Human Phys unit 3 review

Smooth muscle found…

lines organs and glands

Smooth muscle consists of

circular and longitudinal layers

Smooth muscle contraction is

• involuntary

• layers alternate contraction (peristalsis = move food, fluid and urine throughout body) or contract together (same segment contracts circular and long ex. bladder)

What triggers smooth muscle contractions

varicosities

Single unit smooth muscle

• Some nerve innervation through gap junctions = coordinated contraction

• physical stretch (contraction) activates units (Ca2+ channels)

  • myogenic; Bayliss effect (ability of cells to dictate contraction based on what’s happening around) (vasculature, bladder, digestion)

• More synchronized across all units

Multi-unit smooth muscle

• Each unit is innervated by nerves = finer control

  • each individual cell has varicosities = individual activation

• ex. eyes, erector pili muscles

Smooth muscle has…

• no sarcomeres

• no troponin

• myosin binds to actin throughout filament = more dynamic = contraction in multiple directions

• tropomyosin (diff from skeletal)

• calponin

• caldesmon

• dense bodies (like tight junctions) connected to desmosomes (2 adjacent cells attached) = anchor cells together so whole sheet can as one unit

Smooth muscle contraction

1) Graded entry of Ca2+

2) Ca2+ binds to calmodulin

3) Active Ca2+-Calmodulin complex binds MLCK

4) Active MLCK phosphorylates the myosin light chain head via ATP

5) Phosphorylated myosin light chains head bind to actin and uses ATP to generate power stroke

Myosin ATPase in smooth muscle contraction is…

slower than in striated

• provides graded contractions = small slower contractions added together

• aids in maintenance of tension and lack of fatigue over longer periods of times

Smooth muscle relaxation

MLCP dephosphorylates myosin light chain (when in low concentrations of Ca2+)

Calcium stores for stimulating smooth muscle contraction

• Mechanoreceptive calcium channels = stretch causes them to open so calcium diffuses into cells

  • more stretch on muscle = more contract

• Sarcoplasmic reticulum = no DHP or ryanodine complex, more like GPCR IP3 pathway

Latch state

MLCP dephosphorylates myosin light chain when attached to actin —> generates and maintains tension with little hydrolysis of ATP

Relaxed state

MLCP dephosphorylates myosin light chain when myosin is not bound to actin

Cross bridge cycling

1. Active MLCK phosphorylates myosin light chain

2. myosin cross bridge attaches to actin

3. ADP and Pi release causes powerstroke

4. ATP binds to myosin causing release from actin

5. ATP is hydrolyzed to energize cross bridge

Smooth muscle GPCR pathways

• 1st messenger binds to GPCR —>

  • Activates PLC which cleaves PIP2 into IP3 and DAG —>

    • IP3 binds to sarcoplasmic reticulum and releases Ca2+ —>

    • Ca2+ binds to calmodulin, activating it —>

    • Active Ca2+-calmodulin binds and activates MLCK—>

    • MLCK phosphorylates MLC —> (continues to cross bridge cycling)

  • Activates Rho-kinase which phosphorylates MLCP —>

    • MLCP is inactive and can’t dephosphorylate MLC —> (continued cross bridge cycling)

• REDUNDANCY

Blood

• connective tissue

• 55% plasma

• 45% erythrocytes

• <1% Buffy coat (leukocytes and platelets

Functions of circulatory system

• transportation (ex. hormones)

• regulation (ex. body temp)

• protection (ex. antibodies, clotting factors)

Capillary network in loose areolar tissue

• small distance between capillaries to allow diffusion

• only 5% of blood at any one time in capillaries

Blood flow

blood flows from high to low pressure

resistance to blood flow depends on…

• Viscosity = how thick blood is

  • increase viscosity (thick) = increase resistance

• Vessel radius

  • decrease radius (vasoconstriction) = more resistance

  • most controlled

• Vessel length

  • increase length = increase resistance

  • increase with age and weight gain —> hypertension

Poiseuille’s law

resistance = 8 (viscosity) (length) / pi (radius^4)

** radius has most impact on resistance

Natural and Medicated ways that can Decrease Vascular Tone (Increase Vasodilation)

• Potassium channel openers: cause K+ to leave muscle —> hyperpolarization —> stop muscle contraction —> vasodilation

• L-type Ca2+ channel blockers: block calcium from entering —> prevent muscle contraction —> vasodilation and muscle relax

• Nitrodilators: increase vasodilation using nitric oxide

• Direct acting vasodilators = increase vasodilation (hydralazine, minoxidil)

• Alpha-adrenoceptor antagonist: blocks adrenaline and epinephrine from binding to adrenoceptors —> increase vasodilation

• Endothelin antagonist: block binding of endothelin —> prevents vasoconstriction

• Angiotensin receptor blocker: blocks angiotensin ii from binding to receptor —> prevents vasoconstriction

• Renin inhibitor and ace inhibitor: prevents formation of angiotensin ii (a vasoconstrictor) —> prevents vasoconstriction

Types of adrenoceptors

• Alpha 1

  • on smooth muscle of vasculature

  • bind epinephrine and norepinephrine —> increase IP3 —> increase Ca2+ from sarcoplasmic reticulum —> increased contraction —> vasoconstriction

  • low affinity = high concentration

• Alpha 2

  • on smooth muscle of vasculature and neurons

  • bind epinephrine and norepinephrine

    • on smooth muscle: decrease cAMP —> increased contraction —> vasoconstriction

      • **Function of cAMP

        • High [cAMP] inhibits MLCK —> decreased contraction

        • Low [cAMP] increases contraction

    • on sympathetic nerve: decrease Ca2+ release —> decrease norepinephrine or epinephrine release (negative feedback inhibition)

• Beta 1

  • only on heart

  • increase heart rate and myocardial contraction

  • High affinity = low concentration

• Beta 2

  • on smooth muscle of vasculature

  • binds epinephrine and norepinephrine —> increases cAMP —> inhibit MLCK —> increase relaxation —> vasodilation

  • High affinity = low concentration

Pericardial sack

fluid that surrounds heart

layers of heart

endocardium —> myocardium —> visceral pericardium —> pericardial cavity —> parietal pericardium

• myocardium is thickest = where most contraction is

Types of valves

• Atrioventricular valves (AV)

  • tricuspid (R)

  • bicuspid or mitral (L)

• Semilunar valves

  • pulmonary (R)

  • aortic (L)

**valves open and close based on pressure

• ex. high pressure in atria → AV open

• high pressure in ventricle → AV close

Types of circulation

Pulmonary circulation (right)

• Deoxygenated blood travels through vena cava → right atrium → tricuspid valve (AV) → right ventricle → pulmonary valve (semilunar) → pulmonary artery → lungs to pick up O2

• short distance

Systemic circulation (left)

• Oxygenated blood flows through pulmonary vein → left atrium → biscupid/mitral valve (AV) → left ventricle → aortic valve (semilunar) → aorta → tissues

• increased pressure because vessel is longer = more resistance

Heart muscle contraction is sync because

intercalated discs with gap junctions

Electrical conduction system in heart

Graded Potential travels through: SA node (primary control of heart contract) → internodal pathway (triggers contract in atria) → AV node → Bundle of His (where fibers connect to ventricles) → Purkinje fibers (innervates ventricles)

**ventricles contract slightly delayed from atria

Electrocardiograms

Measurement of depolarizations/repolarizations in the entire heart

• P wave = atrial excitation (depolarization)

• QRS wave = ventricular excitation (depolarization) - so large it masks the repolarization from atria relaxation

• T wave = ventricular relaxation (repolarization)

What part of the heart is the pacemaker

SA node

Automaticity of heartbeat

in absence of neural or hormonal control, depolarization will still occur in SA node (not that there isn’t any neural or hormonal control)

4 types of channels for pacemaker potential

• K+ channels

• Na+ funny type channels

• L-type Ca2+ channels

  • long type channels open longer

• T-type Ca2+ channels

  • transient channels that open briefly

Order of pacemaker potential channels

1. Na+ F-type channels open even when mem potential is below thresh → Na+ enters → some depolarization

2. T-type Ca2+ channels open → some Ca2+ enters → some depolarization

3. Threshold reached

4. L-type Ca2+ channels open → Ca2+ enters

5. full depolarization

6. K+ channels open and K+ exits

7. Repolarization

Channels that are actually causing pacemaker potential

Na+ F-type channels and Ca2+ T-type channels because they are needed to reach threshold

Why is Ca2+ faster at depolarization than Na+

2 ions instead of 1

Permeability of K+

gradual reduction from previous repolarization = slightly slower repolarization

Sympathetic system affects pacemaker potential/heartbeat

Affects Na+ F-type channels to increase Na+ permeability → quickens depolarization (not repolarization) → increases heart rate

Parasympathetic system affects pacemaker potential/heartbeat

affects K+ channels and Na+ F-type channels to increase permeability of K+ and decrease permeability of Na+ → slower depolarization, quicker repolarization → hyperpolarization (further from threshold) → decreases heart rate

SA node is controlled by the

• Autonomic Nervous System

• Cardiac control center

SA node controlled by autonomic nervous system (response to environment)

• sympathetic

  • norepinephrine and epinephrine bind to B1 adrenoceptors on SA node, AV node, and myocardial cells (atria and ventricles) → increases heart rate and myocardial contraction

    • epinephrine released by adrenal medulla

    • norepinephrine released by postganglionic fibers

• parasympathetic

  • Acetylcholine binds to muscarinic receptors on SA node, AV node, and myocardial cells (atria and ventricles) → slows heart rate

    • acetylcholine released by vagus nerve

SA node controlled by cardiac control center (response to cardio system)

• in medulla (decrease and increase heart rate)

• baroreceptors in aorta and carotid arteries (directly through SA node) = mechanoreceptors that respond to how much stretch there is

  • more stretch (more blood flow) → more AP sent → APs inhibit sympathetic and activate parasympathetic → decrease heart rate

Cardiomyocyte action potential differences from Skeletal

Have Ca2+ L-type channels and transient K+ channels

Steps of Cardiomyocyte Action Potential

1. Na+ enters through voltage gated Na+ channels → depolarization

2. Transient K+ channels open and some K+ exits → partial repolarization

3. Plateau because Ca2+ L-type channels open and Ca2+ enters (preventing rapid repolarization)

4. K+ permeability increases and Ca2+ permeability decreases so more K+ exits → full repolarization

Steps of cardiomyocyte contraction (calcium induced calcium release)

1. Voltage gated Na+ channels open → depolarization

2. Ca2+ L-type channels open → influx of Ca2+

3. Ca2+ causes DHP to pull open ryanodine

4. Ca2+ released from SR

5. Ca2+ binds to troponin

6. Cross bridge cycling

Cardiac muscle and tetanic contraction

Cardiac muscle does not have tetanus

• has long absolute refractory periods → slow repolarization prevents another depolarization → less fatigue

• need periods of relaxation or else blood wouldn’t go back into the heart (fill)

117/76 mmHg

• Top = systolic = ventricle pushing blood out

• Bottom = diastolic = ventricle relaxing

Normal bp

below 120/80 mmHg

Systole

• Ventricle contraction and atria relaxation

• Pressure in ventricles PV > Pressure in atria (PA)

• AV valve always closed

Steps of systole

1. Isovolumetric ventricular contraction

   • Starting to squeeze ventricle but semilunar valve not open yet

   • AV valve closed because atria is relaxed

   • PV < PS

2. Ventricular ejection

   • PV > PS

   • Blood flows out of the ventricle and semilunar valves are open

Diastole

• ventricles relax and atria contract late —> ventricle filling

• PS > PV

• Semilunar valves always closed

Steps of Diastole

1. Isovolumetric ventricular relaxation

   • Both valves closed

   • Ventricle not yet filling

   • PV > PA

2. Ventricular filling

   • AV valve opens as PV decreases but still PV > PA

     • most of ventricular filling

   • Atrial contraction (PA > PV)

     • atria contract and pushes out remaining blood from atria into the ventricle

Lub Dub

sounds of valves closing

• Lub = AV valve closed

• Dub = semilunar valve closed

EDV (end diastolic volume)

Volume at the end of ventricle filling

ESV (end systolic volume)

how much blood is left in ventricle after ventricular ejection

Dicrotic notch

little jump in aortic/system pressure when semilunar valve closes

Atrial fibrillation

dysfunction in atria alone; ventricles can still function because you can still fill ventricle without atrial contraction

Exercise shortens diastole

• heart rate increases

• heart becomes more efficient at filling ventricle

  • ventricles can fill themselves easier

Cardiac output

amount of blood leaving your heart over period of time

CO = (stroke volume) / (heart rate)

What affects heart rate?

• SA node = pacemaker potential

• Sympathetic b

• Parasympathetic

• Cardiac control center

Heart rate with SA node alone - sympathetic - parasympathetic

• SA node = 100 bpm

• Sympathetic = increased

• Parasympathetic = 80 bpm

Stroke volume

amount of blood ejected per contraction

What affects stroke volume

• EDV

  • Frank Starling Law of Heart (FSLH) = increased EDV = increased preload = need more forceful contraction

  • vicinity of thick and thin filaments (farther away if stretched)

  • troponin more sensitive to Ca2+ = more cross bridge cycling

  • Ca2+ released from SR increases

• Sympathetic intervention

  • epi and nore bind to B adrenergic receptors → increase cAMP → increase ventricular contractility → stronger contraction for a given EDV

• Total peripheral (system) resistance

  • increased resistance → decreased ejection of blood → decreased stroke volume

  • LaPlace’s Law: increased resistance and wall stress → increased afterload → forces heart to work harder → decreased stroke volume

preload

tension on heart wall before ventricular contraction

afterload

tension developed in ventricle during ejection

contractility

strength of contraction at a given EDV

ex. both have same EDV but one has higher contractility, their contraction is stronger

Arteries

thick rubber bands

• low compliance

• high elasticity

Veins

thin rubber bands

• high compliance

• low elasticity

Compliance

how easily a structure stretches (high compliance = responds to pressure well)

• loss of compliance

  • aging = hardening of arteries; elastin replaced by collagen

  • arteriosclerosis = hardening of arteries; elastin replaced by collagen specifically due to high cholesterol

  • increase systolic pressure and decrease in diastolic pressure → increase in pulse pressure

What causes a pulse

artery and arteriole compliance - 1/3 of stroke volume leaves arteries during systole

Pulse pressure

difference between systolic and diastolic pressure

• pulse felt at wrists when rapid increase in pressure during systole pushes out artery wall

• Determinants

  • stroke volume —- increase in stroke volume = increase in pulse pressure

  • Speed of ejection (heart rate) — increase speed = increase pulse pressure

  • Arterial compliance — less stretch/compliance = increase pulse pressure

MAP (mean arterial pressure)

average pressure during the cardiac cycle for an individual

• MAP = DP + 1/3 (SP-DP)

• Not just halfway between SP and DP because diastole lasts almost 2 times as long

• with aging: systolic pressure increases and diastolic pressure decreases so average stays the same

• effected by:

  • cardiac output

  • total peripheral resistance

Coronary arteries only use

diastolic pressure (only receive blood flow during diastole)

Effect of compliance on pulse pressure vs MAP

Decreased compliance → increases pulse pressure

• higher systolic pressure and lower diastolic pressure

• when arteries are stiff, the vessel cannot expand to accommodate the stroke volume

decreased compliance → no change in MAP

Effect of compliance on aging

Age decreases compliance (less stretch)

• increased systolic pressure - arteries can’t stretch when blood flows from contraction

• decreased diastolic pressure - blood and pressure waves bounce back from arteries during systole instead = less diastolic pressure; less elastic recoil

Effect of compliance on arteriosclerosis (similar to aging)

Less compliance from hardening of arteries = more blood bounce back = harder blood flow because less stretch

Ischemia

lower blood flow to the heart; heart not getting enough nutrients

Ventricular fibrillations and conduction

• more impact than atria fibrillations

• angina = chest pain

• Myocardial infarction = heart attack

Veins

• Carry majority of blood

• same 3 layers as arteries but less muscle and elastic

Venous pressure determines stroke volume

pressure in veins determines how much blood gets back to heart and pumped out to arteries

• pressure in veins < arteries

Maintaining venous pressure

• smooth muscle control

• valves = prevent blood flow back

  • varicose = broken valves = blood just sits

• muscle movement aids blood flow

  • edema = blood gets stuck → swelling because lack of muscle movement

  • Skeletal muscle pump = when you move (skeletal muscle contracting), it causes veins to compress → more blood flow to heart

  • Respiratory muscle pump = when you breathe, blood moves back → increase venous return

3 types of capillaries

• Continuous = no pores → reduced access of blood to tissue (BBB)

• Fenestrated = pores = water filled channels

• Discontinuous (sinusoidal) = important for protein transfer (bathe the tissue)

Bulk flow due to hydrostatic pressures and osmotic gradients

Pressure and blood flow: arteriole → capillary → venule

1. High blood pressure (hydrostatic) moving from arteriole into fenestrated capillary

2. hydrostatic pressure (high blood pressure) causes plasma to be squeezed out of pores

3. nutrients and hormones (like O2) can leave to tissue but colloid proteins can’t leave through pores

4. capillary is concentrated with protein

5. osmosis occurs in capillaries (water moves in) because of osmotic gradient

   • hydrostatic pressure < osmotic pressure

6. pressure (blood) flow continues to venule

**Starling’s forces = hydrostatic pressure and osmotic pressure

capillary filtration

Bulk flow due to hydrostatic pressures and osmotic gradients

Capillary filtration is regulated locally via

in arterioles and capillaries

• vasoconstriction

  • lowers hydrostatic P → decreased filtration → less pushed out to tissues

• vasodilation

  • raises hydrostatic P → increased filtration → more nutrients pushed out to tissue

Local controls of arteriolar dilation

Build up of tissue metabolites and lack of O2 causes arteriole dilation

• Active hyperemia = increase in tissue metabolism → vasodilation

• Flow Autoregulation and Myogenic mechanisms (Bayliss effect) = regulations based on changes in blood pressure = vasodilate then vasoconstrict (for balance because can’t send all resources to one tissue)

Causes of Edema

fluid build up in tissues

• High hydrostatic pressure

  • high blood pressure → high hydrostatic pressure

  • vein obstruction → high hydrostatic pressure

  • vasodilation → high hydrostatic pressure

• Changes in osmotic pressure

  • plasma proteins leaking into tissue

  • tissue making too many glycoproteins

  • decrease in plasma proteins in capillaries (kidney and liver tissue not making enough)

• Lymph obstruction

Hypertension

increased arterial pressure

• increased peripheral resistance → decreased stroke volume → increased end systolic volume → increased end diastolic volume → increased contraction

Congestive heart failure can be caused by

• diastolic dysfunction

  • reduced ventricular compliance, normal contractility

    • related to ventricular hypertrophy: because cells need to work harder, cells will build up → thicker ventricle is stiffer → decreased compliance → lower EDV → lower stroke volume

• systolic dysfunction

  • reduced contractility — reduce how much response to sympathetic innervation

    • results from myocardial damage → reduced stroke volume at any given EDV

• both

Dilated Cardiomyopathy

dilated ventricle → increased afterload → harder to eject blood

Hypertrophic Cardiomyopathy

Thicker walls → harder to fill → decreased cardiac output → decreased afterload

**more common in women

echocardiogram

best way to determine likelihood of systolic vs diastolic dysfunction

ejection fraction

systolic dysfunction < 55%-70% < diastolic dysfunction

Responses to heart failure/dysfunction

Baroreceptor reflex - firing decreases

• increase sympathetic activation

• decrease parasympathetic activation

• increased peripheral resistance by artery walls by sympathetic

• increased fluid retention by kidney

Plasma volume increases → increase venous pressure → venous return volume to heart increases → EDV increases → contraction increases →

• overtime can cause

  • edema

  • or with systolic dysfunction, less contractility

Pulmonary edema

fluid in the interstitial space of lungs impairs gas exchange

Treating diastolic dysfunction

• ACE inhibitors → dilation of blood vessels → less tension

• diuretic → increase urine volume → decrease blood volume

• Ca2+ channel blockers (BAD FOR PEOPLE WITH SYSTOLIC DYSFUNCTION)

  • B1 blockers → slows down heart rate giving it more time to fill up

Treating systolic dysfunction

ACE inhibitors and diuretic → reduce peripheral resistance → reduce afterload

positive effects of exercise

• decrease resting heart rate → decreased myocardial O2 demand

• increased diameter of coronary arteries

• decreased chance of hypertension (NO)

  • nitrodilators from exercise → more dilation

• increased sensitivity to insulin and better control of blood glucose → decrease chance of diabetes

• decreased cholesterol and LDLs and increase HDLs

  • LDLs = bad cholesterol that builds up on vessel walls → atherosclerosis

  • HDLs = good cholesterol that carries LDL away from arteries back to liver

• decreased tendency for clotting and increased dissolution of clots

Steps of Respiration

1. ventilation

2. gas exchange from alveoli to blood

3. gas transport

4. gas exchange from blood to cells

5. cellular respiration

Order of respiratory branches

trachea → bronchi → bronchioles → terminal bronchioles (end of conducting zone) → respiratory bronchioles (start of respiratory zone) → alveolar ducts → alveoli