Human Physiology Midterm #3

Lecture 20

20

heart sounds

from turbulent blood flow from valves closing

first sound: softer, '“lubb”, AV valves closing simultaneously (diastole)

second sound: louder, “dubb”, semilunar valves closing simultaneously (systole)

blood flow

silent unless there is an obstruction where it becomes turbulent → most heart murmurs are valve issues

• stenotic valve: stiff, narrowed valve that doesn’t open completely

• incompetent valve: doesn’t close completely, backflow of blood & collides with forward flowing blood, or can happen from holes in the interventricular septum

blood vessel composition

as arteries divide into smaller arteries → walls become more muscular and less elastic

elastic systemic arteries are a pressure reservoir that maintain blood flow during ventricular relaxation

• systemic veins→ expandable volume reservoir

arteriole walls have layers of smooth muscle → contracts/relaxes under chemical signaling

aortic blood pressure

blood pressure in the aorta

doesn’t stay elevated during diastole because blood stops flowing into aorta → lowers blood pressure

elevated pressure in arteries during diastole is because of elastic recoil property of arteries

systolic vs diastolic pressure

systolic pressure: max pressure during systole

diastolic pressure: minimum pressure during diastole

average arterial pressure during cardiac cycle: MAP

capillaries

have small and thin walls

veins vs arteries

veins: thinner muscle, fibrous, and endothelium tissue

arteries: has elastic tissue

pulse pressure

pressure increase generated by left ventricle ejecting blood creates pressure/pulse wave in arteries

measure of strength of pressure wave

• pulse pressure= systolic pressure - diastolic pressure

venous blood flow is steady (not pulsatile)

Mean Arterial Pressure (MAP)

represents driving pressure created by pumping of heart

MAP= diastolic pressure + 1/3 pulse pressure

• hypotension: blood pressure is too low (fainting)

• hypertension: blood pressure is elevated (rupture vessels)

measuring blood pressure

arterial BP measured with a sphygmomanometer & stethoscope

1. sphygmomanometer has inflatable cuff, when inflates above systolic pressure arterial blood flow is stopped → no sound heard above brachial artery

2. when cuff pressure is btw systolic & diastolic pressure → turbulent blood flow (Korotkoff sounds) can be heard thru compressed artery

3. when cuff pressure is below diastolic pressure → artery is no longer compressed and blood flow is silent

cardiac output (CO)

amount of blood pumped out of each ventricle in one minute

product of heart rate (HR) & stroke volume (SV)

CO= HR * SV

heart rate & parasym vs sym activity

HR is initiated by autorhythmic cells in SA node @ 100 bpm

@ resting state → more parasympathetic than sympathetic activity to heart → normal resting HR is lower (70 BPM)

sympathetic NS activity increases HR

sympathetic NS activity raises HR: epinephrine/nerves ↑ → B-adrenergic receptors in SA node activated by epi → increase open state of F-type Na & T-type Ca2+ channels → increases rate of spont depol → increase HR

parasympathetic NS activity decreases HR

increased parasympathetic activity (vagus nerve) → muscarinic cholinergic receptor in SA node → increased open state of K+ channels and closed state of Ca channels → decrease rate of spon depol & hyperpol cell → decreased HR

sympathetic NS

can increase the force of contraction at any given end-diastolic ventricular volume → which increases stroke volume

Frank-Starling principle

the heart will pump all the blood that returns to it → strength of contraction increases as the end-diastolic ventricular volume increases

increasing end-diastolic volume stretches muscle → brings fibers closer to optimum length → optimum length = greater strength of contraction → increased stroke volume and cardiac output

SV is increased by increase in end-diastolic volume & increase in contractility to due sym stimulation/epinephrine

factors determining cardiac output

MAP

regulated by homeostatic mechanisms, influences blood flow to all organs in systemic circuit

MAP = CO * TPR (total peripheral resistance)

• Total peripheral Resistance (TPR): sum of resistances to flow by all systemic blood vessels

baroreceptor reflex

primary short-term reflex pathway for homeostatic control of MAP, increases MAP

sensory receptors of the baroreceptor reflex are in walls of carotid arteries and aorta → carotid baroreceptors in brain, aortic baroreceptors in body

baroreceptor reflex arc components

stimulus: change in BP

integrating center: medullary cardiovascular control center (CVCC) in medulla oblongata

• initiates a rapid response→ changes in CO & TPR within 2 heartbeats of stimulus

• output signals from CVCC are carried by sym & parasym neurons

peripheral resistance

under tonic sympathetic control → increased sym discharge causes vasoconstriction

baroreceptor firing frequency

changes w BP

high BP → stretches baroreceptor membranes → firing rate increases

low BP → firing rate of baroreceptors decreases

heart is regulated by

antagonistic control

• increased sym activity → increases HR, shortens conduction time thru AV node, enhances force of myocardial contractions

• increased parasym activity→ slows HR, small effect on ventricular contraction

arterial baroreceptor reflex

functions as a SHORT-term regulator of arterial BP, if BP changes for long time the baroreceptors simply adapt

BP control includes rapid responses from cardiovascular system & slower responses from kidneys

if blood volume increases, BP increases

hard to compensate for decreased blood volume → kidneys can only conserve BV (blood volume) not restore it

increase in excretion of urine restores BV to normal

increased BV due to increased fluids → increase in arterial pressure

Lecture 21

21

respiratory function

pulmonary ventilation: movement of air into lungs (inspiration) & out (expiration) via bulk flow

exchange btw lung air spaces & blood via diffusion

transport O2 & CO2 btw tissues via blood

exchange O2 & CO2 btw blood & body tissues via diffusion

Fick’s Law

states that rate of diffusion of a gas depends on 5 parameters

• solubility of gas in aqueous film lining gas exchange surface

• temperature

• surface area available for diffusion, A

• difference in partial pressure of gas across surface, P2-P1

• thickness of barrier to diffusion, D

respiratory epithelia are thin (D is small) and folded (A is large), large pressure gradient (P2-P1 is large)

K is diffusion constant, A is area for gas exchange

upper airways

air passages of head & neck → nasal cavities, oral cavities, pharynx

air enters thru the cavities which lead to pharynx → food enters esophagus & air enters larynx

respiratory tract

2 components→ upper conducting zone & lower respiratory zone

upper conducting zone:

• conducts air from larynx to lungs

• begins w the larynx (tube containing vocal cords)

lower respiratory zone:

• contains sites of gas exchange within lungs

• thinner walls

larnyx

opens into 2 main bronchi→ one of which enters each lung (right & left bronchi)

each bronchi divides into secondary bronchi→ right side into 3, left side into 2 → continues to branch out (millions)

alveoli

major sites of gas exchange btw each other and blood

attached to walls of respiratory bronchioles, increases in amount near alveolar ducts

terminate in clusters called alveolar sacs

alveolar sac

surrounded by elastic fibers & network of capillaries

type I alveolar cells

thickly covers the air-facing surface of 1 alveolar wall, all flat

permits gas-exchange

type II alveolar cells

secretes surfactant that reduces surface tension in alveoli → allows better expansion

pleural sac

fluid that surrounds each lung

double membrane→ parietal pleural side lines chest wall, visceral pleural membrane lines the lung

like a fluid filled balloon surrounding an air-filled balloon

ventilation

air moves down a pressure gradient from pressure of atmosphere to alveoli

• inspiration happens when alveoli pressure is less than atmosphere pressure

• expiration happens when atmosphere pressure is less than alveoli pressure

4 pressures in lungs

atmospheric pressure

intra-alveolar pressure

intra-plural pressure

transpulmonary pressure

atmospheric pressure

Patm

pressure of outside air

constant, 0 mmHg

intra-alveolar pressure

Palv

pressure of air in alveoli

varies w phase of respiration → during inspiration it is negative (less than Patm) & during expiration it is positive

ventilation is driven by Palv-Patm

intra-plural pressure

Pip

pressure inside the pleural sac

always negative because of elasticity in lungs & chest wall → opp forces pull on intra-pleural space (chest wall outward, lungs inward)

surface tension of intrapleural fluid hold wall & lungs tg

always less than Palv

-4mmHg

transpulmonary pressure

Palv - Pip

distending pressure across lung wall

increase in transpulmonary pressure creates a larger distending pressure

wound to pleural sac

pleural sac must be airtight → if punctured then negative Pip is lost → lungs recoil and collapse while chest wall expands → pneumothorax

air flow mechanism & Boyle’s Law

air flow is driven by pressure gradients that respiratory muscles create by changing the volume of the lungs

• Boyle’s Law: pressure in inversely related to volume → can change alveolar pressure by changing volume

inspiration to expiration & pressure

start of inspiration: lungs expand from contraction of inspiratory muscles → lowers Palv so air is drawn into lungs

next: Palv falls at first but then rises because of increase of air molecules flowing in, when Palv=Patm air flow inward stops

finally: lung volume decreases, Palv increases → air flows out, amount of airflow in alveoli decreases which lowers pressure to 0

inspiration initiation (active expiration)

by neural stimulation of inspiratory muscles → ACh is released → causes contraction of the diaphragm → diaphragm flattens and moves down → contraction of external intercostals make ribs go up and out to expand chest wall

• as chest expands it pulls out on intrapleural fluid → makes Pip decrease → causes increase in transpulmonary pressure → causes larger distending pressure across lungs → inflation of lungs Palv < Patm

quiet breathing expiration

passive process, no muscle contraction

when motor neurons stop firing → inspiratory muscles relax → lungs/chest wall recoil to OG positions → volume of thoracic cavity decreases Palv > Patm → air flows out until Palv = Patm

2 factors affecting pulmonary ventilation

lung compliance: measure of ease which they can be stretch, lungs are elastic and recoil after being stretched

• elasticity & surface tension

airway resistance: resistance of the entire system of airways in the respiratory tract

lung compliance

change in lung volume that results from transpulmonary pressure change

big lungs = better → smaller change in transpulmonary pressure needed to bring in air, less muscle contraction

elasticity

elastic fibers oppose lung expansion → lungs stretch, fibers recoil

emphysema results in destruction of elastin fibers in lung tissue → lungs have high compliance and stretch easily but don’t recoil back to resting position for expiration

surface tension

the greater the ST the more work needed to spread the fluid out

created in lungs by thin layer of fluid lining the internal surface of the alveoli → as lungs expand work is required to stretch elastic tissue but to increase SA of fluid layer

big ST = less compliant

Laplace’s Law

P = 2T/r

pressure = 2*surface tension / radius

air pressure is directly proportional to surface tension & inversely proportional to alveolar radius

pulmonary surfactant

decrease ST in alveoli, secreted by type II alveolar cells

increases lung compliance

stabilizes alveoli of diff sizes (r) by differentially altering surface tension to allow them to have same pressure

Newborn Respiratory Distress Syndrome (NRDS)

risk for premature babies, develops by 34th week

lungs have low-compliance (stiff) low surfactant → alveoli collapse completely and must completely re-inflate → waste energy → use steroids that increase surfactant production to treat

airway resistance

when resistance increases → large pressure gradient required to make air flow

determines how much air flows into lungs at any given pressure (major determinant)

Lecture 22

22

gas exchange

involves diffusion of O2 & CO2 from regions of higher to lower partial pressure

gases are expressed as partial pressures because gas is mixture of more than 1 molecule

Dalton’s Law

Ptotal= P1 + P2 + P3 + P4 + Pn

total pressure of such a gas is the sum of the pressure of individual gases that make up the mixture

partial pressure: proportion of the pressure of the entire gas that is due to the presence of the individual gas

atmosphere is 79% N2 & 21% O2

solubilities of gasses in liquids

when a gas is in contact w water → pressure gradient, gas molecules move from gas to water IF gas pressure is higher than water pressure → continues until equilibrium

oxygen has low solubility in aqueous solution, CO2 is more soluble

carbonation

water in contact w normal air has negligible carbonation

when cool water and combine w high pressure CO2 → gas moves into water → carbonation

normal alveolar Po2

100 mmHg while deoxygenated venous blood is 40mmHg

Pco2

of arterial blood is 40mmHg

• it’s lower than Pco2 of cells (46mmHg) → CO2 diffuses out of cells into capillaries

Po2 of aterial blood

leaving lungs is 100mmHg

when arterial blood reaches capillaries → gradient is reversed → intracellular Po2 partial pressure is lower than 40mmHg → O2 travels down pressure gradient

oxygen solubility

per 1 liter of arterial blood has 200ml of O2

only 3ml dissolves in 1 Liter of blood & 197 ml of O2 is transported in RBCs combined w hemoglobin

hemoglobin (Hb)

protein made of 4 subunits → each subunit consists of heme & polypeptide attached

each heme group has 1 Fe+ ion which O2 binds to

O2 + Hb (deoxyhemoglobin) →← HbO2 (oxyhemoglobin)

percent Hb saturation = (O2 bound to Hb/max capacity of Hb to bind O2) × 100

O2-Hb dissociation curve

relationship btw Po2 & % hemoglobin saturation → shape reflects properties of Hb molecule and affinity for O2

at normal Po2 (100mmHg) 98% of Hb is bound to O2

as blood passes thru lungs under normal conditions Hb picks up almost max O2

at Po2 above 100mmHg → only minor changes in % of Hb saturation

• alveolar Po2 can be <100mmHg w/o lowering % Hb sat significantly

more about O2-Hb dissociation curve

once Po2 falls from 100 to 60 the % Hb sat becomes steeper → small decrease in Po2 causes large release of O2

in blood leaving systemic capillaries w a Po2 of 40 → Hb is still 75% sat → cells release only 25% of its O2 → remaining O2 stays bound to serve as a reservoir

O2 affinity to hemoglobin

each subunit combines w 1 O2 molecule → rxns of 4 subunits are sequential, each combo facilitates the next

DeoxyHb subunits are tightly held by electrostatic bonds in conformation w low affinity for O2

binding of O2 breaks bonds → conformational change → remaining O2 binding sites more exposed → binding of 1 O2 increases affinity of other sites

O2 affinity hemoglobin chart

• if shifts left → more loading of O2, less unloading

• if shifts right → less loading of O2, more unloading

factors that affect Hb sat

temp, acidity, blood DPG (makes Hb have less affinity, releases more O2 to cells)

• increase in these causes a shift to the right (decrease affinity)

• decreases causes a shift to the left (increase affinity)

molecules w greater affinity facilitate O2 delivery

fetal Hb→ high affinity for O2 than adult Hb → fetus can steal O2 from mom’s blood

myoglobin→ high affinity for O2

Hb has a higher affinity for CO than O2 → makes it v toxic

CO2 is transported in blood in 3 ways

First way is:

only 7% of CO2 carried by venous blood is dissolved in blood, other 93% diffuses into RBCs → 70% is converted to bicarbonate & 23% binds to hemoglobin

2nd way CO2 is transported in blood

conversion of CO2 to bicarbonate (HCO3-) depends on carbonic anhydrase (CA) enzyme in RBC

products (bicarbonate) must be removed from cytoplasm of RBC → 2 mechanisms remove H+ and bicarbonate

• antiport protein exchanges HCO3- for Cl- → chloride shift

• deoxyhemoglobin in RBC bind H+ → has a greater affinity for H+ than oxyHb

3rd way CO2 is transported in blood

about 23% of CO2 in venous blood binds directly to Hb → when O2 leaves binding sites on Hb, Co2 binds w free Hb at amino groups → forms carbaminohemoglobin

CO2 transport summary

• CO2 diffuses out of cells into systemic capillaries

• 7% of Co2 is dissolved in plasma

• 23% of CO2 binds to Hb to form carbaminoHb

• 70% of Co2 is converted into bicarbonate & H+, Hb buffers H+

• HCO3- enters plasma in exchange for Cl- (chloride shift) → transported to lungs → @ lungs dissolved CO2 diffuses out of plasma → CO2 unbinds from Hb and diffuses out of RBC → carbonic acid rxn reverses, pulls HCO3- back into RBC and converts to CO2

Lecture 23

23

spirometer

device that measures volumes of inspired and expired air

breathe into tube that converts air into electrical signal

3 of 4 non-overlapping lung volumes make total lung capacity, including tidal volume, inspiratory volume, and expiratory reserve volume

4 non-overlapping lung volumes

inspiratory reserve volume

tidal volume

residual volume

expiratory reserve volume

inspiratory reserve volume (IRV)

max volume of air that can be inspired from end of normal inspiration

tidal volume (Vt)

volume of air that moves in & out of lungs during a single unforced breath

residual volume (RV)

volume of air remaining in lungs after max expiration

expiratory reserve volume (ERV)

max volume of air that can be expired from end of normal expiration

lung capacities are sums

vital capacity is sum of?

tidal volume, inspiratory reserve volume, and expiratory reserve volume

minute ventilation

minute ventilation = tidal volume * respiratory rate

total amount of air inhaled or exhaled in a minute

minute ventilation > alveolar ventilation → because of dead space

air that remains in upper airways does not get to alveoli→ dead space

alveolar ventilation = (tidal volume -anatomical dead space) * respiratory rate

end of inspiration & dead space

end of inspiration → first exhale air comes out of dead space → at end of expiration, dead space filled w stale air from alveoli → inhale fresh air

diaphragm and intercostal muscles

both skeletal muscles, do not contract w/o stim by motor neurons

breathing depends on cyclical respiratory muscle excitation by motor nerves → inhibit nerves = no breathing

inspiratory spinal motor neurons

when AP stops → inspiratory muscles relax → expiration occurs

inspiration initiated by burst of AP in spinal motor nerves to diaphragm

medulla oblongata

holds the Pre-Botzinger complex in the reticular formation

• integration center that controls breathing

Pre-Botzinger complex: consists of pacemaker cells which create the rhythm of breathing, on either side of medulla oblongata

• PreBotC fires APs to the Phrenic Motor Neurons (lead to diaphragm, tells to contract)

• if separate PreBotC & Phrenic Motor Neurons→ breathing stops

Medulla also has:

• dorsal respiratory groups: inspiration

• ventral respiratory groups: forced/heavy breathing

medulla oblongata regulates contraction of insp & exp muscles

thru reciprocal inhibition→ motor neurons of exp muscles are inhibited when insp muscles are active & vise versa

Pontine Respiratory Group (PRG) & medulla oblongata

both regulated by cortex

• PRG fine tunes transition btw insp & exp

peripheral arterial & central chemoreceptors regulate medullary insp neurons

peripheral chemoreceptors:

• near baroreceptors controlling BP

• sense changes in Po2 levels, increased H+, & pH of plasma

• 2 types:

  • carotid bodies: strategically located to monitor O2 supply to brain

  • aortic bodies: monitor rest of body O2 supply

central chemoreceptors:

• in medulla

• stimulated by increase in H+ conc in brain ECF (from carbonic acid rxn) or in blood Pco2

• give excitatory synaptic input to medullary insp neurons

glomus cells

trigger reflex in ventilation

in carotid & aortic bodies, activated by decrease in Po2, increase in Pco2, or pH change

ventilation stimulated when arterial Po2 is less than 60mmHg OR when plasma pH lowers OR Pco2 increases

glomus cells pathway

stimulus(change in Po2/Pco2/pH) inactivates K+ channels causing glomus cell depolarization → depol opens VG Ca+ channels → Ca+ entry leads to exocytosis of NT onto sensory neuron → AP in sensory neuron leads to brain stem resp network → increase ventilation

central chemoreceptors

located on ventral surface of medulla oblongata (brainstem)

respond to pH changes in CSF, not directly responsive to CO2

• increased CO2 decreases pH

central chemoreceptors set the respiratory pace

arterial Pco2 increases → CO2 crosses the BBB → CO2 in CSF is converted into carbonic acid → carbonic acid dissociates into bicarbonate & H+ → central chemoreceptors activated by H+ → receptors signal the control network to increase ventilation rate & depth → CO2 is removed from blood

ventilation stimulated by chemoreceptors by:

• a LARGE decrease in arterial Po2

• arterial Pco2 increases A LITTLE

Lecture 24

24

central chemoreceptors

located on ventral surface of the medulla

sets the respiratory pace by providing continuous input into control network

respond to pH changes in CSF, not directly responsive to CO2

• increased CO2 decreases pH

negative feedback loop for central chemoreceptors & CO2

arterial Pco2 increases → Co2 crosses BBB → Co2 in CSF is converted to carbonic acid → carbonic acid readily dissociates into bicarbonate and H+ → central chemoreceptors are activated by H+ → receptors signal the control network to increase rate and depth of ventilation → CO2 is removed from blood