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RESPIRATORY	PHYSIOLOGY	- II
DR.	ADNAN	MUSTAFA		(SENIOR	CONSULTANT)
DR.	SUMAYYA	ABOOBACKER		(PGY-1	RESIDENT)
Anesthesiology	Department
Topics	reviewed	in	the	previous	session
• Functional	Respiratory	Anatomy
• Mechanism	of	Breathing
• Lung	Mechanics	and	Volumes
• Work	of	Breathing
Topics	in	today’s	session
• Compliance	&	Flow	Volume	Loops
• Ventilation	Perfusion	Relationship
• Transport	of	𝑶 𝟐 and	𝑪𝑶 𝟐	in	Blood
• Regulation	of	Respiration
COMPLIANCE	&	FLOW	VOLUME	LOOPS
Compliance
• A	useful	measure	of	elastic	recoil	of	lung/chest	wall	or	both.
• It	is	defined	as	a	change	in	volume	divided	by	the	change	in	pressure.		
• Δ𝑉/Δ𝑃
Pressure-Volume	Curve
Flow-Volume	Loop
Flow-Volume	Loop	Variants
VENTILATION	AND	PERFUSION
Ventilation	Distribution
• Ventilation	distribution	 within	the	lung	depends	on	the	compliance	of	alveoli	and	the	relative	
distending	pressure.
• Theoretically,	the	pressure	within	all	the	alveoli	in	the	lung	is	constant,	but	the	pressure	outside	the	
alveoli	is	heterogenous	 throughout	 the	lung,	resulting	in	different- sized	alveoli.	
• Ventilation	distribution	 is	also	affected	by	anatomy	and	flow	rates.
• Central	regions	of	the	lung	are	preferentially	ventilated,	but	as	flow	rates	are	increased,	this	
ventilatory	difference	is	minimized.
• Simply	stated,	during	spontaneous	 ventilation,	more	gas	is	distributed	 to	gravity- dependent	areas.
PERFUSION	DISTRIBUTION
Pulmonary	circulation
• The	pulmonary	 circulation	is	the	portion	of	the	circulatory	system	which	carries	deoxygenated	blood	
away	from	the	right	ventricle	of	the	heart,	to	the	lungs,	and	returns	oxygenated	blood	 to	the	left	
atrium	and	ventricle	of	the	heart.	The	term	pulmonary	 circulation	is	readily	paired	and	contrasted	
with	the	systemic	circulation.	The	vessels	of	the	pulmonary	 circulation	are	the	pulmonary	 arteries	
and	the	pulmonary	 veins.	
• A	separate	system	known	as	the	bronchial	circulation	supplies	oxygenated	blood	 to	the	tissue	of	the	
larger	airways	of	the	lung.
VENTILATION	AND	PERFUSION	RELATIONSHIP
The	V/Q	ratio	is	the	balance	between	the	ventilation	(bringing	 oxygen	in	to	/removing	 𝐂𝐎 𝟐 from	the	
alveoli)	and	the	perfusion	 (removing	 𝐎 𝟐 from	the	alveoli	and	adding	 𝐂𝐎 𝟐).	The	V/Q	ratio	is	important	
because	the	ratio	between	the	ventilation	and	the	perfusion	 is	one	of	the	major	factors	affecting	the	
alveolar	(and	therefore	arterial)	levels	of	oxygen	and	carbon	dioxide.	
Variable Normal Value
PAO2 ~ 100 mm Hg
PACO2 40 mm Hg
PaO2 95 - 100 mm Hg
PaCO2 40 mm Hg
• Decrease	the	V/Q	ratio	:	A	decrease	in	the	V/Q	ratio	is	produced	 by	either	decreasing	ventilation	or	
increasing	blood	flow	(without	 altering	the	other	variable).	These	will	both	have	the	same	effect	- the	
alveolar	(and	therefore	arterial)	levels	of	oxygen	will	decrease	and	the	𝐂𝐎 𝟐 will	increase.	
• When	you	consider	a	decrease	in	the	V/Q	ratio,	all	you	need	to	remember	is:	
• Ventilation	is	not	keeping	pace	with	perfusion.
• The	alveolar	oxygen	levels	will	decrease,	which	will	lead	to	a	decrease	in	arterial	oxygen	levels	
(Pa𝐎 𝟐)
• The	alveolar	𝐂𝐎 𝟐 levels	will	increase	(we're	not	getting	rid	of	it	as	fast),	also	leading	to	an	
increase	in	arterial	𝐂𝐎 𝟐 .	
• To	increase	the	ventilation-perfusion	ratio.	
• Increase	in	the	V/Q	ratio	means	that	ventilation	is	in	excess	of	the	metabolic	needs	being	met	by	
perfusion,	 so	we	blow	off	 𝐂𝐎 𝟐 (lower	PA𝐂𝐎 𝟐 )	and	increase	our	P𝐀𝐎 𝟐 (and	Pa𝐎 𝟐).
Changing	the	V/Q	Ratio	Physiologically
• In	the	case	of	standing	up,	more	blood	goes	to	the	base	of	the	lung,	while	relatively	less	air	gets	
there.	That	means	we	see	a	LOW V/Q	ratio	and	LOW	P𝐀𝐎 𝟐 and	Pa𝐎 𝟐.	(along	with	high	PA𝐂𝐎 𝟐).	
• At	the	apex	of	the	lung,	we	get	relatively	less	blood	(gravity	pulls	it	down,	not	up)	and	relatively	high	
ventilation,	so	we	have	a	high V/Q	ratio.	It	leads	to	an	increase	in	alveolar	and	arterial	oxygen	levels	
while	decreasing	the	carbon	dioxide.
Changing	the	V/Q	Ratio	Pathologically	
• Increasing	the	V/Q	ratio	to	infinity. Pulmonary	 embolism
• This	blood	will	be	very	well	oxygenated	(lots	of	ventilation,	little	perfusion)	 and	have	a	very	low	
𝐂𝐎 𝟐.
• Not	much	blood	 gets	through	 to	these	alveoli,	so	the	volume	of	blood	in	this	condition	is	very	
low.	However,	5	liters	of	blood	is	still	coming	to	the	lungs	every	minute	- the	blood	that	can't	get	
to	the	area	of	lung	affected	by	the	embolism	gets	shunted	to	other	parts	of	the	lung	(leading	to	
a	low	V/Q	ratio	in	those	parts	of	the	lung).	
• We	wasted	energy	by	bringing	 ventilation	to	this	area	- in	fact,	this	is	alveolar	dead	space.
Changing	the	V/Q	Ratio	Pathologically	
• Decreasing	the	V/Q	ratio	to	zero:
• In	this	case,	we	wasted	cardiac	effort	to	send	the	blood	to	the	lungs	even	though	 nothing	
happened	to	it	as	far	as	oxygen	and	carbon	dioxide	go.	We	call	this	a	physiological	shunt -
although	the	blood	travelled	to	the	lungs,	 it	didn't	get	any	oxygen.	
• In	contrast,	an	anatomical	shunt occurs	when	the	blood	physically	doesn't	enter	the	lungs	(e.g.	a	
right-to-left	shunt	- the	blood	 jumps	straight	from	the	right	ventricle	to	the	left	ventricle	without	
going	to	the	lungs).	The	end	result	is- some	of	the	arterial	blood	has	very	low	oxygen	and	high	
𝐂𝐎 𝟐.
Shunt	Equation
• Steps	taken	by	the	body	to	normalize	the	V/Q	ratio:
• Hypoxic	vasoconstriction:	In	cases	where	the	V/Q	ratio	is	low	(lots	of	blood	or	too	little	
ventilation),	hypoxic	vasoconstriction	can	occur	and	cause	the	blood	coming	into	the	area	to	be	
directed	to	other	parts	of	the	lung.	Decreasing	the	perfusion	 of	the	hypoxic	region	will	raise	the	
V/Q	ratio	and	bring	the	arterial	blood	gases	closer	to	what	we	expect.	
• Bronchoconstriction:	In	cases	of	high	V/Q	ratio,	the	bronchi	will	constrict	slightly	to	increase	the	
resistance	and	decrease	the	amount	of	ventilation	coming	into	an	area	that	is	not	well	perfused	
(although	 it	won't	shut	it	down	entirely).	This	limits	the	amount	of	alveolar	dead	space	that	
occurs	and	minimizes	the	'wasted'	work	that	occurs	with	alveolar	dead	space.
A-a	gradient
• P𝐀𝐎 𝟐 – Pa𝐎 𝟐
• A	normal	A–a	gradient	for	a	young	adult	non-smoker	 breathing	air,	is	between	5–10	mm	Hg.
• It	gives	an	idea	about	the	cause	of	hypoxemia.
• However,	the	A–a	gradient	increases	with	age.
Alveolar	Gas	Equation
• It	is		used	to	estimate	alveolar	partial	pressure	of	oxygen	or	alveolar	oxygen	tension
Oxygen	Cascade
• It	It	is	the	process	of	diminishing	 or	declining	O2	tension	from	:
Atmospheric	Air
Alveoli
Arterial	Blood	Tissue
Capillaries
Mitochondria
TRANSPORT	OF	𝐎 𝟐 AND	𝐂𝐎 𝟐	IN	BLOOD
Some	Basics.
• The	body	uses	approximately	250	mL	O2/min	at	rest.
• O2 consumption	 =	VA x	(Fi – FE)
=	5000	x	(0.21	– 0.16)
=	250	mL/min
• 21	%	O2 present	in	air	which	corresponds	to	approximately	21	kPa	(atmospheric	pressure	is	101.3	kPa).
𝐎 𝟐 and	𝐂𝐎 𝟐	Transport	in	Lungs
• 2	modes:	Convection and	Diffusion
• The	pulmonary	 diffusion	 capacity/ability	of	𝐂𝐎 𝟐 to	pass	between	the	alveoli	to	blood	is	20 times	more	
than	Oxygen	which	allows	it	to	diffuse	across	the	alveolar	membrane	with	greater	efficiency.
• Diffusion	 allows	for	𝐎 𝟐 and	𝐂𝐎 𝟐 to	be	exchanged	at	the	alveoli-pulmonary	capillary	interface	along	a	
concentration	gradient.
𝐎 𝟐Transport	in	Blood
• 𝐎 𝟐 is	carried	in	blood	 in	2	forms:
1. Dissolved	in	plasma	(2%)
2. Reversibly	bound	 to	Haemoglobin	 (98	%)
• The	Hb	molecule	consists	of	four	intertwined	subunits,	 each	of	which	consists	of	a:
• Polypeptide	globin	 chain	(alpha	or	beta)
• Haem	group	(porphyrin	 ring	containing	a	Fe2+ ion)
• 𝐎 𝟐 binds	reversibly	to	the	Fe2+ ion	in	the	haem	group,	 each	Hb	molecule	holding	 up	to	four	𝐎 𝟐
(one	to	each	Fe2+)
Oxygen	Haemoglobin	Saturation	Curve
• The	pattern	of	the	binding	produces	the	characteristic	S	shape	of	the	curve	relating	P𝐎 𝟐 to	Hb-𝐎 𝟐 saturation.
Oxygen	Haemoglobin	Saturation	Curve
• The	P50 is	the	P𝐎 𝟐 at	which	the	Hb-𝐎 𝟐 saturation	is	50%,	normally	around	3.5	kPa.	It	is	a	reference	point	that	
describes	the	position	of	the	curve	and	changes	as	the	curve	moves	under	different	conditions.
Factors	that	Influence	Oxygen	Binding
1. Temperature
2. pH :	A	decrease	in	pH	by	addition	of	carbon	dioxide	or	other	acids	causes	a	Bohr	Shift.nA Bohr	shift	is	
characterized	by	causing	more	oxygen	to	be	given	up	as	oxygen	pressure	increases.
3. 2,3-Diphosphoglycerate (DPG)	:	It	is	the	main primary	organic	phosphate. DPG	binds	to	haemoglobin	
which	rearranges	the	haemoglobin	 into	the	T-state,	thus	decreasing	the	affinity	of	oxygen	for	
haemoglobin
𝐂𝐎 𝟐	Transport	in	Blood
• 𝐂𝐎 𝟐 is	transported	in	the	blood	 in	3	different	forms	:-
• Either	dissolved	in	blood	 (5	%)	or	
• transported	as	bicarbonate	(90	%)	or	
• as	a	carbo-amino	(5%)	compound.
Haldane	Effect
• The	Haldane	Effect	describes	the	phenomenon	 by	which	binding	 of	oxygen	to	haemoglobin	 promotes	
the	release	of	carbon	dioxide.	In	many	ways,	the	Haldane	Effect	is	the	mirror	image	of	the	Bohr	Effect,	
making	clear	that	oxygen	and	carbon	dioxide	compete	for	haemoglobin	 occupancy.
REGULATION	OF	RESPIRATION
Regulation	of	Respiration
• Respiratory	Center
• Chemosensitive	Area
• Peripheral	Sensors
• Peripheral	Chemoreceptors
• Lung	Receptors
Respiratory	Center
• The	Respiratory	Center	is	located	in	the	Medulla	Oblongata	and	Pons,	in	the	Brainstem	and	are	
made	up	of	three	major	respiratory	groups	of	Neurons,	two	in	the	Medulla	and	one	in	the	Pons.	
• In	the	Medulla they	are	the	Dorsal	Respiratory	Group:	active	during	Inspiration,	and	the	Ventral	
Respiratory	Group:		active	during	both	inspiration	and	expiration	
• In	the	Pons,	the	Pontine	Respiratory	Group	includes	two	areas	known	as	the	Pneumotaxic	Centre	
(Inhibitory)	 and	the	Apneustic	Centre	(Excitatory)
Chemosensitive	Area
• This	area	located	in	the	Medulla	is	highly	sensitive	to	PaCO2 or	H+ which	in	turn	excites	the	
other	portions	 of	the	Respiratory	Center.
• The	sensory	neurons	are	specifically	excited	by	H+	ions.	However,	they	do	not	cross	the	BBB.	
But	BBB is	permeable	to	dissolved	CO2.
• Increase	in	PaCO2 à Increase	in	CSF	[H+]		à Activates	Chemoreceptors	 à Secondary
Stimulation	to	Medullary	Centers	 à Increase	Alveolar	Ventilation	 à Reduce	PaCO2 to	
normal.
• The	relationship	between	PaCO2 and	minute	ventilation	is	nearly	linear.
• Very	high	PaCO2 depress	the	ventilatory	response	(CO2 narcosis).
• PaCO2 at	which	ventilation	is	zero,	is	called	Apneic	Threshold.
Peripheral	Chemoreceptors
• Located	in	Carotid	bodies	and	Aortic	bodies.
• Carotid	bodies	(Principal	Peripheral	Chemoreceptors)	à Sensitive	to	changes	in	PaO2,	PaCO2,	pH and	
Arterial	Perfusion	pressure.
• Interact	with	the	Medulla	via	CN	IX	à reflex	increase	in	Alveolar	ventilation	in	response	to	decrease	
PaO2 and	Arterial	perfusion,	 or	elevations	of	[H+]	and	PaCO2
• Carotid	bodies	are	most	sensitive	to	PaO2
• Activity	will	not	appreciably	increase	until	PaO2 decreases	below	50	mmHg.
• Anti-dopaminegic drugs,	anaesthetics	and	bilateral	carotid	surgery	abolish	the	response	to	hypoxemia.
Respiratory	Reflexes
• Hering- Breuer	Inflation	reflex	:	Overinflated	lungs	à stretch	receptors	+	à feedback	response	à
switches	off	the	inspiratory	ramp	and	stops	further	inspiration.
• Hering-Breuer	Deflation	Reflex	:	Marked	lung	deflation	causes	a	decrease	in	Expiration	time.
• Pulmonary	irritant	receptors	:	Stimulated	by	some	types	of	irritants	that	enter	the	tracheobronchial	
tree	which	causes	coughing	and	sneezing.
• J	Receptors	:	Stimulated	especially	when	the	pulmonary	capillaries	become	engorged	 with	blood	 or	
fluids	which	can	in	turn	lead	to	dyspnea.
THANK	YOU!
Questions	?
Anesthesiology	Department

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