Transcript CVP Physiology

CVP Physiology
Lecture Notes
Jill Davis, M.A.
1
Introduction
• Review of circulation (fig 9.1)
– Systemic
– Pulmonary
– Cardiac
• Functions of the Cardiovascular system
2
Physical Properties of the Heart
• Cardiac muscle fibers
– Branched, striated
– Single central nucleus
– Intercalated discs / gap junctions
• Heart structure
– Atrial syncytium
– Ventricular syncytium
– Fibrous septum
3
Physical Properties of the Heart
• Heart structure
– Conduction fibers
•
•
•
•
•
•
SA node (sinus node, pacemaker)
Internodal fibers
AV node
AV bundle (bundle of His)
Bundle branches (left and right)
Purkinje fibers
4
Cardiac Action potentials
• Fast sodium channels and the “initial spike”
• Slow calcium channels and the “plateau”
• Potassium channels and repolarization
• Excitation-contraction coupling
5
Cardiac cycle (fig 9.5)
• Definition
• Diastole and systole
• Electrocardiogram
–P
– QRS
–T
6
Cardiac Cycle
• Importance of pressure differences
– Causing blood flow
– Pressure and valve function
•
•
•
•
Left A-V valve (mitral, bicuspid)
Right A-V valve (tricuspid)
Pulmonary semilunar valve (pulmonic valve)
Aortic semilunar valve (aortic valve)
7
Cardiac cycle
• Atrial function in the cardiac cycle
– “primer pump”
– Pressure waves
• A wave
• C wave
• V wave
8
Cardiac cycle
• Ventricle function in the cardiac cycle
– Diastole
•
•
•
•
Isovolumic relaxation
1st third – rapid filling
2nd third – slow filling
3rd third – atrial systole
– Systole
• Isovolumic contraction
• Ejection
9
Cardiac cycle
• Ventricular volumes
–
–
–
–
End- diastolic volume
End-systolic volume
Stroke volume
Cardiac output
10
Cardiac Cycle
• Aortic pressure curve
– During systole
– During diastole
• Heart sounds
– 1st
– 2nd
– 3rd
11
Regulation of Heart Pumping
• Intrinsic – Frank Starling’s Mechanism
– Length tension relationship
– Frank Starlings “Law” – CO = VR
• Extrinsic – autonomic nervous system
– Sympathetic
– parasympathetic
12
Factors affecting the heart
• Hyperkalemia (increased potassium)
– Slows HR
• Hypercalcemia (increased calcium)
– Speeds HR
• Temperature increase
– Speeds HR
13
Conduction System
• Sinus (sinoatrial, SA) node
– Location
– Function
• Internodal Pathways
• Atrioventricular (AV) node
– Location
– Function
• AV bundle (bundle of His)
• Bundle branches and Purkinje Fibers
14
Timing of the Conduction System
• See figures 10-3 and10-4
15
Electrocardiogram
• What does it measure?
– Amplitude and direction of waves of
depolarization and repolarization though the
heart tissue – the recording is BIPHASIC
– It is NOT a recording of action potentials of
single muscle fibers – these are
MONOPHASIC recordings which only
measure amplitude.
16
Electrocardiogram
• ECG graph paper calibration
– Vertical lines
• measurement of voltage
• 10 small lines (or 2 thick lines) = 1 mV
– Horizontal lines
• Measurement of time
• 25 small lines (or 5 thick lines) = 1 second
• Or between thick lines = 0.2 second
17
Leads
• Electrodes placed on the body are assigned
by the ECG machine as being positive or
negative
• A lead is made up of at least two electrodes
in which one electrode is the positive
reference electrode, and the other is the
negative reference electrode.
18
Standard Bipolar limb leads
• I
• II
• III
19
Einthoven’s triangle
• The three standard bipolar limb leads make
a “triangle” around the heart
20
Einthoven’s Law
• If the three standard limb leads (I,II,III) are
placed correctly, the amplitudes (voltage) of
the QRS complexes from these leads will
have the following relationship:
II = I + III
• This is known as Einthoven’s law
21
Augmented Leads
• These leads use two negative reference electrodes
• aVR
• aVL
• aVF
22
Precordial (Chest) Leads
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•
•
•
•
•
V1
V2
V3
V4
V5
V6
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Vectors
• Remember ECGs are biphasic
• Each lead has a vector (a directionality) to them
based on their electrode placement (e.g. lead I’s
vector is horizontally to the left)
• The electrical activity of the heart also has
direction (a vector) indicating the pathway the
depolarization or repolarization takes through the
heart.
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Vector rules
• A wave of depolarization through the heart
moving toward the positive electrode of a
lead will record a positive deflection on an
ECG.
• A wave of depolarization through the heart
moving away from the positive electrode of
a lead will record a negative deflection on
an ECG.
25
Vector Rules
• A wave of repolarization through the heart
moving towards a positive electrode of a
lead will record a negative deflection on the
ECG.
• A wave of repolarization through the heart
moving away from a positive electrode of a
lead will record a positive deflection on the
ECG.
26
Vector Rules
• A wave of repolarization OR depolarization
moving at right angles to the lead vector
will show no recording.
27
Atrial depolarization
• Recall that the “P” wave represents atrial
depolarization
• The direction of depolarization through the
atria is inferior and to the left
• Using the vector rules, estimate the
expected appearance of the “P” wave in
each of the six limb leads.
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Ventricular Depolarization
• Ventricular depolarization is more complex due to
the pattern of the conduction system there.
• The QRS complex reflects this fact.
• To simplify the activity of the ventricles, we will
use a mean vector (overall direction of
depolarization)
• Using the vector rules, estimate the expected
appearance of the QRS complex in each of the six
limb leads.
29
Vector Analysis
See also supplementary handouts
• Hexaxial reference system
– Definition – using the six limb leads, a circular
graph can be created.
– This grid can be used to determine the direction
of depolarization of heart muscle.
30
Vector analysis
• Axis determination
– Normal axis
– Left axis deviation
– Right axis deviation
31
Abnormal Voltages of the QRS
complex
• Increased voltage
• Decreased voltage
• Prolonged QRS
32
Cardiac rhythms
• Tachycardia
• Bradycardia
• Sinus arrhythmia
33
Arrhythmias
• Conduction Blocks
– SA block
– AV blocks
• 1st degree
• 2nd degree
• 3rd degree
• Stokes-Adams syndrome
34
Arrhythmias
• Premature contractions
• Fibrillation
– Current of injury
– Circus movements
– Atrial vs. ventricular
• Cardiac arrest
35
Circulation
• Blood vessel wall structure
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–
–
–
–
Tunica intima
Internal elastic lamina (IEL)
Tunica media
External elastic lamina (EEL)
Tunica adventitia
36
Circulation
• Arteries
– Transports blood under high pressure away from the
heart.
– Thick walled
– Types:
• Elastic = large, conducting
• Muscular = medium, distributing
• Arterioles
– Controls blood flow into capillaries via
vasoconstriction and vasodilation
37
Circulation
• Capillaries
– Function in fluid and gas exchange with tissues.
– Composed of endothelium and basal lamina
only, no muscle.
– Types:
• Fenestrated (pores)
• Continuous – (no pores (material passes by
pinocytosis or through endothelial cell junctions)
• Discontinuous / sinusoidal – larger diameter, have
fenestrae, and discontinuous basal lamina
38
Circulation
• Venules
– Collect blood from capillaries
– In an inflammatory response:
• Due to effects of histamine and serotonin, they
become “leaky”
• Leads to edema and fluid exchange
39
Circulation
• Veins
– Transports blood back to the heart under low
pressure
– Many contain one way valves
– Thin walls (less media and IEL)
– Veins function as a “blood reservoir”
– Smooth muscles can regulate venous diameter
40
Vascular Dynamics
• Total cross-sectional areas (see table p. 144)
• Volumes (see figure 14-1)
41
Vascular dynamics
• Blood flow (volumetric)
– Is the volume of blood that passes through a vessel.
– Through each category of blood vessel, the blood flow
is normally about 5 L / min.
• Blood velocity
– The speed by which blood passes within a vessel.
– Velocity in a vessel is inversely proportional to the
cross sectional area. (measured in cm/sec or mm/sec).
42
Vascular dynamics
• Systemic blood pressures (see fig 14-2)
–
–
–
–
Mean arterial pressure
Arterial systolic pressure
Arterial diastolic pressure
Capillary pressure
• Arteriolar end
• Venous end
– Venous pressure
• Pulmonary pressures (arterial, capillary, venous)
43
Principles of circulatory control
• Supply and demand principle of blood flow
– Active tissues increase blood flow 20-30X normal
– Local control – very important = autoregulation
– Nervous control = central regulation
• Cardiac output = venous return = sum of all tissue
flows
• Arterial pressure – controlled independently of
blood flow
– Short term control = autonomic nervous system
– Long term control = kidneys (blood volume, hormones)
44
Ohm’s Law
• Q = P / R
• Q = blood flow
• P = change in pressure
• R = resistance
• Note: CO can substitute Q when considering the
entire systemic circulation rather than an
individual.
45
Blood Pressure
• Laminar vs. Turbulent flow
• Measurement of blood pressure
(sphingomanometer)
46
Resistance
• R = 8l/r4
–
–
–
–
R = resistance
 = viscosity of blood
l = length of blood vessel
r = radius of blood vessel
• Conductance = 1/R
• Viscosity
– Main determinant is hematocrit
47
Poiseuille’s Law
• This law can be constructed by combining
Ohm’s law with the resistance equation:
• Q = Pr4 / 8l
48
Effect of Pressure on vascular
resistance and tissue blood flow
• Pressure increases force  increase in P
• Pressure causes vessel distention 
decreases peripheral resistance
• Therefore, increased pressure increases
blood flow two ways.
49
Law of La Place
• T = Pr
– T = tension on vessel wall
– P = transmural pressure
– r = radius of the vessel
•  = Pr/ (a variation on the Law of La Place)
–  = wall stress
– P = transmural pressure
–  = wall thickness
50
Distensibility and Compliance
• Examples where vascular distensibility is
important
– Increased pressure causes arterial dilation
– Averaging of pressures in arterioles
– Venous reservoir function
• Definition of vascular distensibility
– VD = increase in volume / increase in pressure X
original volume
• Therefore – dispensability is related to a vessel’s
ability to distend with increase in pressure
51
Distensibility and Compliance
• Definition of vascular compliance (capacitance)
– VC = increase in volume / increase in pressure
– Or VC = VD X original volume
• Therefore – compliance is related to the total
amount of blood that can be stored in a vessel with
increasing pressure
• Veins are 8 times more distensible, but 24 times
more compliant than arteries
52
Volume pressure curves
• A method for expressing the relation of pressure to
volume in a vessel (see fig 15-1)
• Artery – small change in volume causes a large
change in arterial pressure
• Vein – a small change in volume causes a slight
change in venous pressure
• Note the effects of sympathetic stimulation and
sympathetic inhibition to this relationship.
53
Delayed compliance (stressrelaxation) of vessels
• See figure 15-2
• Recall from biomechanics the principles of
viscoelasticity and creep
• An increase in volume will increase
pressure, then the vessel wall muscle fibers
will “creep” to a new length to decrease
pressure over a few minutes.
• A decrease in volume will have the opposite
effect
54
Pressure Pulse contours
• Definition of pulse pressure (PP)
– Systolic pressure – diastolic pressure
– PP is proportional to stroke volume and
inversely proportional to VC
– Note the effects of arteriosclerosis on VC
55
Abnormal pressure pulse
contours
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•
•
•
•
See figure 15-4
Arteriosclerosis
Aortic stenosis
Aortic regurgitation
Patent ductus arteriosus
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Transmission of pressure pulses
• See fig 15-6
• Following ejection, blood distends the aorta
• The rising pressure in the aorta then causes a wave
of blood flow through the arterial tree
• Damping – progressive loss of pulsations upon
entering the small arteries  arterioles 
capillaries
• Damping is directly proportional to resistance and
compliance
57
Veins and their Functions
• Venous pressure
– Central venous pressure
• Is the pressure in the right atrium because all
systemic veins flow into the right atrium
• Regulated by a balance between the ability of the
right side of the heart to pump blood into the lungs,
and the tendency for blood to flow into the right
atrium (venous return).
• Factors that increase venous return
– Increased blood volume
– Increased large venous tone
– Dilation of arterioles
58
Veins and their Functions
• Central venous pressure continued
– Normal right atrial pressure = 0 mm Hg
Abnormally high – up to 20-30 mm Hg
• In severe heart failure
• After excessive blood transfusion
– Abnormally low - -3 to –5 mm Hg
• In vigorously pumping heart
• In severe hemorrhage
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Veins and their Functions
• Peripheral venous pressure
– Large veins have little resistance in general
– Exception – vein compression points (see fig
15-9)
– Effect of right atrial pressure on peripheral
venous pressure
• Increase causes blood back up and an increase in
peripheral venous pressure
• Significant increases only seen in CHF
60
Veins and their Functions
• Peripheral venous pressure continued
– Effect of Intra-abdominal pressure
• When increased, it increases venous pressure in the
legs
• Intra-abdominal pressure may increase:
– Due to pregnancy
– Abdominal tumors
– Ascites (excessive fluid in the peritoneal cavity)
61
Veins and their Functions
• Peripheral venous pressure continued
– Effect of gravitational pressure (fig 15-10)
• Venous pressure above the heart is less than 0 mm
Hg
• Venous pressure below the heart is greater than 0
mm Hg
62
Veins and their Functions
• Venous valves and the “venous pump”
– Valves ensure one-way movement of blood
– Muscle pump - extremity muscle contraction
“massages” blood up toward the heart
– Thoracic pump – breathing action also “massages”
blood up toward the heart
• Venous valve incompetence causes varicose veins
in the legs (secondary to pregnancy, or excessive
time standing)
63
Veins and their Functions
• Blood reservoir function
– Recall the compliant nature of veins allows
these vessels the ability to store blood
– Principle reservoirs
•
•
•
•
•
Large abdominal veins
Spleen
Liver
Subcutaneous venous plexus
heart
64
Microcirculation
• Definition – the microscopic circulation that
occurs at the level of the tissues (capillary bed)
• Purpose – to transport nutrients to the tissues, and
remove cellular waste.
• Capillary Bed Structure (fig 16-1)
–
–
–
–
–
Arteriole
Metarterioles and precapillary sphincters
True capillaries
Preferential (thoroughfare) channels
venules
65
Microcirculation
• Vasomotion = intermittent contraction of the
metarterioles and precapillary sphincters
• Autoregulation = regulation of vasomotion
by local tissue conditions (mainly [O2]
66
Microcirculation
• Capillary walls
– Types (continuous, fenestrated,
discontinuous/sinusoidal)
– Movement through capillary walls
• Intercellular clefts (pores)
• Plasmalemmal vesicles
• Fenestrae
67
Microcirculation
• Diffusion through the capillary membrane
– Lipid soluble substances can diffuse directly
through membrane
– Water-soluble substances rely on pores and
fenestrae etc.
• Size does matter
– capillary pores are about 6-7 nm in diameter,
too small for most plasma proteins or blood
cells to pass through.
68
Interstitium
• 1/6th of the body consists of spaces between
cells = interstitium
• Components of the interstitium
–
–
–
–
Collagen fiber bundles
Proteoglycan filaments
Interstitial fluid
Together these components form a gel
69
Interstitial fluid
• Is derived by filtration and diffusion from
the capillaries
• Most of the fluid is trapped in the gel, but
some “free” fluid is found in the interstitium
• Composition – the same as plasma except it
has much less protein
70
Starling’s Forces
• There are 4 forces that determine movement
of fluid between the capillary and the
interstitium (see fig 16-5)
–
–
–
–
Capillary pressure (Pc)
Interstitial fluid pressure (Pif)
Plasma colloid osmotic pressure (p)
Interstitial colloid osmotic pressure (if)
71
Capillary Dynamics
• Each of the Starling’s forces alone cause
fluid movement across the capillary wall in
a particular direction. The actual direction
of fluid movement in a capillary is the
summative effects of all four forces.
• See tables on p. 169
• Arterial end – there is net filtration
• Venous end – there is net reabsorption
72
Lymphatic System
• Is an accessory route for the return of fluid and
protein from the interstitial space to the blood.
• Structure
–
–
–
–
–
–
Lymph capillaries
Lymph vessels
Lymph nodes
Cisterna chyli
Thoracic duct
Right lymphatic duct
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Lymph capillaries
• 1/10 of the fluid that leaves the blood
capillaries enters the lymph capillaries.
• Structure
– Blind ended
– Lined with endothelial cells that overlap to
form simple valve-like structures
– Along lymph channels, there are valves
74
Lymph flow
• Increases in the interstitial pressure will increase
lymph flow. Factors which increase Pif:
–
–
–
–
Elevated capillary pressure
Decreased plasma colloid osmotic pressure
Increased interstitial fluid colloid osmotic pressure
Increased permeability of the capillaries
• Also, these factors may lead to edema if lymph
flow rate can’t keep up with lymph formation.
75
Lymphatic Pump
• Similar to the mechanism seen in veins,
compression of the lymphatic vessels facilitate
lymph flow. (recall they also have valves)
• Sources of compression:
–
–
–
–
Contraction of surrounding skeletal muscle
Movement of body parts
Pulsations of adjacent arteries
Compression forces from outside the body
76
Functions of the Lymphatic
system
• Works as an “overflow” system for the capillaries
• Controls the concentration of protein in the
interstitial fluid
• Controls the volume of the interstitial fluid
• Controls the interstitial pressure (keeps it negative
in most tissues)
• Lymph nodes have a role in immune function
77
Local Regulation of Blood Flow
• Local blood flow changes are due to
vasoconstriction and vasodilation of arterioles,
metarterioles, and precapillary sphincters.
• Short-term (acute, metabolic) control
– Occurs in seconds to minutes
– The greater the metabolism of a tissue, the greater the
blood flow.
– Tissue oxygenation is the greatest determinant of blood
flow regulation.
78
Local Regulation of Blood Flow
• There are two theories that explain local
blood flow regulation (autoregulation)
– Vasodilator theory
– Oxygen lack theory
79
Local Regulation of Blood Flow
• Reactive hyperemia
– occurs after blood flow is interrupted to a tissue
for some time, then restored
– Autoregulation mechanisms work to increase
blood flow
– The increase in blood flow persists long after
blood flow was restored to “pay back” the
oxygen debt
80
Local Regulation of Blood Flow
• Active hyperemia
– An increase in blood flow due to the tissues
becoming very active
– Example – blood flow to exercising skeletal
muscle tissue can increase up to 20 times
normal
81
Local Regulation of Blood Flow
• Autoregulation in response to increased
blood pressure
– Increased blood flow results from an increased
blood pressure. This blood flow will return to
normal based on two theories.
• Metabolic theory
• Myogenic theory
82
Local Regulation of Blood Flow
• Increased blood flow in the arterioles and
capillaries downstream from arteries causes
release of “endothelial-derived relaxing
factor” a.k.a. nitric oxide.
83
Long-term control of blood flow
• Due to changes in vascularity
– Takes days to months to occur (age dependant)
– Oxygen still seems to be the main determining
factor in this control.
– Vascular growth (angiogenetic) factors
• Vascular endothelial growth factor
• Fibroblast growth factor
• Angiogenin
– Development of collateral circulation
84
Vasoconstrictors
• Norepinephrine and epinephrine
– From sympathetic nervous system and adrenal medulla
– Note – some vessels respond to NE and epinephrine by
vasodilation (e.g. coronary arteries)
• Angiotensin
– Is formed by a cascade initiated by renin release from
the kidneys
– It causes arteriole constriction to increase total
peripheral resistance
– increases blood pressure
85
Vasoconstrictors
• Vasopressin
–
–
–
–
A.k.a. antidiuretic hormone
Released from the posterior pituitary gland
Increases water reabsorption by the kidneys
In increased amounts, causes arteriolar
vasoconstriction
– Increases peripheral resistance and blood
pressure
86
Vasoconstrictors
• Endothelin
– Its release is triggered by endothelial damage
– Prevents excessive bleeding
87
Vasodilators
• Bradykinin
– Formed by a cascade initiated by tissue inflammation
– Causes arteriolar dilation and increased capillary
permeability
• Histamine
– Derived predominantly from mast cells and basophils
– Causes vasodilation of arterioles in inflammatory
reactions
– Also is an important mediator in allergic reactions
88
Effect of ions in vascular control
• Calcium – increases cause vasoconstriction
(stimulates smooth muscle)
• Potassium and magnesium – increases cause
vasodilation (inhibits smooth muscle)
• Hydrogen ion – increases cause dilation
(lowers pH)
89
Short-Term Regulation of Blood
Pressure
• Sympathetic nervous system
– Preganglionic
• Location
• neurotransmitter
– Postganglionic
• Location
• neurotransmitter
90
Short-Term Regulation of BP
• Sympathetic
– Innervates all vessels except capillaries, pre-capillary
sphincters, and metarterioles
– Innervates the heart (increases HR, contractility)
– Vasoconstrictor fibers – distribution
• Highly innervates kidneys, gut, spleen, and skin
• Lightly innervates skeletal muscle and brain
• Norepinephrine release binds to alpha receptors
– Vasodilator fibers – distribution
• Innervates the heart principally
• Some innervation to skeletal muscle
• Norepinephrine release binds to beta receptors
91
Short-Term Regulation of BP
• Adrenal Medulla
– Releases epinephrine and norepinephrine as
hormones
– Epinephrine – more potent stimulator of beta
receptors (vasodilation)
– Norepinephrine – more potent stimulator of
alpha receptors (vasoconstriction)
92
Short-Term Regulation of BP
• Parasympathetic
– Innervates the heart, but not the peripheral
circulation
– Acetylcholine causes decrease in heart rate and
a decrease in force of contraction
93
Short-Term Regulation of BP
• Vasomotor center – control of blood vessels
– Location – reticular substance in medulla and pons
– Vasoconstrictor area – excites the vasoconstrictor
neurons of the sympathetic nervous system
– Vasodilator area – inhibits the vasoconstrictor area
– Sensory area (tractus solitarius) – receives sensory
input from baroreceptors (blood pressure receptors )
– Regulates vasomotor tone
94
Short-Term Regulation of BP
• Vasomotor center – control of the heart
– Lateral area – controls sympathetic activity to
the heart
– Medial area – controls parasympathetic activity
to the heart via the vagus nerve
• Higher control of vasomotor center
– Motor cortex, limbic system, reticular
substance
95
Short-Term Regulation of BP
• To increase arterial pressure (short-term):
– Almost all arterioles are constricted (increase
peripheral resistance)
– Veins are constricted (increase venous return)
– The heart is stimulated (increase rate and
contractility)
– These effects occur within seconds
96
Long-term regulation of blood
pressure
• The kidneys are central in the control of
blood pressure on a long term basis by
controlling fluid and salt balance
– Pressure diuresis
– Pressure natriuresis
• Renal function curve – demonstrates the
relationship between arterial pressure and
urinary output (fluid loss) (fig 19-2)
97
Long-term regulation of BP
• Water balance is determined by…
– Renal output of water and salt
– Dietary intake of water and salt
• Infinite gain principle (fig 19-3)
– Equilibrium point – water and salt intake
matches water and salt output, and blood
pressure is normal
– When blood pressure increases or decreases,
kidney output changes to restore equilibrium.
98
Long-term regulation of BP
• Changes in the equilibrium point
– Change the level of water and salt intake
– Shift the pressure level for the renal output
curve (due alteration of kidney function or
pathology)
• When one of the above changes occur, there
will be a new equilibrium point at a new
pressure level. (fig 19-4)
99
Long-term regulation of BP
• Relationship between total peripheral resistance,
blood pressure, and kidney function: (fig 19-5)
– Recall BP = CO X R (ohm’s law)
– Will an increase in peripheral resistance cause an
increase in long term blood pressure?
– Unless there is a decrease in blood flow to the kidney,
blood pressure will return to normal within hours or
days.
– If the vasculature of the kidney is ALSO affected,
however, this will shift the renal function curve to the
right and cause hypertension.
100
Long-term regulation of BP
• Mechanism by which fluid volume
increases blood pressure (fig 19-6)
– Increased blood volume increases CO and BP
– Increased CO causes vasoconstriction (via
autoregulation), increased total peripheral
resistance, and arterial BP.
101
Long-term regulation of BP
• Salt
– Increased salt intake increases blood osmolarity
which stimulates the thirst center of the brain
(hypothalamus).
– Increased osmolarity also stimulates ADH
secretion from the posterior pituitary gland
which increases water reabsorption in the
kidneys
– Salt is cleared more slowly from the body than
water
102
Long-term regulation of BP
• Renin-Angiotensin system
– Renin – produced by the juxtaglomerular cells
of the kidneys in response to low blood
pressure.
– Renin catalyzes the the reaction:
Angiotensinogen  angiotensin I
– Angiotensin converting enzyme (lung)
catalyzes the reaction:
Angiotensin I  angiotensin II
103
Long-term regulation of BP
• Effects of angiotensin II:
– Vasoconstriction and therefore increased
peripheral resistance and blood pressure.
– Increased sodium retention by the kidneys and
therefore fluid retention
– Stimulates release of aldosterone from the
adrenal cortex; aldosterone increases sodium
retention and potassium excretion by the
kidneys.
104
Hypertension
• Mean arterial pressure (MAP) =
1/3 pulse pressure + diastolic pressure
• Example – if blood pressure is 120/80, then
MAP = (40 X .33) + 80 = 93 mm Hg
• Hypertension – MAP is greater than 110
mm Hg
105
Hypertension
•
•
•
•
•
•
Optimal blood pressure = 120/80
Normal blood pressure = <130 / <85
High normal = 130-139 / 85-89
Stage 1 hypertension 140-159 / 90-99
Stage 2 hypertension 160-179 / 100-109
Stage 3 hypertension 180+ / 110+
106
Hypertension
• There are two types of hypertension;
primary and secondary
• Primary HT = essential hypertension =
idiopathic hypertension
– No cause is known
– 95% of Americans with HT have this form
107
Hypertension
• Secondary hypertension
– Due to a known cause; usually associated with
increased extracelluar fluid volume (volume
loading)
– Examples:
•
•
•
•
Primary hyperaldosteronism
Hypersecretion of renin
Renal failure
Neurogenic causes (hyperactive SNS)
108
Hypertension
• Common treatments
– If secondary HT, treat underlying condition
– If primary HT, the following are common drugs
•
•
•
•
Diuretics
ACE inhibitors
Vasodilator drugs
Beta blockers
109
Cardiac Output
• CO = VR (also CO = SV x HR)
• Cardiac output is determined mainly by venous
return (VR)
• Factors that influence VR
– Body metabolism (local flow and autoregulation) VR is
a summation of all local blood flows
– Age
– Body size
– Gender
110
Cardiac Output
• CO will match VR via the following
mechanisms:
– Frank Starling’s mechanism (effects force of
contraction)
– Bainbridge Reflex (effects rate of contraction)
– SA node stretch (effects rate of contraction)
111
Cardiac Output
• The heart has a limit to the maximum CO it
can achieve.
– Normal (at rest) – 5 L/min
– Maximum – 13 L/min
• Cardiac output curve (fig 20-4)
– Demonstrates the effectiveness of cardiac
function at different levels of right atrial
pressure (which reflects venous return)
112
Cardiac Output
• Hyper-effective heart
– Sympathetic stimulation
– Hypertrophy
• Hypo-effective heart
–
–
–
–
–
–
–
–
Inhibition of SNS
Pathology of heart rhythm
Valve insufficiency
Hypertension
Congenital heart disease
Myocarditis
Cardiac anoxia
Toxins (I.e. diphtheria)
113
Pathologies affecting CO
• Pathologically HIGH cardiac output is due
to factors that decrease peripheral
resistance.
–
–
–
–
Beriberi
Arteriovenous fistula
Hyperthyroidism
anemia
114
Pathologies affecting CO
• Pathologically LOW cardiac output can be due to
cardiac OR peripheral factors:
–
–
–
–
–
–
–
Myocardial infarction
Valve disease
Myocarditis
Cardiac tamponade
Decreased blood volume (hemorrhage)
Acute venous dilation
Large vein obstruction
115
Venous Return Curve
• See fig 20-9
• Plateau due to low atrial pressures leading
to vein collapse.
• Mean systemic filling pressure – the venous
return becomes zero when the right atrial
pressure rises to mean systemic filling
pressure.
116
Blood Flow through Skeletal
Muscle
• Average at rest = 3-4 ml/min/100 g of
muscle tissue
• Average during exercise = 50-80 ml/min/
100 g of muscle tissue
• Effect of rhythmic muscle contraction on
blood flow
117
Regulation
• Regulation
– Local – autoregulation
– Nervous
• Sympathetic (norepinephrine) – via alpha receptors
• Adrenal (epinephrine) – via beta receptors
– Exercise effects
• Mass sympathetic discharge
– Increases HR and cardiac contractility
– Arterioles are contracted all over the body except muscles that
are working, coronary blood vessels, and cerebral blood vessels
– Capacitance vessels and reservoirs contract to increase mean
systemic filling pressure
118
Exercise
• Increase in arterial pressure – a result of
mass sympathetic discharge (previous slide)
– Compare changes in arterial pressure:
• Stress induced (little muscle activity)
• Whole body exercise
– Increased arterial pressure – increases blood
flow directly and indirectly (stress-relaxation of
arteries decreases peripheral resistance)
119
Exercise
• Increase in cardiac output – CO and VR
curves during exercise (fig 21-2)
120
Coronary Circulation
• Anatomy
– Left coronary artery and branches – supplies
the anterior and left lateral portions of the left
ventricle
– Right coronary artery and branches – supplies
most of the right ventricle and posterior part of
the left ventricle
121
Blood flow through the Heart
• Effect of cardiac muscle contraction (phasic
blood flow)
• Epicardial vs. subendocardial blood flow
• Control of coronary blood flow
– Local autoregulation
– Sympathetic nervous system
122
Blood flow through the heart
• Cardiac cell metabolism
– 70% of the heart’s energy is derived from fatty acids at
rest.
– Under anaerobic or ischemic conditions, the heart must
rely more on glucose/glycolysis. Lactic acid can cause
pain
– ATP degrades to ADP  AMP  adenosine; adenosine
diffuses out of the cardiac muscle cell and is a potent
vasodilator
– Excessive loss of adenosine can lead to cardiac muscle
death (about ½ of the heart’s adenosine can be lost in
30 minutes of ischemia.
123
Ischemic Heart Disease
Atherosclerosis
– A slow process of plaque formation
– Large quantities of cholesterol become
deposited beneath the endothelium, scar tissue
forms (fibrosis), and then calcifies (plaque)
– Partial or total blockage of coronary arteries
leads to ischemia.
124
Ischemic Heart Disease
• Acute coronary occlusion
– A sudden process
– Thrombus – a penetrating atherosclerotic
plaque can cause a blood clot to form which
quickly occludes an artery
– Embolus – a thrombus that has broken loose
from the site of origin and flows to another site
where it lodges.
125
Ischemic Heart Disease
• Collateral circulation
– Attempt by the body to restore blood supply to
ischemic tissue
– During plaque formation – angiogenesis may
occur during plaque development
– After acute occlusion – angiogenesis is too
slow to restore blood flow acutely, however,
vasodilation of collateral vessels may prevent
some cardiac muscle death.
126
Ischemic Heart Disease
• Includes the following
–
–
–
–
Coronary artery disease
Angina
Myocardial infarction
Sudden cardiac death
127
Myocardial Infarction
• Results from an acute coronary occlusion
• Muscle has little or no blood flow
• The affected area ceases to function and
may die (area of infarct)
• Most commonly affects the left ventricle
128
Myocardial Infarction
• Causes of death due to MI
– Decreased cardiac output
• Usually occurs when more than 40% of the left
ventricle is infarcted
• Systolic stretch exacerbates the decrease in CO
– Pulmonary Edema and kidney failure
• Results from the backlog of blood in the body’s
venous system
129
Myocardial Infarction
• Causes of Death (continued)…
– Fibrillation – chaotic pattern of contraction in
the ventricles may result from:
• Leakage of potassium from infarcted area
• Formation of an “injury current” (ischemic muscle
cannot repolarize effectively)
• Sympathetic reflexes
• Bulging weak muscle sets up “circus movements”
– Cardiac rupture (rarely)
130
Myocardial Infarction
• Anatomy of an infarct:
– Central area of dead cardiac myocytes
– Peripheral area of non-functional but living myocytes
• Recovery from MI
– Dead fibers are replaced by scar tissue
– Nonfunctional fibers either die ( if irreversible damage)
or recover (if reversible damage) when clot is
dissolved, or collateral circulation is adequate.
– Scar tissue retracts (shrinks) over time
– Normal tissue hypertrophies over time to compensate
for tissue lost.
131
Angina Pectoris
• Means “chest pain”
• Types
– Chronic stable angina
– Unstable Angina
– Prinzmetal’s (variant) angina
• Angina is often a prelude to MI if not
treated.
132
Treatment for Ischemic Heart
Diseases
• Life style modification
– Lose weight
– Eat a diet low in saturated fat and cholesterol
– Exercise
• Other treatments
–
–
–
–
–
Nitroglycerin
Beta blockers
TPA (tissue plasminogen activator)
Bypass surgery
angioplasty
133
Congestive Heart Failure
• Definition – failure of the heart to pump
enough blood to satisfy the needs of the
body.
• Heart failure is characterized by a reduced
cardiac output and damming up of the
venous circulation
• Heart failure is due to either systolic
dysfunction or a diastolic dysfunction.
134
Congestive Heart Failure
• Systolic Dysfunction (more common) progressive loss of contractile function of
the heart muscle
• Diastolic dysfunction – inability of heart to
expand enough to fill the ventricles properly
135
Congestive Heart Failure
• Heart failure can also be classified as Left sided,
or Right sided.
• Left heart failure causes
–
–
–
–
Ischemic heart disease
Hypertension
Valve diseases
Myocardial diseases
• These diseases cause left ventricle to hypertrophy
and/ or dilate.
136
Congestive Heart Failure
• Left sided CHF leads to:
– pulmonary congestion and edema
– Decreased renal perfusion leading to water and
salt retention
• Symptoms include dyspnea, orthopnea,
cough
137
Congestive Heart Failure
• Right Heart failure causes:
– Left sided heart failure
– Cor pulmonale
• Pure right sided heart failure leads to:
–
–
–
–
Systemic and portal vein congestion
Hepatomegaly and splenomegaly
Peripheral edema
Kidney congestion leading to water and salt retention
• In severe CHF, the patient will manifest with both
right and left heart failure symptoms
138
Congestive Heart Failure
• Dynamics of the circulation in cardiac failure (as
would occur following an MI)
• See figure 22-1
– Stage A - Reduced CO and increased right atrial
pressure
– Stage B - Sympathetic compensation – makes normal
heart muscles stronger, and increases venous tone
– Stage C – semi-chronic state; recovery of the heart
muscle, and renal fluid retention
139
Congestive Heart Failure
• If the heart is not too damaged, the excess
fluid retention actually helps cardiac output
by increasing venous return (compensated
heart failure)
• If the heart is severely damaged, the excess
fluid retention can overwhelm the heart and
lead to severe edema and death.
(decompensated heart failure)
140
Congestive Heart Failure
• Compensated Heart Failure
–
–
–
–
CO will be normal
Right atrial pressure is elevated
No further renal salt and water retention occurs
Over the ensuing weeks and months, the heart
may recover
141
Congestive Heart Failure
• Decompensated Heart failure
– Excessive fluid retention
– Overstretching of the heart (weakens it further)
– Pulmonary edema (with decreased
oxygenation)
– Renal failure
• See figure 22-2
142
Congestive Heart Failure
• Renal contribution to progressive decompensated
heart failure
– The kidney need a minimum CO of 5 L/min for normal
fluid balance
– Decreased glomerular filtration
– Activation of renin-angiotensin-aldosterone system
• Atrial natriuretic hormone – may slow the
progression of heart failure
143
Cardiac reserve
• The maximum percentage that the cardiac
output can increase above the normal level
• Examples:
–
–
–
–
–
Normal adult 300-400%
Athlete 500-600%
Moderate coronary artery disease 150-200%
Compensated heart failure – as little as 0%
Decompensated heart failure – less than 0%
144
Heart Sounds
• 1st heart sound or S1
– Closure of AV valves
– Duration of .14 seconds
– Lower pitch
• 2nd heart sound or S2
– Closure of semilunar valves
– .11 seconds
– Higher pitch
145
Heart sounds
• 3rd heart sound
– During middle third of diastole
– Caused by inrushing of blood into ventricles
– Low frequency (may be audible)
• 4th heart sound
– During atrial systole
– Caused by inrushing of blood
– Very low frequency
146
Auscultation
•
•
•
•
•
Aortic area – 2nd right intercostal space
Pulmonic area – 2nd left intercostal space
Erb’s point – 3rd left intercostal space
Tricuspid area – 5th left intercostal space
Mitral area – 5th intercostal space at midclavicular line
147
Heart Murmurs
•
•
•
•
Aortic stenosis – heard during systole
Aortic regurgitation – heard during diastole
Mitral regurgitation – heard during systole
Mitral stenosis – heard during diastole
148
Circulatory Shock
• Definition – generalized inadequacy of blood flow
throughout the body to the extent that the body
tissues are damaged.
• Cardinal features usually include a decrease in
cardiac output and decreased blood pressure
• Body tissues (including the cardiovascular system)
begin to suffer and deteriorate leading to death
within hours or days. Circulatory shock is self
perpetuating
149
Circulatory Shock
• Causes
– Cardiogenic shock
•
•
•
•
MI
Toxicity
Valve dysfunction
Arrhythmias
– Factors that decrease venous return
• Diminished blood volume
• Decreased vascular tone
• Venous obstruction
150
Circulatory Shock
• Shock may occur in patients without a
decrease in CO in some conditions:
– Excessive metabolic rate
– Abnormal tissue perfusion (blood bypasses
tissues)
151
Circulatory Shock
• Stages of shock
– Non-progressive stage (compensated stage) –
where the body’s own compensatory
mechanisms will lead to recovery without
outside help.
– Progressive stage – where shock becomes selfperpetuating until death; is reversible with
treatment
– Irreversible stage – severe shock that is
refractory to treatment
152
Circulatory Shock
• Specific types of shock include:
–
–
–
–
Hypovolemic / Hemorrhagic shock
Neurogenic shock
Anaphylactic shock
Septic shock
153
Hypovolumic / Hemorrhagic Shock
• Characterized by decreased systemic filling
pressure and therefore decreased venous return.
CO and BP then also decrease.
• Non-progressive /compensated stage
– Within 30 seconds:
• Baroreceptor reflexes (increase SNS response)
– Within 10 minutes to 1 hour:
• Reverse stress-relaxation response
• Renin-angiotensin system activation
• Vasopressin (ADH)
– Within 1-48 hours:
• Absorption of water from interstitial spaces
• Increased thirst
154
Hypovolumic / Hemorrhagic Shock
• Progressive stage (fig 24-3)
– Hallmarked by progressive deterioration of the
cardiovascular system (positive feedback loops)
– Features
•
•
•
•
•
•
•
Cardiac depression
Vasomotor failure (CNS depression)
Blockage of small vessels “sludged blood”
Increased capillary permeability (late)
Release of toxins
Cellular deterioration
Acidosis (carbonic and lactic acid)
155
Hypovolumic / Hemorrhagic Shock
• Irreversible stage
– Too much tissue damage
– Too many destructive enzymes and toxins have
been released into the tissues
– Too much acidosis
– Depletion of high-energy phosphates in the
body (creatine phosphate, ATP)
156
Hypovolumic / Hemorrhagic Shock
• Other forms of hypovolumic shock other
than hemorrhagic
– Intestinal obstruction
– Severe burns
– Dehydration (sweating, diarrhea, vomiting,
nephrotic kidney disease)
157
Neurogenic Shock
• Hallmarked by an increased vascular
capacity (loss of vasomotor tone)
• Causes
– Deep general anesthesia
– Spinal anesthesia
– Brain damage
158
Anaphylactic Shock
• Allergic response to an antigen in the
circulation
• Basophils and mast cells release histamine
which causes:
– Venous dilation
– Arteriole dilation
– Increased capillary permeability
159
Septic Shock
• Also known as “blood poisoning”
• Caused by a blood borne bacterial infection in
which the bacteria has been disseminated
throughout the body.
• Damage is due to infection itself, or due to
bacterial endotoxin release.
• Features – high fever, vasodilation, sludging of
blood, disseminated intravascular coagulation.
160
Treatment of Shock
•
•
•
•
•
•
Blood or Plasma transfusion
Dextran
Sympathomimetic drugs
“Head down” position
Oxygen therapy
glucocorticoids
161
Physiology of RBCs
• General Characteristics
–
–
–
–
–
–
–
A.k.a. erythrocytes
Lack a nucleus, ER, mitochondria
Biconcave discs
8 micrometers in diameter
Concentration in the blood ~ 5 million/cc
Contains hemoglobin (O2 transport and buffer)
Contains carbonic anhydrase
162
Physiology of RBCs
• Hematopoiesis
– PHSC cells
– CFU-S
• CFU-GM
• CFU-B / CFU-E
• CFU-M
– LSC
• Erythropoeisis
– Proerythroblast reticulocyte  erythrocyte
163
Physiology of RBCs
• Regulation of RBC production
– Erythropoietin (EPO) is secreted by the kidneys
in response to low oxygen levels in the blood
– EPO stimulates RBC production in the bone
marrow (fig 32-4)
• Factors that decrease oxygenation:
164
Physiology of RBCs
• Hemoglobin structure and function
– Carries oxygen (and some carbon dioxide) in
the blood
– Composition
• Heme – iron containing porphyrin ring structure
• Globin – polypeptide , alpha, beta, gamma or delta
– Most common types
• HbA – adult Hb = alpha2/beta2
• HbF – fetal Hb = alpha2/gamma2
165
Physiology of RBCs
• Iron Metabolism
– Iron is absorbed from GI tract
– Binds to apotransferrin to form transferrin
which carries the iron in the blood
– Iron is released to tissues which then binds to
apoferritin to form ferritin which is the storage
form of iron in cells.
– When ferritin stores are maximized, a insoluble
form of iron storage is hemosiderin
166
Physiology of RBCs
• Iron metabolism
– Iron is incorporated into heme (or other
compounds in cells requiring Fe)
• Iron loss
– In feces
– Bleeding
– Menstrual loss
167
Physiology of RBCs
• Red blood cell destruction
– Average life span = 120 days
– Metabolism of RBCs weakens so that:
•
•
•
•
Cell membrane becomes less pliable
Membrane transport of ions decreases
Heme iron goes into the ferric form
Oxidation of proteins
– RBCs rupture in the peripheral circulation or especially
in the spleen
• Kupffer cells phagocytose the damaged RBCs
• Hemoglobin is broken down into heme and globin which then
break down in to bilirubin and amino acids respectively
168
Introduction to the Anemias
• Definition – deficiency of hemoglobin
• Classification based on RBC size
– Normocytic
– Macrocytic
– Microcytic
• Classification based on hemoglobin content:
– Normochromic
– hypochromic
169
Introduction to the Anemias
• Hemorrhagic anemia
– Normocytic, normochromic
• Aplastic anemia
– Generally normocytic, normochromic
• Megaloblastic anemias
–
–
–
–
Macrocytic, normochromic
Anemia of folate deficiency
Anemia of B12 deficiency
Pernicious anemia
170
Introduction to the Anemias
• Hemolytic Anemias
–
–
–
–
Normocytic, normochromic
Hereditary spherocytosis
Sickle cell anemia
Erythroblastosis fetalis
• Anemia of iron deficiency
– Microcytic, hypochromic
171
Introduction to the Anemias
• Clinical findings
– Signs
• Low hematocrit
• Low hemoglobin
• Low RBC count
– Symptoms
•
•
•
•
Fatigue
Headache
Weakness
dizziness
172
Polycythemias
• Definition – high RBC count
• Causes
– Secondary polycythemia – due to high altitudes
or secondary to cardiac failure
– Primary polycythemia – polycythemia vera –
overproduction of RBCs in the bone marrow
due to genetic aberration
173
Hemostasis / Blood Coagulation
• Hemostasis = prevention of blood loss
• Steps of hemostasis
– Vascular spasm – constriction of blood vessels
reduces the rate of blood loss. Spasm is due to
pain, vascular wall damage, or thromboxane A2
– Platelet plug formation – activated platelets
form a weak plug
– Fibrin clot formation (coagulation) – a series of
clotting factors are involved in forming the clot.
174
Hemostasis / Blood Coagulation
• Platelet characteristics
–
–
–
–
Formed in bone marrow from megakaryocytes
Platelets contain actin and myosin
Platelets store calcium
They synthesize ATP, ADP, prostaglandins, fibrinstabilizing factor, thromboxane A2, and growth factors
– Have surface glycoproteins that stick to exposed
collagen
– Life span = 12 days
175
Hemostasis / Blood Coagulation
• Primary hemostasis – platelet plug formation
• Events occurring when platelets encounter
damaged blood vessel wall:
– Platelets swell and send out pseudopods that stick to the
vessel wall
– Contractile proteins contract to cause release of factors
including ADP and thromboxane A2; these factors
activate other platelets, and promote vascular spasm.
– Newly activated platelets stick to the growing plug.
176
Hemostasis / Blood Coagulation
Secondary hemostasis (coagulation, clot formation)
Platelet plugs are strengthened by the clotting process
• Clotting factors:
–
–
–
–
–
–
* I – fibrinogen
* II – prothrombin
* III – tissue factor
* IV – calcium
V – labile factor
VI – obsolete factor
– VII – stable factor
– * VIII – anti-hemophelia
factor
– IX – Christmas factor
– X – Stuart-Prower factor
– XI – Plasma thromboplastin
– XII – Hageman Factor
– * XIII – fibrin stabilizing
factor
177
Hemostasis / Blood Coagulation
• Clotting Cascade:
– Intrinsic pathway
extrinsic pathway
common pathway
– Common pathway (fig 36-2)
– Intrinsic pathway (fig 36-4)
– Extrinsic pathway (fig 36-3)
178
Hemostasis / Blood Coagulation
• Clot retraction – contraction of platelets tighten
the clot and pull the edges of the wound together.
• Prevention of unwanted clotting
– Intact blood vessel wall
– Glycocalyx – repels platelets and clotting factors
– Thrombomodulin – inhibits thrombin, and activates the
anticoagulant “protein C” which in turn inactivates
factors V and VIII
179
Hemostasis / Blood Coagulation
• Anticoagulants – limits the size of the clot
– Antithrombin – binds to thrombin
– Heparin – binds with antithrombin
• Lysis of blood clots
– Plasminogen
• Is converted to plasmin by plasminogen activator
which is gradually released by damaged tissues
• Plasmin digests the clot
180
Bleeding disorders
• Vitamin K deficiency – factors II, VII, IX, and X
require vitamin K for their synthesis by the liver
• Liver damage/disease – the liver is the source of
many clotting factors
• Hemophelia – caused by inheritance of a faulty
factor VIII gene. It is an X-linked trait.
• Thrombocytopenia – lack of platelets
(thrombocytopenic purpura = red spots visible on
the skin)
181
Thrombus and embolus
formation
• Thrombi are abnormal clots that form on
roughened endothelial surfaces
(atherosclerosis, infection, trauma)
• Emboli are thrombi that have broken loose
from their attachment and may lodge
elsewhere in the circulation
• Unwanted clots may be dissolved clinically
by administering plasminogen activator.
182
Review of Lung Anatomy
• Respiratory tree
–
–
–
–
–
–
–
–
–
–
larynx
Trachea – supplies both lungs
Primary bronchi – supplies each lung
Secondary bronchi – supplies each lobe
Tertiary bronchi – supplies each bronchopulmonary
segment (lobule)
Bronchioles
Terminal bronchioles
Respiratory bronchiole (capable of gas exchange)
Alveolar ducts (capable of gas exchange)
Alveolar sacs with alveoli (capable of gas exchange)
183
Pulmonary Ventilation
• Muscles of inspiration (active)
–
–
–
–
–
Diaphragm
External intercostals
Sternocleidomastoid
Serratus anterior
Scalenus muscles
• Muscles of expiration (only needed for forceful
expiration)
• Rectus abdominus
• Internal intercostals
184
Pulmonary ventilation
• Inspiration is due to muscle contraction
which increases thoracic cage size.
• The compliant lungs inflate due to the
negative pressure created in the pleural
cavity
• Expiration is due to the elasticity of the
thoracic soft tissue and the lungs
themselves.
185
Pulmonary ventilation
• Alveoli contain type II pneumocytes that
secrete pulmonary surfactant that breaks
surface tension of the fluid layer lining the
alveolar walls.
• Premature babies lack sufficient surfactant
and therefore develop respiratory distress
syndrome
186
Pulmonary volumes
• Tidal volume
• Inspiratory reserve volume
• Expiratory reserve volume
• Residual volume
187
Pulmonary capacities
• Capacities include more than one
pulmonary volume.
–
–
–
–
Inspiratory capacity
Functional residual capacity
Vital capacity
Total lung capacity
• Minute respiratory volume =
tidal volume X respiratory rate
188
Alveolar ventilation
• The rate at which new air reaches the gas
exchange surfaces. Actually, inspired air
rarely reaches beyond the terminal
bronchioles. New air reaches the gas
exchange surfaces by diffusion.
189
Dead air space
• Air that fills the respiratory passageways
that are not capable of gas exchange
– Anatomic dead air space – trachea  terminal
bronchioles
– Alveolar dead air space – damaged or otherwise
non-functional surfaces that no longer exchange
gas.
– Physiological dead air space – the sum of the
above
190
Alveolar Ventilation Rate
• Total volume of new air entering the alveoli
each minute:
Va = freq (Vt – Vd)
Va = alveolar ventilation rate
freq = respiration rate
Vt = tidal volume
Vd = physiologic dead air space
191
Respiratory Physiology
• Sympathetic discharge – causes bronchiolar
dilation
• Parasympathetic discharge – causes bronchiolar
constriction
• Cough reflex – irritation to bronchi and trachea 
afferent neurons (vagus)  medulla  efferent
neurons to muscles of epiglottis and abdomen
• Sneeze reflex – irritation to nasal passageways 
afferent neurons (trigeminal)  medulla 
efferent neurons to muscles of the uvula and
abdomen.
192
Nasal function
• The nose is a built in air conditioner.
– Air is warmed
– Air is humidified
– Air is partially filtered
193
Vocalization
• Speech involves:
– Respiratory system
– Cerebral cortex
– Phonation, resonance, and articulation structures
• Mechanical functions:
– Phonation – larynx; vocal cords
– Resonance – mouth, nose, sinuses, pharynx, chest
cavity
– Articulation – lips, tongue, soft palate
194
Blood supply to the lungs
• Pulmonary trunk  L and R pulmonary artery –
supplies each lung with deoxygenated blood from
the right ventricle.
• Bronchial vessels – originate from the systemic
arterial circulation (aorta) bringing oxygenated
blood to lung supportive structures, larger bronchi
etc.
• Pulmonary veins – 2 left and 2 right pulmonary
veins drain oxygenated blood from the lungs into
the left atrium.
195
Blood supply to the lungs
• Pulmonary arterial pressure
– Systolic – 25 mm Hg
– Diastolic – 8 mm Hg
– Mean pulmonary arterial pressure – 15 mm Hg
• Control of pulmonary blood flow
distribution – oxygen concentration effects
on vascular resistance.
196
Pressure Gradients and regional
pulmonary blood flow
• The pulmonary pressures in the upper portion of
the lung of a standing person is 23 mm Hg less
than the pulmonary pressure at the lower part of
the lung.
• Zones of pulmonary blood flow – effects of
hydrostatic pressure (fig 38-4)
– Zone 1 – no blood flow (abnormal)
– Zone 2 – intermittent blood flow (at apices)
– Zone 3 – continuous blood flow (middle and lower
lungs)
197
Pulmonary circulation response
to exercise
• The increased cardiac output during
exercise is accommodated by the pulmonary
circulation:
– Increasing the number of open capillaries
– Distending already open capillaries
– Low to moderate increase in pulmonary arterial
pressure
198
Pulmonary Capillary Dynamics
• See table p. 448
• As compared with systemic capillary
dynamics:
– Capillary pressure in lungs is lower
– Interstitial fluid pressure in lung is more
negative
– Interstitial osmotic pressure is lung is greater
199
Pulmonary Edema
• Any factor that increases the interstitial
fluid pressure, or capillary permeability in
the lungs
– Left heart failure
– Infections
– Breathing noxious fumes
200
Gas Exchange
• Gas pressures:
– Pressure is directly proportional to the concentration of
gas molecules in a system
– Gases in breathed air are mainly oxygen, nitrogen,
carbon dioxide, and water vapor.
– Partial pressures: the total pressure exerted by a mixture
of gases is equal to the sum of the individual pressures
of each gas.
– Partial pressures in water and tissue fluid is determined
by gas concentration and solubility in the water or
tissue fluid
– Carbon dioxide is more soluble in water than oxygen.
201
Composition of Air
• See table 39-1
• Atmospheric air – air in the environment
• Humidified air – air in anatomic dead air
space
• Alveolar air – air in gas exchange areas
• Expired air – air as it exits the body
• Note the significant CHANGES in partial
pressures of each gas.
202
Alveolar air
• Oxygen concentration in the alveoli is dependant
on:
– Rate of absorption of oxygen into the blood
– Rate of entry of new oxygen into the alveoli via
ventilation
• Carbon dioxide concentration in the alveoli is
dependant on:
– Rate of excretion of CO2 from the blood
– Rate of removal of CO2 from the alveoli via ventilation
• Generally it takes ~ 16 breaths to totally replace
alveolar air.
203
Respiratory membrane
• The structures in between the alveolar space and
the lumen of the capillary.
• 0.2 – 0.6 micrometers in thickness
• Layers of the respiratory membrane
–
–
–
–
–
–
Fluid layer
Alveolar epithelium
Epithelial basement membrane
Thin interstitial space
Capillary basement membrane
Capillary endothelium
204
Capillary membrane
• The rate of diffusion of gases through the
respiratory membrane depends on
–
–
–
–
Thickness
Surface area
Diffusion coefficient of the gas
Pressure difference across the membrane
205
Movement of Respiratory gases
• See handout
– Gas concentrations equilibrate between the
alveolar air and pulmonary capillary as blood
passes through the lung
– Gas concentrations equilibrate between the
systemic capillaries and the interstitial fluid as
blood passes through the tissues.
206
Gas exchange at the tissue level
• An increase in blood flow through a tissue will
increase PO2 and decrease PCO2 in the interstitial
fluid.
• An increase in tissue metabolism will decrease
PO2 and increase PCO2 in the interstitial fluid.
• Recall that normally, as tissue metabolism
changes, so does blood flow (autoregulation)
207
Transport of O2 in the blood
• Oxygen-hemoglobin dissociation curve (fig
40-8)
• Bohr effect (fig 4-10)
–
–
–
–
pH
CO2
Temperature
BPG (bisphosphoglycerate)
208
Transport of CO2 in the blood
• Dissolved CO2 ~ 10%
• Bicarbonate ~ 70%
• Carbaminohemoglobin ~ 20%
209
Regulation of Respiration
• Respiratory Center
– Dorsal respiratory group (tractus solitarius)
• Receives sensory input from CN IX and X from peripheral
chemoreceptors and baroreceptors
• Efferents stimulate inspiration (ramp signal)
– Ventral respiratory group (nucleus ambiguus)
• Function only in heavy ventilation and controls both
inspiration and expiration
– Pneumotaxic center (nuceleus parabrachialis)
• Controls duration of inspiration set by the dorsal respiratory
group therefore influencing rate and depth of breathing
– Hering-Breuer reflex – prevents excessive lung
inflation
210
Chemical Control of Respiration
• Hydrogen ions and CO2 – effects
respiratory center directly to increase
respiratory rate
• Oxygen – indirect effect via carotid and
aortic body chemoreceptors.
211
Respiratory Insufficiency
• Obstructive lung diseases:
– Increased resistance to air flow as a result of
reduction in the diameter of airways. The
increased resistance to air flow can result from
processes within the lumen, wall, or supporting
structures of the lung.
– Examples – asthma, emphysema
– Tend to have increased TLC, RV, and decreased
VC.
– Characterized by “air trapping”
212
Respiratory Insufficiency
• Restricted (constricted) lung diseases:
– Inflammation or scarring of lung and airway
tissues. Associated with increased lung elastic
recoil and decreased compliance
– Examples – pneumonia, tuberculosis,
atelactasis
– Tend to have decreased TLC, RV and VC
– Have trouble with inflation
213
Spirometry
• Maximal expiratory flow (MEF) – measured as a
rate of air flow (L/min) during a forced maximal
expiration following a maximal inspiration to total
lung capacity (fig 42-1)
• Forced vital capacity (FVC) – measurement of
lung volume (L) produced by a maximal forced
expiration following a maximal inspiration to total
lung capacity
• Forced expiratory volume (FEV1) – measurement
of the volume of air (L) expired during the first
second of maximal forced expiration following a
maximal inspiration.
214
• FEV1 / FVC X 100 = 80% normally
Terminology
• Hypoxia – lack of oxygen. Can be caused by
inadequate delivery of oxygen to tissues by the
respiratory system, or by a deficient utilization of
oxygen by the cells
• Hypercapnia – excess CO2 in the body fluids
commonly due to hypoventilation or diminished
blood flow
• Cyanosis – blueness of the skin caused by excess
deoxygenated blood in the capillaries
• Dyspnea – mental anguish associated with the
inability to ventilate enough to satisfy the demand
for oxygen (air hunger)
215
Chronic Pulmonary emphysema
• Obstructive lung disease
• Destruction of alveolar walls and
connective tissue causing permanent
enlargement of the airspaces distal to the
terminal bronchioles.
• Chronic obstruction of airways (mucus,
edema, infection) due to chronic bronchitis
• Due to cigarette smoking
216
Chronic Pulmonary emphysema
• Symptoms
–
–
–
–
–
–
–
–
Decreased breath sounds
Tachycardia and pulmonary hypertension
Hyperinflation of lungs (barrel chest)
TLC and RV are increased (air trapping)
VC is decreased
FVC and FEV1 are decreased
Hypoxia and hypercapnia
polycythemia
217
Pneumonia
• Restrictive lung disease
• Inflammation of the lung in which the
alveoli become filled with fluid and blood
cells. Usually due to infection with
pneumococci bacteria
• Pulmonary edema (increases diffusion
distance in the respiratory membrane)
218
Pneumonia
• Symptoms
–
–
–
–
–
Fever
Cough (productive)
Hypoxia and hypercapnia
TLC, RV, VC are reduced
Decreased ventilation / perfusion ratio
219
Atelectasis
• Restrictive
• Collapsed lung (alveoli) due to total airway
obstruction, lack of surfactant, or pneumothorax
• Symptoms:
–
–
–
–
–
Chest tightness, pain
Dyspnea
Hypoxia and hypercapnia
TLC, RV and VC are decreased
FVC and FEV1 are decreased
220
Asthma
• Obstructive
• Bronchial hyper responsiveness to a variety
of allergens, chemicals, etc. producing
bronchoconstriction. Exercise and cold can
exacerbate asthma.
• Airway inflammation, hyper-secretion of
mucus
221
Asthma
• Symptoms
–
–
–
–
–
–
–
–
–
–
Cough
Wheezing
Dyspnea
Chest tightness
Reduced ventilation rate and tachycardia
TLC and RV are increased
VC is decreased
FVC and FEV1 are decreased
Hypercapnia and hypoxia
Respiratory acidosis
222
Tuberculosis
• Restricted
• Lung infection by the M. tuberculosis
bacilli, which causes scarring and
destruction of tissue
• Macrophages wall of lesion with fibrous
tissue reducing surface area and thickening
of the respiratory membrane
223
Tuberculosis
• Symptoms
– Cough (productive)
– Dyspnea
– TLC, VC, and RV are reduced
224
Exercise Physiology
• Muscle characteristics
– Strength
– Power
– Endurance
• Energy
– Phosphogen system
– Glycogen-lactic acid system
– Aerobic system
225
Exercise Physiology
• Recovery after exercise
– Oxygen debt
• Restore depleted body oxygen:
–
–
–
–
.5 L in lungs
.25 L in fluids
1 L in hemoglobin
.3 L in myoglobin
• Restore phosphogen system and lactic acid 9L
– Alactic acid vs. lactic acid O2 debt (fig 84-2)
– Restore glycogen stores in muscle (fig 84-3)
226
Exercise Physiology
• Diet and exercise (fig 84-4)
• Muscles
– Resistance training vs. no load training
– Fast twitch vs. slow twitch fibers
227