purkinje Fibers

Contractile Cells (Atrial and ventricular muscles)
- Similar to skeletal muscle:
  - Striated and contain actin and myosin.
  - Contraction requires presence of Ca2+.
- Differences:
  - Shorter, branched and arranged in series.
  - ⅓ of volume is mitochondria (for ATP).
  - Extract 80% of O2 from the blood.
  - Joined by intercalated discs containing gap junctions.
    - Electrical resistance through the gap junctions is low.

Origin of Self-excitability
- Normal heart rate = 72 bpm (in vivo).
- APs originate in the sinoatrial (SA) node in the upper posterior wall of right atrium.
- Most heart cells are self-excitable, but the SA node produces APs the fastest.
  - It is the pacemaker of the heart.
  - A heart AP takes 0.8 seconds.

SA Node & Excitation
- Characteristics responsible for self-excitation:
1. Greater Na+ and Ca2+ permeability (positive inwards current).
2. K+ permeability decreases during diastole (relaxation phase).
- Less K leaves during relaxation.
- SA nodal cells don’t have a stable resting membrane potential.
  - Pacemaker potential is from -60 -> -40 mV.
  - General membrane potential varies from -60 -> 20 mV.

Diastole (ventricular relaxation)
1. Slow, spontaneous depolarization (pacemaker potential) is caused by:
- Increased permeability to Na+ through funny channels.
  - Open when the cell is hyperpolarized, not depolarized.
- Increased permeability to Ca2+ through T-type and L-type channels.
  - T-type is faster than L-type.
- Decreased permeability to K+.
- Ie) More Na+ and Ca2+ in, and less K+ out.

Conducting System of the Heart
- SA node sends AP from the top of the atrium downwards.
  - Goes to left atrium through interatrial myocardial band.
- AP spreads to the contractile cells downwards.
  - Pushes blood into ventricles.
- To make the ventricles contract bottom up, the atrioventricular ring must electrically isolate the atria from the ventricles.
- Internodal pathway takes the AP down from the SA node to the AV node.
  - In the AV node, the AP speed slows down, to allow the atria to finish contracting before the ventricle starts.
- Bundle of His transfers AP from AV node to the apex of the heart.
- Purkinje fibers in the apex rapidly transmit the AP to the ventricular contractile cells.

Speed
- Notice, the AP speed is slow in both nodes, & fast in the contractile tissue.
- Fastest AP speed occurs in purkinje fibers.
Pacemaking
- SA node has an intrinsic rate of 90 beats/min.
  - At rest our PNS is active so it makes the heart beat at 60-70 bpm.
- If the SA is damaged, AV node or Purkinje fibers can take over pacemaking.
  - AV node discharges at 40-60 bpm.
  - Purkinje fibers fire at 15-40 bpm.
  - These both generate APs, but just slower than the SA node.

Q: Electrocardiogram (ECG)
- Electrodes placed on skin can give[...] values for the APs.
- [...]: [...].
A: vector; P-wave; Depolarization of atria

ECG Intervals
PR Interval
- Time it takes AP to travel from SA node to the  AV nodes and ventricles.
  - From the beginning of P to Q.
  - Good estimate of AV node function.
- PR interval decreases as heart rate increases.
  - ANS increases conduction speed through the AV node.

Clinical Scenario #1
- Male w/ shortness of breath and 35 bpm heart (bradycardia).
- ECG has normal P waves (& normal intervals), but fewer QRS complexes, which also don’t align well with the P waves.
  - Slower rate of QRS firing leads to slow heart rate.
Q) Where is the damage?
- Something is likely wrong in the AV node, or the bundle of his.
- Atria is fine since the SA is fine, but the action potential is not getting to the ventricles so the purkinje fibres have taken over pacemaking duties
Q) Why do they have bradycardia?
- Purkinje fires much slower than the SA node.
Q) How to fix it?
- Add a pacemaker which monitors the SA and fires below the site of damage.

- Function: Stretch reflex is the first line of defense against unexpected muscle stretch.
  - Tries to return muscles to pre stretched length.
  - Tonic excitatory input brings the membrane potential so close to threshold that a minor 1a muscle spindle activation can activate the stretch reflex.

Q: - Latency: The latency of the stretch reflex is about [...] ms compared to a voluntary reaction time of >150 ms.
  - Fast but [...].
  - There is only one synapse involved!
A: 30; dumb

Q: All spinal reflexes have [...] inhibition of antagonist muscles.
A: reciprocal

- In a spinal reflex, Ipsilateral flexion (withdrawal) is paired with a crossed extensor reflex.
  - Eg. Put a tack in foot, knee/hip flex to remove foot (spinal response on same side as noxious stimulus), but some neurons cross over to activate extensor muscles of opposite leg.

1. After discharge: period of withdrawal outlasts noxious stimulus. This occurs because:
- Nociceptors continue to discharge.
  - Reverberating activity in the spinal cord circuitry.
  - Positive feedback loop of interneuron activating itself.

Q: Local sign of spinal reflex: Exact [...] depends on the site of stimulation.
- Not pure flexion
A: withdrawal pattern

Q: - In some clinical conditions (spinal cord injury, stroke) additional muscle resistance arises because of inc. sensitivity to the stretch, this is called [...].
A: spasticity

Q: - Spasticity is [...] dependent because the receptor activated by muscle stretch is the [...], whose discharge is proportional to the [...] of the stretch.
A: velocity; Ia afferent; velocity

- Resting membrane potential of the alpha motor neuron is closer to threshold in spasticity (due to loss of inhibition from motor cortex).
  - Muscle stretch itself causes normal discharge, but in spasticity, stretches that don’t normally summate to threshold do reach threshold.
    - Ie. Same size EPSPs reach threshold in spastic people, but not regular.
- We can use operant conditioning to try and fix the spinal reflex.
  - With a lot of effort and practice, people are able to some degree control the sensitivity of their spinal reflex and reduce baseline.

- Evidence for Somatosensory organization of motor cortex:
  - Map inferred by Hughlings Jackson from observation of epileptic motor seizures.
  - Confirmed by electrical stimulation in human patients (conducted by Penfield).
  - Lesion in this area causes paralysis (severe) or weakness.
    - Cut of medial side of right precentral gyrus causes paralysis of left leg.

Q: 1. Single motor cortical neurons make monosynaptic connections to [...] innervating [...] muscles.
A: motor neurons; multiple

Q: 1. Motor cortex stimulation can produce [...] movements (eg. bring food to mouth).
- Muscles are thus activated somewhere in the [...], but [...] are in the brain.
A: purposeful; spine; movements

Evidence somatotropic organization is plastic
1. Studies of experimental injury: Artery of hand region of motor cortex blocked in monkeys. Neurons controlling the hand died and the monkeys lost hand movements as well as hand region of motor cortex, gaining some movement back after training.
- Trained monkeys now had hand representation in the elbow/shoulder part of the motor cortex, non-trained monkeys had no hand representation.

Q: Three output pathways from the motor cortex.
[...] tract: From motor cortex to the [...] in the brainstem.
- Important for [...] scale movements.
A: Corticorubral; red nucleus; large

Q: Three output pathways from the motor cortex.
[...] tract: From motor cortex to the [...] in the brainstem.
- Important for [...] scale movements.
A: Corticoreticular; reticular formation; large

- Lesion of Pyrimidal Tract
  - Monkeys with lesions of the pyramidal tract appear at first sight to be fairly normal (ie can walk, run, climb).
  - Major effect of pyramidal tract lesion is the loss of refinement of movements, especially for movements in the hand.
- Evolution
  - The pyramidal tract and dorsal column medial lemniscal system coevolved, presumably for the accurate identification and manipulation of objects.

Cerebellum Outputs
1. Medial and lateral division anatomically/physiologically/neurologically.
2. In monkeys/humans there is increased development of the lateral cerebellum.
- Lateral cerebellum is occupied by projections to the cerebral and motor cortices, as well as processing information from somatosensory system.
- Information typically goes to the thalamus and then onwards.
- Dentate nucleus is particularly involved in refining activity of limbs.
  - Need cortical control for fine control but not crude movements.
- Red nucleus controls proximal limb motor neurons (for posture).

Cerebellum Outputs
Medial cerebellum always relays through the fastigial nucleus and/or the vestibular nuclei, being strongly involved in posture (lateral) or eye movement (medial).

Q: Effects of Lesions in cerebellum
- Medial cerebellum
  - Dysmetric [...].
  - Disorder of [...] movements.
  - [...] Ataxia.
A: saccades; smooth pursuit eye; Gait(drunk

Effects of Lesions in cerebellum
- Many of the effects of cerebellar lesions are mimicked by alcohol (GABA).
- Disorders occur due to failure of the cerebellum to “tune-up” different functions.
  - E.g Failure to tune-up generation of saccades (reticular formation), limb movements (motor cortex) and balance.
  - Not necessarily an abject failure, but just not fine functioning (saccades aren’t smooth, limbs tremor, posture is bad).
- You can even be born without a cerebellum, resulting in poor fine control.

Q: Functions of the cerebellum
1. [...] movement control.
- When perturbation is expected, the movements which occur are based on [...] control.
  - Eg. If a ball is dropped onto the hand, visual information is used by cerebellum to predict the time of impact.
  - If cerebellum is lesioned, related issues such as [...].
A: Feedforward/ anticipatory; feedforward (anticipatory); planning out future goals

Functions of the cerebellum
1. Motor recalibration.
- When encountering changes in the environment, the cerebellum learns to recalibrate movements and reduce errors.
- May work through changing the strength of the parallel fiber/Purkinje cell synapse, or by changing the input from climbing fibers (teacher).
- Cerebellar patients can’t recalibrate well.
  - Eg. On the dart throwing experiment, a healthy participant throws poorly for only a few darts after putting on prism glasses, but then adjusts, only throwing poorly if they then take off the glasses.
  - Cerebellar patients would throw poorly the entire time the glasses are on, but well as soon as they were taken off since no learning occurred.

Functions of the cerebellum
1. Contributions to cognition
- Sensory discrimination: Cerebellar patients can’t discriminate the duration of auditory tones or velocity of objects accurately.
- Spatial cognition: Cerebellar patients don’t perform well on these tasks.
- Linguistic processing: Cerebellar patients don’t perform well on noun-verb matching (dog-bark).

Basal Ganglia
1. Two inputs to caudate/putamen (from cerebral cortex and substantia nigra).
2. Major transmitters are dopamine(excitatory or inhibitory), Ach, and glutamate.

Q: Basal Ganglia
1. From the caudate/putamen to the internal globus pallidus, there is a direct and indirect (via [...]) pathway.
A: subthalamic nucleus

Q: Basal Ganglia
1. Output is from the [...] to the thalamus (inhibitory).
A: internal globus pallidus

Q: Lesions in Basal Ganglia Loops
- Oculomotor
  - Eye movements ([...] saccades).
A: fewer and slower

Q: Lesions in Basal Ganglia Loops
- Limbic
  - Emotion (particularly [...]).
A: irritability and depression

Q: Lesions in Basal Ganglia Loops
- Cognitive
  - [...], working memory, attention, [...] disease.
A: Planning; tourettes

Q: In Parkinson's disease you have an [inc/dec] in discharge from the [...], [inc/dec] activation of the thalamus.
A: increase; globus pallidus; decreasing

- Other Disorders of Basal Ganglia
- Tourette’s: Inappropriate utterances (coprolalia), tics (repetitive and involuntary movements), due to excessive activity of cognitive basal ganglia circuitry.

Contractile Cells of the Heart
- Functional Syncytium: When one cell contracts, they all contract.
  - 2 separate functional syncytium:
    - Atrial Syncytium
    - Ventricular Syncytium
  - Separated by atrioventricular ring.
    - Allows atria to contract before the ventricles.

Q: Specialized Excitatory (Nodal) and Conducting Cells
- Contain few contractile elements, so they contract [...].
- [...]: Spontaneously generate APs.
  - Act more like [...].
A: weakly; Self-excitable; nerves

Q: Diastole (ventricular relaxation)
1. Depolarizing phase (begins at threshold) is caused by:
- [...] channels close.
- All slow [...] channels open.
  - Ca2+ flows in to +20 mV.
A: Na+ funny & T-type Ca2+; L-type Ca2+

Q: Diastole (ventricular relaxation)
1. Repolarization is caused by:
- [...] channels close.
- [...] channels begin to open ([...] outwards K+).
  - Returns membrane potential to -60 mV.
A: L-type Ca2+; K+; increased

Q: Electrocardiogram (ECG)
- [...]: [...].
  - Bigger than P-wave since ventricles contract more.
A: QRS-complex; Depolarization of the ventricles

Q: Electrocardiogram (ECG)
- [...]: [...].
A: T-wave; Repolarization of Ventricles

Electrocardiogram (ECG)
- U-wave: Repolarization of Papillary Muscles in Ventricles.
  - Depolarization of papillary muscles occurs in the QRS complex.
- Where is repolarization of the atria?
  - Somewhere in the QRS complex!

Q: ECG Intervals
QRS Duration
- Indication of speed of conduction through [...] system
- Narrow: [...].
- Wide: Slow, [...]
A: bundle of his- purkinje; Fast, AP properly propagating; AP may be jumping to the ventricles through another pathway.

AP in Ventricular Contractile Cells
- Duration is 300 ms.
- Phases:
  - 0: Depolarization.
  - 1: Rapid Repolarization.
  - 2: Plateau Phase.
  - 3: Restoration of resting potential.
  - 4: Resting potential.
- Goes from -90 -> +20 mV.

Q: AP in Ventricular Contractile Cells
- 0: Current from neighbouring cells [...] the cell (through gap junctions).
  - VG [...] channels open, and [...] enters inwards rapidly, up till +20 mV.
A: depolarizes; Na+; Na+

AP in Ventricular Contractile Cells
Rapid Repolarization
- 1:  Na+ permeability decreases, and Na+ channels close.
  - Cl- channels open and Cl- flows inwards (briefly).
  - While VG K+ channels open and K+ begins moving out.

AP in Ventricular Contractile Cells
Plateau Phase
- 2: AP opens slow (L-type) Ca2+ V.G channels and Ca2+ moves inwards slowly, decreasing the rate of repolarization.
  - Balances out with outwards K+ current, creating a relatively stable plateau.

Q: AP in Ventricular Contractile Cells
Return to Resting Potential
- 3: [...] channels begin to close.
  - Inward movement of [...] decreases while K+ continues to move outwards.
A: Slow (L-type) Ca2+; Ca2+

Q: Refractory Periods in Ventricular APs:
1. Absolute refractory period:
- Due to inactivation of fast [...] channels (and possibly [...] V.G channels).
- Lasts about 250 ms.
1. Relative refractory period:
- Mainly [...] efflux.
A: Na+; Ca2+; K+

Q: Excitation-Contraction Coupling (ECC) in Heart
- AP in contractile cells leads to release of [...] from SR causing a muscle contraction.
- Similar to skeletal muscle:
  - AP on cell membrane (sarcolemma) spreads to [...].
  - Opens and releases Ca2.+ from [...] (into intracellular fluid).
A: Ca2+; T-tubules; SR

Excitation-Contraction Coupling (ECC) in Heart
- Different from skeletal muscle:
  - Extracellular Ca2+ enters sarcoplasm (cytosol) during depolarization of the sarcolemma (membrane).
  - This extracellular Ca2+ can interact with dihydropyridine (DHP) receptor in SR to cause further release of Ca2+ from SR.
    - This is called Ca2+-induced Ca2+-release (CICR).
    - Dihydropyridine (DHP) receptor is just a slow L-type Ca2+ channel!
- Should note, there is DHP in both the skeletal muscles and cardiac muscles, but in cardiac muscles it acts as a channel rather than a voltage sensor.

Q: Free [Ca2+] can be increased by:
1. [...] induced Ca2+ influx from ECF through slow, L-type Ca2+ channels (DHPR/Ca2+ channel).
- Ca2+ is useful both for the [...] as well as interacting with the thin myofilaments to create contraction.
A: Depolarization; plateau phase

Free [Ca2+] can be increased by:
1. Ca2+ can enter through Na+/Ca2+ exchanger.
- Pump is bidirectional and switches when membrane potential is positive and [Na+]i is high.
- Typically pumps 1 Ca2+ out and 3 Na+ in.
- During depolarization it flips direction! Ca2+ travels in and 3 Na+ out.

Q: Free [Ca2+] can be increased by:
1. Extracellular Ca2+-induced Ca2+ release.
- Ca2+ that entered thru slow L-type Ca2+ channel and Na+/Ca2+ exchanger can open the [...] channel on SR.
- Depolarization may also directly open [...] channels.
A: ryanodine/Ca2+; ryanodine/Ca2+

Q: Free [Ca2+] can be increased by:
1. Intracellular Ca2+-induced-Ca2+ release from SR.
- Ca2+ from [...] can open other ryanodine Ca2+ channels (on [...]) to release more Ca2+ (positive feedback loop).
A: SR; SR

Q: Comparison of DHP-RYR Ca2+ channels in:
1. Skeletal muscle
- DHP is a [...] directly linked to the SR.
1. Cardiac muscle
- [...] channel.
A: voltage sensor; Slow L-type Ca2+

Cardiac Muscle Contraction
- Similar to skeletal muscle.
- Ca2+ binds to troponin.
- Troponin pulls tropomyosin off myosin binding sites.
- Myosin attaches to actin forming crossbridge.
- Powerstroke occurs.
- Sliding of myofilaments.

Cardiac Muscle Relaxation
- Relaxation is brought about by lowering [Ca2+]i.
1. Ca2+ is actively pumped back into the SR by Ca2+ ATPase (80%).
2. Ca2+ is actively pumped out of cell into ECF by similar Ca2+ -ATPase (5%).
3. Na+/Ca2+ exchanger on sarcolemma pumps 1 Ca2+ out for every 3 Na+ in (15%), ie) during rest.

Q: Temporal Relationship of AP and Contractile Response
- Contractile/mechanical response begins just after the start of [...] and lasts for 250 - 300 ms.
- Response of cardiac muscle occupies most of the [...] of the ventricular AP.
- When ARP ends, more than [...] of the contractile response is over.
A: depolarization; absolute refractory period; 75%

Q: Difference between Cardiac and Skeletal Muscle
- You can summate the twitches in skeletal muscle since the contraction ([...] ms) lasts [...] than the AP (2ms).
- You cannot summate cardiac muscle twitches since you are still in the absolute refractory period of an AP when you are finishing your contraction.
  - Ie) [...] contractions can’t occur in cardiac muscle.
A: 15; longer; Tetanic

Q: The Cardiac Cycle
Consists of a period of ventricular
- Diastole/relaxation ([...] s)
- Systole/contraction ([...] s)
A: 0.53; 0.27

The Cardiac Cycle
Important Factors
- Blood flows in one direction through the heart (valves prevent backflow)
  - Atria to the ventricles (AV valve must be open)
  - Ventricle to the aorta (Aortic valve must be open)
- For blood to flow you need a pressure gradient:
  - High to low and blood will flow (1 exception)
    - E.g For blood flow from the atria to the ventricle, you need a higher pressure in the atria.
- When blood is flowing, ventricular volume will change.
- When all valves are closed, there is no blood flow and the ventricular volume will not change.

The Cardiac Cycle
Step 1 Atrial Systole (contraction)
- P wave (depolarization of atria) contracts, leading to atrial contraction.
- Increased atrial pressure is greater than ventricular pressure (AV valves are already open).
- Ventricles fill (last 30%) up to end diastolic volume (EDV).

The Cardiac Cycle
1. Step 2 Isovolumetric (ventricular) contraction
  1. QRS complex, leads to ventricular contraction, building ventricular pressure.
  2. Ventricular pressure is greater than atrial pressure, closing the AV valves (first heart sound).
    1. Atrial pressure inc. slightly due to pushing from ventricle onto the AV valve.
  3. No change in ventricular volume.

The Cardiac Cycle
Step 3: Rapid Ejection Period
  1. Ventricles continue to contract.
  2. Ventricular pressure is greater than aortic pressure, thus the aortic valve opens and blood leaves the ventricles.
  3. Ventricular volume decreases.
  4. T-wave (repolarization of the ventricles).

The Cardiac Cycle
Step 4: Protodiastole (early relaxation).
- Ventricles begin to relax.
- Ventricular pressure dec.
- Aortic pressure is higher than ventricular pressure because the blood is still moving into the aorta due to inertia.
- Left with end systolic volume (ESV) after some more blood leaves.

The Cardiac Cycle
Step 5: Isovolumetric ventricular relaxation.
- Ventricles continue to relax.
- Ventricular pressure > atrial pressure, but all valves are closed.
- Blood changes direction, closing the aortic valve (2nd heart sound).
-- Accompanied with a brief rise in aortic pressure (called insicura), due to the blood trampolining off the closed valve.

The Cardiac Cycle
Step 6: Rapid Inflow
- Ventricles relaxing.
- Ventricular pressure < atrial pressure, opening the AV valve.
- Blood fills most of the ventricle

The Cardiac Cycle
Step 7: Diastasis
- Ventricles relaxing.
- Ventricular pressure is still < atrial pressure.
- Blood enters ventricles slowly.
- Cycle repeats.

Heart Sounds
- First Heart Sound - “lub”
  - The sound results from vibrations in the blood and muscles associated with the sudden block of flow reversal by AV valves (prevents flow back into atria).
- Second Heart Sound - “dub”
  - Caused by vibrations in the blood, muscles and aorta associated with the sudden block of flow reversal by the aortic valve.
    - When the ventricles relax and the blood is drawn backwards.
- Third Heart Sound
  - Not often heard, but sometimes in young children.
  - Blood hitting the wall of the ventricle, which is not very compliant.

Cardiac Output
1. Control Cardiac output through changes in HR (primarily).
2. Or, control output through changes in stroke volume.
- Cardiac output (CO, Q) is the vol. of blood (L), pumped by the ventricle per minute.
- CO is matched to the oxygen demands of the body.
- At rest, CO = 5L/min (regardless of fitness).
- Maximal exercise, CO = 20-40 L/min (depends on fitness level).
- Cardiac output = heart rate x stroke volume.
  - 72 bpm x 70 mL = 5L/min.
  - Stroke volume is the amount of blood ejected from the ventricle when it contracts (roughly 70 mL at rest).
    - Changes in endurance athlete since their heart becomes larger.
    - At rest, their resting bp is lower, but stroke volume is higher.

Blood Flow distribution under basal (resting) conditions
- Brain requires 14% of the cardiac output.
- Kidneys require 22%, since they filter so much blood.
- Liver requires 27%, it is the most metabolically active organ (and largest).
- The heart is very efficient and only requires 4%.
- Inactive muscle / other tissue is each 15%.
Recall, heart rate is set by the SA node and can be altered by changing the slope of the pacemaker potential or hyperpolarization of the membrane potential.

Blood Flow distribution under basal (resting) conditions
- Heart rate is controlled primarily by the autonomic nervous system (ANS).
  - SNS causes an increase in heart rate, thus inc. CO, from rel. of noradrenaline onto adrenergic, or Ach.
  - PNS causes a decrease in heart rate, thus dec. CO, from rel. of acetylcholine.
  - PNS (vagus) nerves are distributed mainly to SA and AV nodes and have a small effect on the ventricular muscle.
    - If you slow down SA, you also should slow down AV.
  - SNS nerves are distributed to the SA and AV nodes with a strong input to ventricular muscle.

Effects of PNS (Vagal) stimulation
1. Decreases HR (negative chronotropic response).
- By decreasing SA node activity.
1. Decreases AP conduction through the AV node.
2. Decreases contractile force slightly (-ve inotropic effect).

Effects of PNS (Vagal) stimulation
Mechanism
- Ach binds to muscarinic (M2) receptors, inc. K+ permeability and hyperpolarizing.
  - Also get dec. Ca2+ permeability (T-type channels).
  - Decreased sodium permeability (funny channels).
- With more K+ leaving and less cations entering SA node cells, decreases the slope of the pacemaker potential.

Q: Effects of SNS stimulation on the Heart
1. Increase HR (+ve [...] response).
2. Increases AP conduction through the [...] node.
3. Increase force of [...] (+ve inotropic effect).
A: chronotropic; AV; contraction

Effects of SNS stimulation on the Heart
Mechanism
- Norepinephrine binds to B1 adrenergic receptors.
  - Increases Na+ permeability (funny channels).
  - Increased Ca2+ permeability (T-type channels).
- Inc. pacemaker potential slope.
- AV node: Increased sodium and calcium permeability decreases conduction time between atria and ventricles.
  - Decreased PR interval!

Q: Maximum Heart Rate
HR = [...]
OR more accurately
HR = [...] - ([...])
A: 220 - age; 205.8; 0.685*age

Q: Stroke Volume = [...] - [...]
A: EDV; ESV

Stroke Volume
-
SNS Stimulation (increases HR).
- Norepinephrine binds to B1 adrenergic receptors in contractile cells.
  - Increased calcium permeability (L-type channels).
    - Increases force of contraction (ECC), increasing stroke volume and CO.
- Acetylcholine released onto adrenal gland.
  - Releases epinephrine (and NE) acting on B1 adrenergic receptors.
    - Increases HR in the SA node.
    - Increases calcium entry and contractility of the heart.

Q: Stroke Volume
-
SNS Stimulation (increases HR).
How do heart transplant patients increase HR?
- A heart transplant patient can increase HR and SV during physical activity by activating the SNS, which makes the [...] secrete [...].
A: adrenal gland; epinephrine

Q: Stroke Volume
PNS Stimulation (decreases HR).
- Remove all [...] activity.
- [...] nerve innervates left ventricle:
  - Closes some [...] channels, causing decreased entry into contractile cells (dec. force).
    - Dec. stroke volume and CO.
A: SNS; Left vagus; L-type calcium

Stroke Volume
Preload
- Extent of the filling of the heart before contraction.
  - Directly related to EDV (inc. in EDV causes inc. preload/stretching of muscle).
  - Higher stretch = greater contractile force.

Stroke Volume
Increased EDV
- Stretched ventricles (preload).
- Length of vent. muscle increases.
- Stretched fibers generate more force due to higher overlap of actin and myosin (can plateau).
  - High EDV stretches the sarcomeres to an ideal length for contraction.
- Also, may open stretch sensitive calcium channels.
- Stretch can also inc. troponin’s affinity for calcium.

Stroke Volume
Frank-Starling Law of the Heart
- Greater the heart is filled during diastole, the greater the quantity of blood pumped during systole.
- Effects of ANS input on the Frank-Starling curve.
  - At a given EDV:
  - A) Normal
  - B) SNS increases stroke volume (+ve inotropic effect).
  - C) PNS decreases stroke volume (-ve inotropic effect).

How exactly do you increase EDV?
- Increase venous return to the heart!
1. Muscle Pump.
2. Respiratory pump.
3. Autonomic nervous system.

Q: How exactly do you increase EDV?
1: Muscle Pump:
- Rhythmic [...] and [...] of skeletal muscle pumps blood back into the [...].
  - Occurs when you swim, walk, cycle etc.
A: contraction; relaxation; heart

Q: How exactly do you increase EDV?
2. Respiratory Pump:
- [...] pressure in the chest cavity.
  - Expand chest outwards, diaphragm [...] (comes down), increasing the volume of the chest cavity and [...] pressure.
- Pulls blood back to the heart!
A: Decreases; contracts; decreasing

Q: How exactly do you increase EDV?
3. Autonomic Nervous System.
- SNS causes slight [...], increasing venous return to the heart.
A: venoconstriction

Clinical Scenario: Orthostatic Hypotension
- An elderly patient complains they feel light headed and have passed out after standing up from a sitting or lying position.
- Triggered by standing (orthostasis) after a long period of lying down.
  - Drop in blood pressure of Systolic (20 mmHg) over Diastolic (10 mmHg).
Q) What cardiovascular factors are affected?
- Standing makes blood flow out of the thoracic cavity at 700 mL/s.
  - Decreased venous return, decreased EDV/SV/CO.
- Decreased MAP (mean arterial pressure) also occurs.
Q) How do these cause the feeling of light-headedness?
- Blood flow out of the head gives the feeling of a head rush.
Q) Why are the elderly more susceptible?
- Old people have a slower reflex to restore blood pressure, plus they may be on meds to keep their blood pressure low.

Vascular Function (blood vessels)
Cross Sectional Area and Velocity of Blood Flow
- Consecutive branches of the arterial system, vessels become smaller.
  - You get a larger number of blood vessels however, leading to a great increase in total cross sectional area.
- Eg. Aorta is roughly 5 cm^2, Capillary is 30 um^2, but there are 30 billion.
  - Thus the cross-sectional area of the capillaries is 3000 cm^2.
- The same total blood flow of 5L/min passes each level.
  - As vessels branch off, blood velocity (cm/sec) steadily decreases.
- Capillaries have the slowest blood vel., the greatest surface area, and shortest diffusion distance.
- Trends then reverse as the blood vessels begin to increase in size.

Pressure and Resistance Throughout Systemic Circulation
- Fall in blood pressure is proportional to resistance (slope).
- Total Peripheral Resistance (TPR) = total resistance throughout entire systemic circulation.
  - 50% of TPR is in arterioles.
  - 20% in aorta and arteries.
  - 20% in capillaries.
  - 10% in veins.

Q: Pressure and Resistance Throughout Systemic Circulation
- Aorta and Large Arteries:
  - Very [...] resistance to blood flow, pressure remains [...].
A: little; high

Q: Pressure and Resistance Throughout Systemic Circulation
- Small arteries:
  - [...] in pressure begins, as resistance inc.
A: Fall

Q: Pressure and Resistance Throughout Systemic Circulation
- Arterioles:
  - Greatest resistance to flow accounting for about [...] the resistance of the entire systemic circulation.
A: half

Q: Pressure and Resistance Throughout Systemic Circulation
- Capillaries:
  - Pressure drop of [...] mmHg.
A: 20

Q: Pressure and Resistance Throughout Systemic Circulation
- Venous Circulation:
  - By the time blood reaches the right atrium, pressure approaches [...].
  - [...] ensure no backflow.
A: 0; Valves

Pressure and Resistance throughout Pulmonary Circulation
- Low pressure-low resistance circuit.
  - Left side of the heart has to generate higher pressure.
- Pulmonary artery = 15 mmHg, capillaries = 8, left atrium = 5.

Q: Pulse Pressure: [...].
At rest: [...] mmHg
A: Difference between systolic and diastolic pressure; 40

- Pulse pressure is influenced by two main factors:
1. Stroke volume.
- The greater the stroke volume, the greater the pressure increase in systole and decrease during diastole (inc. pulse pressure).
1. Compliance (stretchability of the blood vessels in the arterial system).
- The greater the compliance of the arterial system, the less the rise the pressure for a given stroke volume.
- This dampening of the pressure output from the left ventricle is called the Windkessel effect.
- Age and atherosclerosis stop elasticity and result in higher bp.

Mean arterial pressure (MAP) is defined as the average pressure throughout the entire cardiac cycle.
  - Slightly less than the average between systolic and diastolic pressures (duration of systole is shorter than diastole).
- MAP = Diastolic pressure + ⅓ Pulse pressure
  - = ⅔ Diastolic pressure + ⅓ Systolic pressure = 93 mmHg at rest.
- MAP = Cardiac Output x Total Peripheral Resistance

Q: [...] (RPP)
- Way to measure the workload of the heart.
- RPP = [...] x [...].
A: Rate Pressure Product; systolic pressure; heart rate

Pressure, Flow and Resistance
- A segment of high resistance makes the pressure before the kink go up and the pressure after very low, this is what is happening in the resistance vessels (arterioles).

Q: Blood flow
- Blood travelling by the vessel wall goes [...] than the center.
Q = [...]/[...],
A: slower; (P1 - P2); R

Q: Resistance = [...]
- Resistance is directly proportional to the length of the vessel and the viscosity of the fluid, but inversely proportional to the [...] power of the radius.
A: 8Ln/(pi*r4); 4th

Poiseuille-Hagen Equation

Further Derivation
- Note, in the short term, viscosity of the fluid and the length of the blood vessels do not change.
  - This can change with certain things such as EPO, which increases RBC’s and thus blood viscosity, combining with dehydration to be dangerous.
- Combined with the original flow equation, results in Q = deltaP*r4.

Q: Why does a Parallel Circuit help with resistance?
1. You can control the [...] of parallel vascular beds independently, altering the blood flow through each to a different extent.
2. There is also relatively low resistance since there is not one long pathway, which would require a [...] blood pressure to generate the same Q, dec. heart workload.
A: resistance; higher

Blood Vessel Structure
- The walls of arteries and veins contain three layers:
  - Outer layer (tunica externa)
    - Fibrous connective tissue
  - Middle layer (tunica media)
    - Smooth muscle and elastic tissue
  - Inner layer (tunica interna)
    - Endothelial cells.
  - Veins also contain valves
- Capillaries are essentially just one layer of endothelial cells.

Relative Amounts
- Aorta is very thin walled but elastic.
- Arterioles are small with thick walls.
  - Have a lot of muscle.
  - High resistance, do not expand, resulting in a huge drop in blood pressure.
- Veins are very large, with thin walls, and a little bit of elasticity, since they contain 70% of the total blood volume.
  - Also contain smooth muscle to increase constriction for venous return, EDV and CO.
- Artery has thicker walls than the vein, aorta is more elastic than vena cava etc.

Q: An important function of the cardiovascular system is to maintain [...], ensuring adequate blood flow in the system.
A: mean arterial pressure

Q: [...]: [...] X [...]
A: Mean Arterial Pressure; CO; TPR

Q: [...]: [...] X [...]
A: CO; HR; Stroke Volume

Q: Blood Flow (most simplified equation) = [...] x [...]
A: Pressure Difference; r^4

Q: 3 mechanisms of controlling blood flow
Local Mechanisms (by the [...])
Humoral Mechanisms (by [...])
Neural Mechanisms (by [...])
A: tissue; substances in the blood; ANS

Q: Autoregulation (Local Control) of blood flow
- A method of maintaining constant [...] at different pressures.
A: blood flow

Autoregulation (Local Control) of blood flow
- Myogenic Theory (Bayliss Effect)
- An increase in BP causes a dilation of the arteriole, followed by a reflexive constriction, protecting the blood vessels.
- Essentially you maintain blood flow at a higher bp by decreasing radius.

Myogenic Theory (Bayliss effect) relies on stretch activated cation channels being opened, depolarizing the cell and activating calcium channels to contract the muscle and increase resistance compared to nomal.
- Note: This essentially functions by creating a kink in the artery, dropping bp in the capillaries after.

Q: Metabolic Theory of Local Control
[...] (constriction or dilation) may occur due to the presence or absence of [...] in arterioles.
A: Vasomotion; vasodilator metabolites (VDMs)

Metabolic Theory of Local Control
VDMs (dilators) include
1) Lack of O2.
2) [H+]
3) CO2
4) Temperature
5) [K]o
6) [adenosine] (from ATP breakdown).
- Dilates everything but the kidney
7) Lactic acid

Q: Metabolic Theory of Local Control
If blood pressure gets too [...], it will wash away the VDMs resulting in [...] of the arteriole and [...] blood flow.
A: high; constriction; decreasing

Q: Metabolic Theory of Local Control
Reactive Hyperemia
Brief [...] in blood flow following a period of arterial blockage, such as after a tourniquet.
- [...] build up, resulting in a drastic [...] in blood flow.
A: increase; VDMs; increase

Q: The [...] theory is the strongest regulator of blood flow during exercise.
A: metabolic

Q: Humoral Regulation of Blood Flow
- Vasoconstrictor agents [...] blood flow, [...] MAP (resistance).
A: decrease; increase

Q: Humoral Regulation of Blood Flow
- Vasodilator agents [...] blood flow, [...] MAP (resistance).
A: increase; decrease

Q: Humoral Regulation of Blood Flow
[...] causes vasoconstriction and vasodilation depending on the receptor it attaches to.
- Alpha [...], beta2 [...]
A: Epinephrine; constricts; dilates
Extra: ACBD (Ie ACDC meme)

Humoral Regulation of Blood Flow
Epinephrine is secreted by the adrenal medulla and constricts blood vessels when it binds to a1 adrenergic receptors.
Extra: ACBD (Ie ACDC meme)

Q: Humoral Regulation of Blood Flow
[...] is secreted when there is a drop in blood pressure and/or a drop in [...].
A: Renin; Na+

Q: One way to fix [...] is to take an ACE inhibitor.
A: hypertension

Humoral Regulation of Blood Flow
Vasopressin is secreted by the hypothalamus and promotes water reabsorption in the kidney.
- In high concentrations, it also directly produces vasoconstriction

Humoral Regulation of Blood Flow
Endothelins (ETs) are found in endothelial cells and are released when blood vessels are crushed to reduce blood loss by constricting blood vessels.

Humoral Regulation of Blood Flow
Epinephrine may dilate blood vessels when it binds to b2 adrenergic receptors.
- This occurs in skeletal and cardiac muscle, as well as the liver!
- Also note, different to B1 in heart.

Q: Humoral Regulation of Blood Flow
[...] is formed in the body fluids, and [...] (released by damaged tissue) [...] blood vessels.
A: Bradykinin; histamines; dilate

Humoral Regulation of Blood Flow
Nitrous Oxide, also known as endothelial derived relaxing factor (EDRF) results in dilation of blood vessels.
- Nitroglycerin is used to treat angina pectoris (chest pain).
- Works by releasing cGMP, which relaxes the muscles, increasing blood flow.
- VIAGRA

Q: Humoral Regulation of Blood Flow
Prostaglandins result in [...] of blood vessels.
A: dilation

Q: Humoral Regulation of Blood Flow
Atrial Natriuretic Factor (ANF) is released by [...] when they are stretched and [...] blood vessels.
A: atrial muscles; dilates

Q: Neural Control Mechanisms (ANS)
- SNS vasoconstrictor fibers: Release norepinephrine, which binds to [...] adrenergic receptors, causing [...].
A: a1; vasoconstriction

Q: Neural Control Mechanisms (ANS)
- Sympathetic cholinergic vasodilator fibers: Release Ach, which binds to [...] receptors in [...] muscle blood vessels, causing [...].
- Might not be found in humans.
A: muscarinic; skeletal; vasodilation

Q: Neural Control Mechanisms (ANS)
- [...] has no direct effect on blood vessels, rather it is the absence of SNS activity.
A: PNS

Q: Neural Control Mechanisms (ANS)
- Overall, is capable of adjusting both peripheral resistance and cardiac output, in order to maintain [...].
A: MAP

Q: Neural Control Mechanisms (ANS)
- In general, Ach causes [...] and epi/norep cause [...].
A: vasodilation; vasoconstriction

Q: [...] in active tissue will block vasoconstriction, even if ANS is pushing for constriction.
A: VDMs

Q: Norepinephrine does not bind to [...] adrenergic receptors, thus won't cause [...]
A: b2; vasodilation

Q: Baroreceptor reflex is a [...] feedback mechanism which adjusts both [...] and [...] to maintain a certain MAP.
A: negative; cardiac output; TPR

Q: Low Pressure Volume Receptors
- Not involved in the baroreceptor reflex.
- Located primarily in the [...] atrium.
- Detect [...] of circulation, helping regulate [...].
A: right; fullness; blood volume

Q: Low Pressure Volume Receptors
- A drop in blood volume causes the release of [...] to help retain water, as well as [...] at high concentrations.
A: ADH; vasoconstriction

Q: Low Pressure Volume Receptors
- A rise in blood volume causes the release of [...] to [...] blood vessels, as well as less release of [...], to produce more urine.
A: Atrial Natriuretic Factor; dilate; ADH

Q: High Pressure Baroreceptors
- Located in the walls of the [...] as well as the [...].
A: aorta; carotid sinus

Q: High Pressure Baroreceptors
- Monitor the [...] of blood vessels, signalling to the CV centre if it becomes too high.
A: stretch

Q: High Pressure Baroreceptors
- Afferent fibers from the baroreceptors travel up to the [...], which is the location of the CV centre.
A: medulla

Q: Baroreceptor Reflex
- [...] fibers from the medulla travel down to the [...].
A: PNS; SA/AV nodes

Baroreceptor Reflex
- SNS fibers from the medulla go down to the spinal cord, where they then synapse and travel to the SA and AV nodes as well ventricular muscle and the arterioles and veins.

Q: CV Centre
- The [...] [...] all afferent baroreceptor information.
A: solitary tract nucleus (NTS); receives

Q: CV Centre
- The [...] sends all [...] signals from the centre.
A: vagal center; PNS

Q: CV Centre
- The [...] sends all [...] signals from the centre.
A: vasomotor centre; SNS

Q: CV Centre
- There is an [...] interneuron between the NTS and the [...]
- Ie, Lots of APs activates a [...] nervous system response.
A: excitatory; vagal centre; parasympathetic

Q: CV Centre
- There is an [...] interneuron between the NTS and the [...]
- Ie, Lots of APs deactivates a [...] nervous system response.
A: inhibitory; vasomotor center; sympathetic

Q: Recall, the limbic system is very important for behavioural responses such as [...]
A: fight or flight

Q: The hypothalamus exerts control over the CV center, which is in the [...]
A: brainstem

Q: CV Regulation during emotional stress
- Inc. activity of sympathetic [...] vasodilators to muscle arterioles.
A: cholinergic

Q: CV Regulation during emotional stress
- Inc. activity of sympathetic cholinergic fibers to [...], to produce sweat.
A: sweat glands

Q: CV Regulation during emotional stress
- Inc. activity of sympathetic cholinergic fibers to [...], to produce epinephrine ([...] skeletal muscle arterioles and [...] kidney, intestine arterioles).
A: adrenal medulla; dilates; constricts

Q: CV Regulation during emotional stress
- Inc. constriction in the intestines and [...].
A: kidney

Q: CV Regulation during emotional stress
- Inc. constriction in the [...] to increase EDV.
A: veins

Q: CV Regulation during emotional stress
- Dec. activity of vagal nerve and inc. in sympathetic signals to the heart, inc heart rate and [...].
A: contractility

Q: CV Regulation during exercise
- Local: [...] are responsible for dilating arterioles in the [...], as well as [...] vasoconstrictor effects from SNS in those same arterioles.
A: VDMs; skeletal muscle; blocking

Q: CV Regulation during exercise
- Mechanical: [...] inc. venous return and all the blood flow things.
A: Muscle pump

Q: CV Regulation during exercise
- Nervous System: Sympathetic signals constrict arterioles in the [...] and [...] HR and SV in the heart.
A: kidney; inc.

Q: CV Regulation during exercise
- Nervous System: Increase in body temperature causes the hypothalamus to [...] vasoconstriction signals from sympathetic outflow at the skin, and [...] sweating.
A: inhibit; inc.

Q: CV Regulation during exercise
- Humoural: If exercise is intense enough, [...] releases epinephrine, which enhances [...], constricts or dilatess blood vessels.
A: adrenal medulla; HR and contractility

Q: Functions of the Kidney
1. Regulation of [...] composition of blood.
A: ionic

Q: Functions of the Kidney
2. Regulation of blood [...].
- Should be around [...]
A: pH; 7.2

Q: Functions of the Kidney
3. Regulation of blood [...].
- Modified by excreting or conserving [...].
A: volume; urine

Q: Functions of the Kidney
4. Regulation of blood pressure.
- Modified by excreting or conserving [...].
A: urine

Q: Functions of the Kidney
5. Maintenance of [...] of the blood.
- Should be roughly [...]
A: osmolarity; 300

Q: Functions of the Kidney
6. Production of [...].
- [...] (inc. RBC) as well as activated Vitamin D (aka [...])
A: hormones; EPO; calcitrol

Q: Functions of the Kidney
7. Production of [...] through [...].
A: glucose; gluconeogenesis

Side Function of the Kidney
- Excretion of wastes such as urea (from AA), uric acid (nucleotides), creatinine (from creatine) and urobilin (hemoglobin)

Q: The renal [...] functions to filter the blood into a fluid called [...].
A: corpuscle; filtrate

Q: The [...] gets the most blood out of any organ, but if mass is taken into account, the [...] are by far the highest.
A: liver; kidneys

Q: The pores in the bowman's capsule are called [...].
A: fenestrations

Q: [...] are finger-like projections in the bowman's capsule, filtrate travels [...] them into the lumen.
A: Podocytes; in between

Q: The [...] is -[...] charged and binds endothelial cells to the [...].
A: basal lamina; vely; podocytes

Q: RBCs and WBCs are not found in urine because [...].
A: they are too large

Q: Proteins are not found in urine because [...] or [...] (repelled by basal lamina).
A: they are too large; they are -vely charged

Q: -ve ions are found in the urine because they are [...]
A: small

Q: You can lose the function of one of your two [...] and still live a normal life.
A: kidneys

Q: The kidneys are in between the membranes which line the [...] and the [...] of the back.
A: abdomen; bones/muscle

Q: Each kidney has [...] nephrons.
A: 1 million

Q: Each nephron is made up of a [...] and the [...].
A: renal corpuscle; tubule

Q: Each renal corpuscle is made up of a [...] and the [...].
A: bowman's capsule; glomerulus

Q: Bowman's Capsule is a fluid filled hollow ball which surrounds the [...].
A: glomerulus

Q: Bowman's Capsule is mainly made up of [...] epithelial cells.
A: squamous

Q: The glomerulus is the actual [...] which filters filtrate into the bowman's [...] space.
A: capillary bed; capsular

Q: In order to for a substance to filter into the bowmans capsule, it must go through the [...], then the [...] and finally inbetween the [...].
A: fenestrations; ECM sieve; podocytes

Q: The tubule of the kidney is made up of [...] layer(s) of epithelial cells.
- The [...] they express determine which solutes they filter.
A: one; transporters

Q: The first part of the tubule is the [...], which has many [...] to increase SA, and can reabsorb many ions and water.
A: proximal convoluted tubule; microvilli

Q: The second part of the tubule is the [...], which doesn't have many [...] and doesn't absorb much.
- Tight junctions ensure that anything reabsorbed must go through [...].
A: descending loop of henle; microvilli; cell membrane

Q: The third part of the tubule is the [...], has a small section with [...] cells which reabsorb ions, this absorption can occur [...] cells.
A: ascending loop of henle; thick; between

Q: The fourth part of the tubule is the [...], which absorbs many ions, but only [...] the cells.
A: distal convoluted tubule; through

The fifth part of the tubule is the collecting duct, which has two types of cells:
1) Principle cells: Respond to hormones and adjust sodium/water reabsorption.
- Has short microvilli.
2) Intercalated cells: Respond to pH changes and adjust acid/base excretion into filtrate.
- Has long microvilli, in both type A/B cells.
- All cells are tightly adhered, preventing paracellular reabsorption.

Q: Only the [...] and [...] allow paracellular transport in the kidney.
A: PCT; ascending loop of henle

Q: The Kidney has an afferent and efferent [...], which is interesting since that means you can control blood flow in and out of the [...]
A: arteriole; capillary bed

Q: The [...] apparatus is the part of the [...] which wraps past the corpuscle in between the two arterioles.
A: Juxtaglomerular; ascending loop of henle

Q: [...] cells are in the juxtaglomerular apparatus and are sensitive to filtrate composition, signalling to modify the diameter of the [...] arteriole, or to the [...] cells
A: Macula densa; afferent; juxtraglomerular/granular

Cortical nephrons compose 80% of the nephrons in humans and are located relatively shallow in the kidney.
- Surrounded by pertitubular capillaries.

Juxtamedullary neurons compose 20% of the nephrons in humans and are located relatively deep in the kidney.
- Surrounded by straight vasa recta capillaries.
- Key in creating very concentrated urine, so they are more prominent in desert animals.

Q: 50 mL/min is considered a [...] GFR
A: low

Q: Leukocytes [should/should not] be found in the urine, because they are [...].
- If found, can signal a [...]
A: should not; too large; UTI

Q: Nitrites [should/should not] be found in the urine, because they are [...].
- If found, can signal a [...]
A: should not; nitrates converted into nitrites by bacteria; UTI

Q: Proteins [should/should not] be found in the urine, because they are [...] and also [...].
A: should not; too large; -ve

Q: Bilirubin [should/should not] be found in the urine.
- If found, can signal [...]
A: should not; liver failure

Q: Glucose [should/should not] be found in the urine.
- If found, can signal [...], which is normally filtered but [...].
A: should not; diabetes; reabsorbed

Ketones should not be found in the urine.
- If found, can signal ketoacidosis, which may be caused by a ketogenic diet and the breakdown of fats

Q: Blood [should/should not] be found in the urine.
- If found, can signal [...]
A: should not; UTI

Q: Urine has a pH of [...]
A: 6

Specific gravity is the density of urine compared to the density of water.
- Takes into account the size and number of particles.
-- 50 mOsm to 1400 mOsm molarity

Fenestrations can be found in the glomerulus, spleen, intestines and endocrine glands.

Q: Granular cells release [...]
A: renin

Bilirubin Metabolism
- RBC (hemoglobin) is broken down in the spleen into heme and then bilirubin which is transported in the blood by albumin to the liver, where it is converted into conjugated bilirubin.

Bilirubin Metabolism
- Conjugated bilirubin is converted in the intestines to urobiligen by bacteria, and then either excreted in the poo or taken into the blood and excreted through the urine.

Q: Bilirubin Metabolism
- Urobiligen in the urine should not be too [...] or [...]
A: high; low

Q: The cells in the tubules which are highly absorptive rely on many [...] for their energy for transportation (active and secondary)
A: mitocondria

Stages of Renal Disease
- 180 L/day aka 125 mL/min of filtration is normal and healthy.
- Any higher and your nephrons may burst which is an issue since they cannot be regenerated.
- Any lower and waste products can build up.

Stages of Renal Disease
- GFR (glomerular filtration rate) can be a cause for concern if it is less than 90 mL/min.
- In stage 2, GFR is from 60-89 mL/min.
- Stage 3 is 30-59 mL/min.
- Stage 4 is 15-29 mL/min.
- Stage 5 (dialysis machine is required) has is less than 15.

Q: Autoregulation of GFR
- The kidneys always filter the same amount of blood regardless of the [...], to do this they use a [...] response as well as [...] feedback.
A: blood pressure; myogenic; tubuloglomerular

Autoregulation of GFR
- The myogenic response involves an inc. in bp resulting in a stretch of the afferent arteriole, and a successive responsive vasoconstriction which results in a drop in bp in the glomerulus.

Q: GFR Regulation by Renal Blood Flow
- [...] arteriole constriction results in a [...] in blood pressure in the glomerulus.
A: Afferent; drop

Q: GFR Regulation by Renal Blood Flow
- [...] arteriole constriction results in a [...] in blood pressure in the glomerulus.
A: Efferent; rise

GFR Regulation by Renal Blood Flow
- Angiotensin II results in the contraction of both arterioles and a dec in bp in the glomerulus.
- Less filtration than normal.

Q: The [...] and [...] both have many simple squamous cells.
A: bowman's capsule; descending loop of henle

Q: Filtration Coefficient
- The net [...] is the most important contributor to GFR, but the [...] available, and the [...] (not changed on purpose) of barriers also contribute.
A: filtration pressure; SA; permability

Q: Filtration Coefficient
- The space between [...] can increase, resulting in a greater [...] of filtration.
A: podocytes; volume

Q: Filtration Coefficient
- The [...] of the basal lamina (not changed on purpose) can increase to allow [...] to filter into the filtrate, but does not change [...].
A: permeability; small proteins; volume

Filtration Coefficient
- An increase in the size of fenestrations would result in more RBCs/proteins being found in the filtrate!
- Although they would also have to go through the basal lamina and podocyte barriers.

Q: Staghorn kidney stones are super [...] and [...] be urinated out.
A: large; cannot

Q: Net Filtration Equation
- If net filtration is higher than 10 mmHg, you have [...] filtration.
A: more

Net Filtration Equation
- Hydrostatic pressure of the glomerulus is the most important pressure in the system and causes more filtration
- Can be altered by vasoconstriction/dilation of the arterioles.

Q: Net Filtration Equation
- [...] causes [...] filtration
- If someone has kidney stones, this pressure goes [...], because there is more fluid.
A: Hydrostatic pressure of the bowman's capsule; less; up

Net Filtration Equation
- Colloid osmotic pressure of the bowman's capsule causes more filtration. If there is protein in the bowman's capsule, water is brought in to equilibriate the concentration.
- May seem like a good idea, but you do not have protein in the filtrate, and it would cause too much filtration.

Net Filtration Equation
- Colloid osmotic pressure of the glomerulus causes less filtration.
- There is a lot of protein in the blood of the glomerulus.

Q: Net Filtration Equation
- Net filtration = [...]
A: (Pgc + πbc) - (Pbc + πgc)

Q: Filtration is the process through [...].
A: fluid is filtered from glomerulus into bowman's capsule

Q: Reabsorption is the process through [...].
A: solutes or fluid are reabsorbed back into the blood

Q: Secretion is the process through [...].
A: solutes are selectively moved into the tubule

Q: Excretion is the process through [...].
A: waste is exerted as urine

Tubuloglomerular Feedback: If the GFR of a nephron increases, it will respond by reducing the GFR.
- Macula densa cells of JGA detect increase in fluid flow in ALoH and release a paracrine factor which vasoconstricts the afferent arteriole.

Q: GFR can be calculated through the formula Excretion = [...].
- If you use a substance which is not reabsorbed or secreted, then Excretion = [...], making it possible to calculate the GFR
- An example of a useful molecule is [...]
A: Filtration + Secretion - Reabsorption; Filtration; insulin

Q: [...] X = [...]
A: Filtered load of; [X]_plasmaxGFR

The PCT reabsorbs 65% of the water including solutes such as glucose, AAs, ions like Na, K,Cl and urea.

Q: The descending loop of henle reabsorbs [...] and some [...]
A: water; sodium

Q: The ascending loop of henle does not reabsorb [...] but does reabsorb many ions such as [...]
A: water; Na,K,Cl

Q: The loops of henle together reabsorb [...] of fluid
A: 20%

Q: The DCT and collecting duct together reabsorb [...] of fluid
A: 14%

The DCT functions like the ascending loop of henle and only reabsorbs ions such as Na,K,Cl as well as Ca (but only if you have PTH hormone).

The collecting duct can function to reabsorb water or sodium or secrete K and acid/base

Q: The basolateral membrane of renal epithelial cells faces the [...]
A: interstitial fluid

Q: Reabsorption can occur [...]cellularly or [...]cellularly
A: trans; para

Q: Secretion can only occur [...]cellularly
A: trans

Q: Note, the filtrate and interstitial fluid both have a [...] conc. of Na than the epithelial cells.
A: higher

Cl reabsorption is coupled with cation reabsorption to balance out the charge, but has its own issues because it is typically against its electric gradient when going into epithelial cells and its conc gradient when travelling into the interstitial fluid.

Q: Water is reabsorbed mainly [...]cellularly through [...].
A: trans; aquaporins

Q: Tubuloglomerular Feedback
- [...] cells have [...] to detect fluid motion, bending more if the fluid is flowing faster.
A: Macula densa; cilia

Tubuloglomerular Feedback
- IF CILIA BEND ALOT
- The cells release ATP which is broken down into adenosine and constricts the afferent arteriole.
- Notice, in the rest of the body, this causes dilation, but this is an exception.

Q: Tubuloglomerular Feedback
- IF CILIA BEND TOO LITTLE
- The cells release [...] which [...] the afferent arteriole.
A: nitrous oxide; dilates

Q: Tubuloglomerular Feedback
- The tubuloglomerular feedback response is [...] than the myogenic response.
A: slower

Creatinine is not reabsorbed and only slightly secreted, so it is a great choice for calculating GFR.
- Made from the breakdown of creatine in skeletal muscle.

Q: [...] = [...]
A: GFR; [creatinine]_urinex V_urine/day/[creatinine]_plasma

Q: GFR declines as you [...]
A: age

Q: The collecting duct increases reabsorption of [...] when [...] acts on the system.
A: water; ADH

Q: Glucose reabsorption depends on [...] which are only found in the PCT.
A: transporters

Q: The filtrate has a [...]x higher Na+ conc. than the tubule cells.
A: 30

Sodium Transporters in the Kidney
1. ENaC (aka the epithelial sodium channel).
2. Sodium symporters such as Na+/glucose.
3. Sodium exchangers such as Na+/H+.
4. Sodium/potassium ATPase.

Q: Chloride absorption into cells goes against the [...] gradient, but with the [...] gradient.
- Out of the cells into the interstitial fluid, it is the opposite.
A: electrical; concentration

Q: Water reabsorption in the kidney mainly occurs through [...] channels, of which, [...] are expressed in the kidneys.
A: aquaporin; 4

Q: Water reabsorption in the kidney can also occur paracellularly, but only in the [...].
A: PCT

Q: Proximal Tubule Explained
- Sodium/potassium ATPase on the [...] membrane, since both ions are travelling against their gradients.
A: basal

Q: Proximal Tubule Explained
- Sodium/glucose symporter is driven by the conc. gradient maintained by the [...].
A: Na/K ATPase

Q: Proximal Tubule Explained
- Sodium/AA symporter is also driven by the conc. gradient maintained by the [...], but there are {{c::20}} different AA transported!
A: Na/K ATPase

Q: Proximal Tubule Explained
- Paracellular transport depends on the [...] expressed.
A: claudins/occludins

Q: Proximal Tubule Explained
- [...] and [...] reabsorption follows the absorption of cations.
A: Water; chloride

Proximal Tubule Explained
- In diabetes, there is more glucose in the urine, saturating the sodium/glucose transporter, which means it cannot all be absorbed (note, only the PCT absorbs glucose).
- More glucose in the pee means more water, producing more pee.

Q: The descending loop of henle has [...] cells, which don't use a lot of [...].
A: simple squamous; energy

Q: Distal Convoluted Tubule Explained
Similar to the ascending limb, but there is no [...], instead using a [...] symporter.
There is also regulated transport of [...]
A: ion multiplier; sodium chloride; calcium

Ascending Loop of Henle
- NKCC2 absorbs one Na, 2 Cl and one K (notice, this is electroneutral!).

Q: Ascending Loop of Henle
- The NKCC2 is also expressed in [...] cells to measure conc. of ions.
A: macula densa

Q: Ascending Loop of Henle
- Paracellular transport only occurs in the [...] part, because there are better ways of using Na.
A: first

Q: Ascending Loop of Henle
- There is a channel in the basal membrane, which when [...] is high in the cell, it opens to let [...] out.
A: Cl; Cl

Q: Inc. uric acid in the blood is called [...]
A: hyperuricemia

Q: Inc. uric acid in the blood can cause both [...] (build up in [...]) and [...]
A: gout; joints; kidney stones

Q: Uric acid is formed from the breakdown of [...]
A: purines

Q: Uric acid is reabsorbed in the [...]
A: pct

Q: Any excess uric acid is [...] back into the tubule after [...]
A: secreted; reabsorption

The Principle Cells of the Collecting Duct
- Have two types of K channels:
RomK- which move in or out of the membrane depending on aldosterone.
BK- which is always in the membrane, and typically closed.

Q: Inc. aldosterone promotes [...] absorption and [...] secretion
A: Na; K

Angiotensin II has two main effects:
1) Inc. reabsorption of Na in the PCT
2) Vasocontriction of the afferent/efferent arteriole(s).

Angiotensin II binds to the AT1 receptor to engage its effects.
- If bound to the apical membrane, it increases action of the sodium/h exchanger.
- If bound to the basal membrane, it increases action of the sodium/potassium pump

Aldosterone increases reabsorption of Na in the principal cells
- Directly released in response to angiotensin II or high levels of K

Q: Aldosterone functions in the short term by bringing [...] channels to the membrane, or alternatively activating the [...]
A: na and k; sodium/potassium pump

Q: Atrial Natriuretic Peptide (ANP)
- Produced by [...] cells.
- [...] hormone.
- Released when stretch receptors detect [...] blood.
A: atrial; Peptide; increased

Q: Atrial Natriuretic Peptide (ANP)
- Functions to [...] sodium reabsorption:
1) Inhibits [...] release
2) Increases [...] (through vasodilation).
A: reduce; aldosterone; GFR

Renin Release
- Detection of low Na:
1) Baroreceptors
- Carotid sinus detects dec. BP
- JG cells are baroreceptors for the afferent arteriole.
2) Chemoreceptors
- Macula densa cells release prostaglandins.

Q: Renin Release
- Detection of low Na:
Note: Low sodium means less [...] so a lower BP.
A: water

Macula Densa Cells
- Detect Na through the activity of the NKCC2.
- When levels are too low, prostaglandins are released to promote renin release from JG cells.
- When levels are too high, adenosine is released, inhibiting JG cells.

Tubuloglomerular feedback
- Detect flow rate through the activity of the cilia.
- When levels are too low, prostaglandins and NO are released to promote renin release from JG cells.
- When levels are too high, adenosine is released, inhibiting JG cells.

Renal Paradox
- In high BP, ANP is released, causing vasodilation of afferent arteriole and increased Na excretion.
- But, macula densa cells release adenosine, causing vasoconstriction and decreased Na excretion.
- Recall, the kidney is trying to protect itself, while the body is trying to maintain homeostasis
- Thus, the effect from ANP is more important! You have net vasodilation.

Q: Potassium Handling
- Inc in K is called [...]
A: hyperkalemia

Q: Potassium Handling
- High K can trigger [...] release, promoting K [...]
A: aldosterone; secretion

Q: Potassium Handling
- High K can result from [...]
A: diet

Q: Diuresis: [...]
A: Increased production of urine

Q: Natriuresis: [...]
A: Increased excretion of sodium

Q: Diabetes Insipidus: [...] (neurogenic) or [...] (nephrogenic).
- Results in an [...] in urine volume.
A: Failure to release ADH; Failure to respond to ADH; inc

Q: Ethanol [...] ADH release, making you pee [...]
A: inhibits; more

ADH causes the translocation of aquaporins to the apical membrane in principal cells, promoting water reabsorption.

In the absence of ADH, the collecting duct is impervious to water.
- Pee is high volume, low concentration.

Q: By the end of the PCT, the osmolarity of the filtrate is [...]
A: 300

Q: By the end of the descending loop of henle, the osmolarity of the filtrate is [...]
A: 1400

Q: By the end of the ascending loop of henle, the osmolarity of the filtrate is [...]
A: 100

Q: The maximum difference between the inside and outside of the tubule that would still allow for transport of ions is [...] mosm.
A: 200

Q: ADH is released either when there is [...] blood volume or if there is [...] osmolarity (measured by [...] osmoreceptors in the hypothalamus).
A: low; high; shrinking

Q: What happens to ADH Release if you have high osmolarity and high bp?
- [...]
A: ADH is still released, because keeping osmolarity in check is more important than keeping the blood pressure low.

Q: What happens to ADH Release if you have low osmolarity and hemmoraging?
- [...]
A: ADH is still released, because the dec in blood volume is more important than the osmolarity here.

Q: Potassium Handling in the Collecting Duct
- Aldosterone causes [...] of K through translocated [...] channels.
A: secretion; RomK

Q: Potassium Handling in the Collecting Duct
- Normal sodium levels result in [...] filtrate flow, possibly opening the [...] channels, but not causing the translocation of [...]
A: faster; BK; RomK

Q: If the body is too acidic.
- Reabsorb [...]
- Excrete [...]
- Create new [...]
A: HCO3-; H+; HCO3-

Q: The [...] is responsible for conservation of bicarbonate.
A: PCT

Q: The [...] are responsible for fine proton or bicarbonate control.
A: intrercalated cells

Q: What is the consequence of an ACE inhibitor on bp?
A: Decreased Ang II, and subsequently decreased bp

Q: What is the effect of blocking NKCC2 on urine volume?
A: Inc. urine volume, because of decreased ion reabsorption, as well as a less concentrated interstitium further leading to less water absorption.

Q: What has a greater diuretic effect between blocking NCC or NKCC2?
A: Blocking NKCC2 because it carries more ions and is involved in medullary concentration, whereas NCC is not.
Thus your urine volume goes up more if you block NKCC2 vs NCC

Q: Why is an aldosterone blocker called potassium sparing diuretic?
A: Potassium is stopped from being secreted into the filtrate, but decreased reabsorption of na results in less absorption of water (more diuretic).

Q: [...] works by binding to the [...] receptor in the [...].
A: ADH; V2; collecting duct

Q: Type A Intercalated Cells
A: Excrete H+ and reabsorb HCO3-
Excrete H through H ATPase into lumen and H/K antiport on apical membrane.
Reabsorb HCO3- through HCO3-/Cl antiport on basal membrane

Q: Type B Intercalated Cell
A: Excrete HCO3- and reabsorb H+
Reabsorb H through H ATPase and H/K antiport on basal membrane.
Excrete HCO3- through HCO3-/Cl antiport on apical membrane

Bicarbonate Reabsorption
- In the PCT, most of the reabsorption of filtered bicarbonate occurs, but since there are no bicarbonate transporters on the apical membrane, CO2 and H20 are first absorbed.
- In the PCT, there is a sodium/bicarbonate symporter on the basal membrane which is responsible for reabsorbing bicarbonate.
- In this transporter, bicarbonate is the driver.

Q: One consequence of dealing with acidosis using type [...] intercalated cells, is the absorption of too much [...].
A: A; K+

Q: One consequence of dealing with alkilosis using type [...] intercalated cells, is the [...] of too much K+.
A: B; secretion

Q: Calcium Homeostasis
- [...] is the hormone which regulates calcium in the ECF.
A: PTH

Q: Calcium Homeostasis
- [...] is the hormone which regulates calcium absorption in the GI.
A: Calcitrol

Q: Calcium Homeostasis
- [...] of calcium is stored in the bones.
A: 99%

Q: Calcium Homeostasis
- Calcium is stored in the bone in the form of [...], which also serve to provide bone [...]
A: hydroxyapatite crystals; strength

Q: [...] bones are made through [...] ossification, which [...] require a cartilage template.
A: Long; endochondral; does

Q: [...] bones are made through [...] ossification, which [...] require a cartilage template.
A: Irregular; intramembraneous; does not

Endochondral Ossification
1. Mesenchymal cells condense into chondrocytes.
2. Chondrocytes release Type II collagen as well as proteoglycans.
3. Nutrients and oxygen begin to run out.

Endochondral Ossification
3. Nutrients and oxygen begin to run out.
4. Chondrocytes form hypertrophic chondrocyte cells.
5. Hypertrophic chondrocytes release type X collagen, as well as minerals-Calcium and phosphate which both function to strengthen the matrix.
6. VEGF is released to inc. angiogenesis and supply more nutrients

Endochondral Ossification
6. VEGF is released to inc. angiogenesis and supply more nutrients.
7. Hypertrophic chondrocytes begin to undergo apoptosis.
8. The cells are replaced by osteoclasts which degrade the matrix placed by the hypertrophic chondrocytes.
9. Osteoblasts replace the matrix with type I collagen as well as more minerals/hydroxyapatite, forming the final strong bone.

Q: Secondary ossification
- Same process as primary ossification, but occurs on the [...] of the bone, and after the fetus has been [...].
A: ends; born

Osteoarthritis
- Articular cartilage is persistent and should remain as type II collagen.
- If chondrocytes become hypertrophic and secrete type X collagen, the cartilage becomes more rigid and can tear/degrade.
- Only real option is to have a joint replacement

Q: Growth Plate
- The region between the [...] and the [...].
- AKA the [...]
A: primary ossification centre; secondary ossification centre; epiphyseal plate

Q: Growth Plate
- The chondrocytes in this region [...], then [...] into hypertrophic chondrocytes ([...] in size), which stretches out the growth plate, resulting in a longer bone.
A: proliferate; differentiate; larger

Q: Growth Plate
- If hypertrophy occurs too [...], the bone will not expand enough, or if chondrocytes are not [...]
A: soon; proliferative enough

Q: Growth Plate
- At the end of puberty, all chondrocytes have become [...] and undergone [...], being replaced by bone.
A: hypertrophic; apoptosis

Q: Angiotensin I is [...] AA and Angiotensin II is [...] AA
A: 10; 8

Angiotensin II acts in the PCT and serves multiple purposes.
1) It increases the activity of the na/K ATPase and Na/H exchanger.
2) Constricts both afferent and efferent arterioles
3) Releases aldosterone from adrenal medulla.

Aldosterone acts in the principal cells and serves multiple purposes.
1) It increases the activity of the na/K ATPase.
2) Increases the number of ROMK channels as well as Na channels in the membrane.

Q: ADH acts in the [...] and serves to
1) It increases the number of [...] channels in the [...] membrane.
A: principal cells; Aquaporin II; apical

Q: ANP acts to
1) Decrease [...] release
2) [...] the afferent arteriole.
A: aldosterone; Vasodilate

Q: [...] = [...]
A: % excretion; [ion]_urine[urine]_volume/Filtered load

Q: The [...] is the teacher which changes the strength of the [...] synapse in cerebellar learning.
A: climbing fibre; parallel/purkinje

Q: When you alter the world using glasses to the left, you will throw to the [...] to compensate.
A: right

Q: The [...] receptor, which is the receptor for [...] is on the [...] membrane.
A: V2; ADH; basal

Q: ANF decreases release of [...] as well as to an extent [...]
A: aldosterone; renin

Q: Aquaporin [...] are always in the [...] membrane of [...].
A: III/IV; basal; principal cells

Q: Aquaporin [...] is inserted into the [...] membrane of [...].
A: II; luminal; principal cells

Q: In Intercalated A Cells, there is a [...] as well as a [...] to get rid of H+.
A: potassium/H+ exchanger; H+ atpase

Q: The myogenic response [can/cannot] occur as both dilation and constriction in response to different bp changes.
A: can

Q: The skeletal muscle cholinergic exception is the only instance in which the SNS releases [...] onto [...], normally [...] is released.
A: Ach; blood vessels; norad

Q: Low pressure/volume receptors can detect [...] or [...] pressure/volume.
A: high; low

Q: [...] apparently [...] open [...] channels on the SR membrane.
A: Depolarization; cant; L-type Ca

Q: [...] as well as feedback from the [...] are both important to feed into the inferior olive for cerebellar learning.
A: Vision; muscles

Q: Caffeine blocks the [...] of [...] causing high HR and also [...] of the bladder.
A: actions; adenosine; contraction

Q: Ethanol blocks the [...] of [...]
A: release; ADH

Q: The cause of spasticity is essentially that the [...] is closer to [...]
A: rmp; threshold

Q: [...] are only found in primates, since they are responsible for fine finger manipulation.
A: Corticomotorneurons

Q: The output of the purkinje to the deep cerebellar nuclei is [...]
A: inhibitory

The dentate nucleus is more responsible for the distal limbs and red nucleus is more responsible for the proximal limbs

Q: Hemiballismus and huntingtons fundamentally are due to a [...] in the activation of the [...]
A: decrease; subthalamic nucleus

Q: 80% of the calcium is returned to the [...] by a [...]
A: SR; calcium ATPase

Q: Vagal tone refers to intrinsic [...] activity
A: PNS

Q: [...] channels are not affected by anything in the SA node, so the [...] stage is not affected by ANS stimulation.
A: L-type Ca; depolarizing

Q: 3 Ways EDV increases stroke volume
A: Higher Overlap
Greater troponin affinity for calcium
Opening stretch sensitive calcium channels

Q: Afterload lengthens stage [...] of the cardiac cycle and also reduces [...]
A: 2; stroke volume

Q: The resistance in the veins is [...] of TPR.
A: 10%

Q: Pulse pressure is affected by [...] as well as [...]
A: stroke volume; compliance

Q: RPP = [...]
A: systolic pressurexHR

Q: Temperature is a vaso[...]
A: dilator

Q: The [...] theory is the strongest determinate of blood flow during exercise.
A: metabolic

Q: High pressure baroreceptors have a [...] firing rate which [...] at higher pressures.
A: tonic; increases

Low pressure volume receptors
- At high pressures, ANF is released.
- At low pressures, ADH is released.

Q: In the baroreceptor reflex, the PNS [does/doesnot] innervate the ventricular muscle.
A: does not

Q: Remember, in the baroreceptor reflex, both an [...] in PNS and a [...] in SNS are important!
A: increase; decrease

Q: In the fight or flight response, you have [...] SNS output to the [...] (intestinal) arteries, which causes vaso[...]
A: increased; splanchinic; constriction

Q: [...] SNS stimulation of skin blood vessels is important to cool off.
A: Inhibiting

Q: Filtered load is merely the amount [...]
A: filtered

PCT ALL TRANSPORTERS

Descending Loop of Henle ALL Transporters

Ascending Loop of Henle ALL Transporters

DCT ALL Transporters

Principal Cells Transporters

Q: [...] is the actual enzyme which is activated by ADH.
A: Adenylyl Cyclase

Q: Low Na in the filtrate would make the kidney [...] the afferent arteriole.
A: dilate

Angiotensin II works via 4 mechanisms
1) Increasing the activity of Na/H exchanger
2) Increasing the activity of Na/K ATPase
3) Releasing Aldosterone
4) Constriction of the afferent/efferent arterioles, decreasing filtered load and increasing reabsorption

Q: Angiotensin II [...] ROMK translocation
A: inhibits

Aldosterone works by several mechanisms
1) Increasing Na channels
2) Increasing ROMK channels
3) Increasing activity of Na/K ATPase
4) Increasing expression of Na channel
5) Increasing expression of Na/K ATPase

Q: Maximum renin release occurs if there are three things happening
1) [...]
2) [...]
3) [...]
A: Low BP in kidney; Low BP in carotid sinus; Low Na in kidney

Q: The Na/HCO3 symporter is found in the [...]
A: PCT

Q: [...]ventilation causes [...]
A: Hypo; acidosis

Q: [...]ventilation causes [...]
A: Hyper; alkilosis

Q: Excessive [...] or [...] consumption can cause [...]
A: fat/AA metabolism; aspirin; acidosis

Q: Excessive [...] consumption can cause [...]
A: antacid; alkilosis

Q: The brain uses [...] blood than the inactive skeletal muscle
A: less

Q: Baroreceptors detect [...] not volume.
A: pressure

Q: ADH can also be called by another 3 letter name: [...]
A: AVP