Learning Objectives Flashcards by Katy Jensen

Discuss the homeostatic role of the cardiovascular system.

Main transport system for integrating homeostasis
Our body needs a circulatory system because diffusion would be too slow and inefficient in large, multi cellular organism
- “4 miles from center of body to skin surface”
- Every cell within 0.1mm of a capillary
Integration with other systems
- GI: nutrient
- Respiratory: O2/CO2
- Renal/GI: Wastes
- Skin/Muscles: Temperature
- Endocrine: Hormones
- Hematologic: Clotting factors
- Body Defense: Inflammatory mediators

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Distinguish between the pulmonary and systemic circulatory systems, and list the important consequences of the parallel arrangement of organs in the systemic circulation.

The heart is a dual pump: meaning the right and left sides are doing the exact same thing at the exact same time, atria and ventricle contract at same time.
Pulmonary circuit: RV to lungs to LA, one target
Systemic circuit: LV through aorta to RA, any vascular bed
Wall thickness: greater on left than right
- LV needs to provide more pressure to feed all organ systems
Cardiac Output from left and right are the same ~5L
Parallel arrangement: Blood can flow through one vascular bed and return to the heart (contrast to series)
- Equal access to good quality blood
- Takes less pressure than if arranged in series
- Allows for independent regulation of blood flow to each tissue

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Describe in both qualitative and mathematical terms the hemodynamic factors that determine blood flow, blood pressure, and resistance to blood flow, and list the variables that are most relevant in cardiovascular regulation.

Pressure, flow and hemodynamics: F=change in P/R
- F: Flow (L/min)
- change in P: Pressure difference between any two points
- R: Resistance to flow
- ***pressure gradient that determine flow, NOT absolute pressure*****
Resistance: R=8Ln/πr⁴
- L: vessel length, much greater in systemic than pulmonary circuit
- n: viscosity of fluid (blood), % Hematocrit
- r: radius of vessel, most important factor
  - smaller radius means more contact with vessel walls and increase resistance

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Briefly describe the functions of the four heart chambers.

Blood Flow
- Right Artium
- AV triucuspid valve
- Right Ventricle
- Pulmonary Semilunar valve
- Pulmonary System
- Left Atrium
- AV bicuspid valve
- Left ventricle
- Aortic Semilunar valve
- Systemic System
Valves
- open and close due to changes in pressure
- keep unidirection blood flow

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Identify the pressure gradients across all cardiac valves, and explain when valves are open or closed.

4 phases of the heart reference by left ventricle

Ventricular filing: DIASTOLE
- AV valves open, higher pressure in atria than ventricle
- “Atrial kick”: active contraction to push 10-20% more blood in to ventricle
- “End-Diastole Volume”: EDV, after ventricle filling, ~135mLs
Isovolumetric ventricular contraction: SYSTOLE
- 1st heart sound at start, AV valves close, LUB
- Ventricles contract, force development, pressure increases
- P atria < P ven < P in aorta and PA
- Volume constant at EDV
- ALL VALVES CLOSED: “isovolumetric”
Ventricular ejection: SYSTOLE
- eventually enough pressure builds up, P ven > P aorta and PA
- Seminlunar valves open, blood flows out of ventricle
- “Stroke volume”: SV, volume of blood ejected from each ventricle (same volume in each) at rest ~70mL
- “End-Systolic Volume”: ESV, volume blood remaining in ventricle after ejection
  - ESV = EDV - SV, 135mL-70mL ~ 65mls
Isovolumetric ventricular relaxation: DIASTOLE
- 2nd hear sound, SL valves close, DUP
- Volume is constant at ESV, all valves closed
- P atria < P ven < P aorta/PA

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Define the terms systole and diastole.

Mechanical events of the heart
Diastole: relaxation, last 2/3 of the cycle, filling with blood
Systole: contraction, lasts 1/3 of the cycle, blood being ejected

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Explain the phases of the cardiac cycle in terms of atrioventricular pressure changes.

Ventricular filing: DIASTOLE
- AV valves open, higher pressure in atria than ventricle
Isovolumetric ventricular contraction: SYSTOLE
- P atria < P ven < P in aorta and PA
- All valves closed
Ventricular ejection: SYSTOLE
- SL valves open, higher pressure in aorta/PA
Isovolumetric ventricular relaxation: DIASTOLE
- P atria < P ven < P in aorta and PA
- All valves closed

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Describe the structure of the plasma membrane, and explain how the membrane functions as semi-permeable barrier.

Membrane is composed of a phospholipid bilayer
- hydrophobic tails form inner layer, hydrophilic heads face outwards to inner and extracellular environments
Both size and charge determine membrane permeability: based on passive properties without protein involvement
- small hydrophobic molecules: easily pass through
- small uncharged polar molecules: have ability to pass
- larger uncharged polar molecules: difficulty passing
- ions: cannot cross membrance

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Explain what a membrane potential is, and describe the development of membrane potentials.

separation of charges across the membrance, convention is to define potential INSIDE the cell with respects to outside
arise due to selective movement of ions across the lipid bilayer
- due to ion selective channels: down concentration gradients
- due to ion transporters: use energy to setup concentration gradients and to some extent membrane potential
i.e. Na+/K+ ATPase, maintains Na and K gradient
- each cycle, 3 Na out and 2 K in, hydrolyzes ATP to ADP
- contributes to resting membrane potential of 10mV
i.e. Selective pores: initially ions move down concentration gradient, this establishes a membrane potential (charge difference) that prevents any more molecules to move out at equilibrium

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Explain the use of the Nernst potential to determine the equilibrium potential of an ion.

Used to determine/calculate membrane potential of a given ion AT EQUILIBRIUM
E (K) = ( - R T / z F ) ln ( K_in / K_out )
- z: valence or charge of ion
- R and F: constants
- T: temperature
E (K) = - ( 60 mV ) log₁₀ ( K_in / K_out )
- **quicker to use** consider temp to be 30⁰K

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Describe basic structural features and physiologic roles of ion channels.

Structural features:
- Ion conducting pore: increased membrane permeabilty to certain ion
- Gates: part of channel that can open and close conducting pore
- Sensors: detectors of stimuli that respond to electrical potential changes or chemical signals, sensors couple to channel gates to control the probabilty that they open or close
Physiological Role:
- Electrical signals such as an AP and set up resting membrane potential
- Flux of ion contribute to volume regulation and polarized transport
- A few ions, notably Ca²⁺, make regulatory signals inside the cells, i.e. the heart

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Define action potential, and explain some of its common characteristics.

unitary electrical signal in cells, brief (<1/2 sec) but large voltage impulse (>70mV) which constitutes electrical signals in cells
differ in shape, magniture and duration
common features:
- all-or-nothing, trigger-like initiation, threshold
- initial phase always associated with large membrane depolarization
- AP is complete upon repolarization of membrane
- Refractory period of varying lengths

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Explain how sodium, calcium and potassium channels give rise to difference components of the cardiac muscle cell action potential.

Sodium Channels: open rapidly and immediately
- opening depolarizes membrane
- involved in initiating action potentials
Calcium Channels: open slowly and inactivate slowly
- opening depolarized membrane
- involved in initiating and/or prolonging the AP
Potassium Channels: open slowly
- opening repolarizes membrane
- involved in terminating action potentials

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Draw a typical cardiac muscle cell action potential, name the phases, and describe ion channel events that determine the shape.

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Explain the concepts of threshold and refractory period.

Threshold: potential at which AP is initiated 50% of the time
- ensure transmission of meaningful signals rather than random noise
- Na channels determine the threshold in cardiac muscle cells
- may be different under different circumstances
Refractory Period: period immediately following stimulation during which excitable cell is unresponsive to further stimulation
- mainly due to inactivation or unavailabilty of Na channels
- cannot have two action potentials on top of each other
- Absolute RP: regardless, another AP cannot be generated
- Relative RP: stronger than normal stimulus can induce AP

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Describe the general organization and function of the autonomic nervous system.

Three systems: sympathetic, parasympathetic, and enteric
Largely involuntary
Innervate everything except skeletal muscle
Controls visceral fuctions necessary for like
- i.e. cardiac output, blood flow, metabolis, GI motility, urogenital fn, body temp, sweating, endocrine gland secretions

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Contrast the general functions of the parasympathetic and sympathetic divisions of the autonomic nervous system.

Sympathetic:
- responses prepare the body for emergency or stressful situations
  - “FIGHT OR FLIGHT”
- activates process facilitating physical exertion and inhibits processes that do not help
- Diffuse/distributed
  - short preganglia nerve to sympathetic truck
  - long postganglia nerve with many targets
Parasympathetic:
- Day-to-day activities, quiet relaxed situations
  - “REST AND DIGEST”
- Activate processes that help during the resting state and inhibits processes that aid in physical exertion
- Discrete/directed
  - long preganglia neuron
  - short postganglia neuron, one target

Describe the role of the autonomic nervous system in the physiology of major organs.

Organs with dual innervation
- eye, heart, brochial tree, GI tract, salivary glands, urinary bladder, sex organs
Organ with single (SYMPATHETIC) innervation
- adrenal medulla, blood vessels, spleen, piloerector muscles, sweat glands
Organs with single (PARASYMPATHETIC) inervation
- lacrimal muscle (tear glands), ciliary muscles (in eye), sublingual salivary glands

Describe the distribution of cardiac sympathetic and parasympathetic (vagal) innervation of the heart (cardiac plexus).

Cardiac plexus: group of nerve ganglia located between the arch of the aorta and the bifurcation of the trachea
Sympathetic:
- from the sympathetic trunk: increase heart rate and cardiac contractility
Parasympathetic:
- from the vagus nerve (C10): decrease heart rate, only at level of atria not ventricles including SA and AV node

Explain that epinephrine and norepinephrine (catecholamines) are the major products produced in the adrenal medulla, and that their secretion can be influenced by stress, hypotension, and hypoglycemia.

considered to be hormones because release directly into blood stream
adrenal medulla: top hat on the kidney
- nodified sympathetic tissue
- inner layer produces epi and norepi
response to stress
- cortisol release from adrenal cortex
- epinephrine release from adrenal medulla
- sympathetic ganglion release norepinepherine

Explain the steps of catecholamine synthesis by tyrosine at an adrenergic synapse

tyrosine is taken into the presynaptic cell
- converted to dopa by tyosine hydroxylase
- then to dopamine which it transported into an intracellular vesicle
- inside it is NE (norepinephrine)
- vesicle fuses to plasma membrane at nerve terminal and content is release including NE
NE binds adrenoceptors on postsynaptic cell
to stop transmission
- NE difuses away from synaptic cleft
- taken up by presynaptic cell to be recycled

Explain the steps of acetylcholine biosynthesis at a cholinergic synapse.

choline take in to presynaptic cell
- binds with acetyl coenzyme A (synthesized in mitochondria)
- ChAT: choline acetyl transferase synthesizes ACh
- ACH is sequestered in intracellular vesicle
- vesicle fuses to plasma membrane at nerve terminal and content is release including ACh
ACh binds cholinoceptors to transmit signal
Acetylcholinesterase: breaks down ACh to stop response, choline is taken back up by presynatic cell

Explain peripheral organization and transmitters released by somatic and autonomic nervous systems.

Somatic NS: single neuron,
- ACh transmitter, synapses on skeletal muscle, NICOTINIC CHOLINERGIC RECEPTOR
Parasympathetic:
- long preganglionic neuron, synapses using ACh transmitter on postganglionic neuron, NICOTINIC CHOLINERGIC RECEPTOR
- short postganglionic neuron, synapses using ACh transmitter on smooth/cardiac/gland/etc., MUSCARINIC CHOLINERGIC RECEPTOR
Sympathetic:
- short preganglionic neuron, synapses using ACh transmitter on postganglionic neuron or adrenal medulla, NICOTINIC CHOLINERGIC RECEPTOR
- long postganglionic neuron, synapes using NE, ADRENERGIC RECEPTOR
- adrenal meulla releases epi or NE into bloodstream, ADRENERGIC RECEPTOR

Compare and contrast the different alpha and beta adrenergic receptors and their role in controlling different organs.

Adrenergic: Neurons that release NE, Epi, and DA
- most sympathetic pstganglionic, adrenal medulla
alpha isoform
1. smooth muscle (contracts smooth muscle, surrounding blood vessels)
2. vascular smooth muscle (contracts), platelets (aggregation)
beta isoform
1. heart (primarily form 1, increase HR, conduction velocity, and contractility), kidney (juxtaglomerular cells, increase renin release)
2. smooth muscle (eye/bronchioles/GI/urogenital/vascular, relaxes), heart (increase rate and contractility)
dopamine
1. vascular smooth muscle (especially renal vasculature, dilates blood vessels)
selectivity between Epi and NE
- Epi: beta-2 - vasodilation
  - extreme overload of epi binds alpha-1 - vasoconstriction
  - use for anaphylactic shock, cardiogenic shock, cardiac arrest
- NE: alpha-1 - vasoconstriction
  - use for sever hypotension and septic shock

Compare and contrast nicotinic and muscarinic acetylcholine receptors and their role in controlling different organs.

* cholinergic: neurons that release ACh * all motor neurons to skeletal muscle, all preganglionic ANS neurons, all postganglionic parasympathetic neurons * MUSCARINIC 1. automonic ganglia (some, depolarizes postsynaptic neurons slow EPSP) 2. heart (primarily atria, decrease HR and conduction velocity, contractility) axon terminals/autoreceptors 3. smooth muscle (eye/bronchioles/GI/urogenital contraction), secretory gland (increase secretion), vascular endothelium (increase NO release, dilates blood vessels) * NICOTINIC * N_m: neuromuscular junction (skeletal muscle contraction) * N_N:autonomic ganglia (typically, depolarizes postsynaptic neurons), arenal medulla (depolarizes medullary cells, leads to secretion of catecholamines)

Examples of ANS Actions on Lung Function

* Bronchial smooth muscle * M3 activation - muscle contraction - bronchoconstriction * Agonists: Methacholine (used to rule out asthma) * Antagonist (anti-cholinergics/anti-muscarinics): Ipratropium (SAMA) and Tiotropium (LAMA) - COPD treatment * Beta-2 activation - muscle relaxation - brochodilation * Agonists: Albuterol (SABA) inhaler, Salmeterol (LABA) * Antagonists (Beta-2 blockers): Propranolol

Examples of ANS Actions on Heart Function

* Parasympathetic response: M2 activation * bradycardia (decrease heart rate) via decreased slope of diastolic depolarization (phase 4 of SA node) * decrease AV node conductivity * decrease atrial contractility * Agonist: Methacholine * Antagonist: Atropine * Sympathetic response: Beta-1 and Beta-2 activation * Tachycardia via increase slope of diastolic depolarization * increase AV node automaticity and conductivity * increase HIS-Purkinje automaticity and conductivity * increase atrial and ventricular contractility * increase force and velocity of contraction, faster crossbridge formation * Agonist: Dobutamine (B1 specific) * Antagonist: Metoproplol (B1 specific

Examples of ANS Actions on Vascular Function

* M3 activation (endothelial cells) - vasodilation - decrease BP * alpha-1 and alpha-2 activation (smooth muscle cells) - constriction - increase BP * beta-2 activation (liver and skeletal muscle) - relaxation - decrease TPR - increase in blood flow to these tissues * D1 activation - dilation of renal arteries/arterioles - increase renal blood flow

Examples of ANS Actions on Kidney Function

* Beta-1 activation - stimulates renin relase from juxtaflomerular cells in kidneys - affects Na levels - BP changes