Circulation

1
Circulation

• The main function of the systemic circulation is
  to deliver adequate oxygen, nutrients to the
  systemic tissues and remove carbon dioxide
  other waste products from the systemic tissues
• The systemic circulation is also serves as a
  conduit for transport of hormones, and other
  substances and allows these substances to
  potentially act at a distant site from their
  production

2
Functional Parts

• systemic arteries
• designed to carry blood under high pressure out
  to the tissue beds
• arterioles pre capillary sphincters
• act as control valves to regulate local flow
• capillaries- one cell layer thick
• exchange between tissue (cells) blood
• venules
• collect blood from capillaries
• systemic veins
• return blood to heart/dynamic storage

3
Basic theory of circulatory function

• Blood flow is proportional to metabolic demand
• Cardiac output controlled by local tissue flow
• Arterial pressure control is independent of local
  flow or cardiac output

4
Characteristics of Vessels

• Components
• Endothelium- one layer exists in all vessels
• Elastic tissue (1)
• Smooth muscle (2)
• Fibrous tissue (3)
• Relative composition
• Aorta 1gt3gt2
• typical artery 2gt1gt3
• vein 1 2 3
• capillary- only endothelium

5
Hemodynamics

• Flow
• Pressure gradient
• Resistance
• Ohms Law
• V IR (Analogous to ? P QR)

6
Flow (Q)

• The volume of blood that passes a certain point
  per unit time (eg. ml/min)
• Q velocity X cross sectional area
• At a given flow, the velocity is inversely
  proportional to the total cross sectional area
• Q ? P / R
• Flow is directly proportional to ? P and
  inversely proportional to resistance (R)

7
Pressure gradient

• Driving force of blood
• difference in pressure between two points
• proportional to flow (Q)
• At a given Q the greater the drop in P in a
  segment or compartment the greater the resistance
  to flow.

8
Resistance

• R 8?l/? r4
• ? viscosity, l length of vessel, r radius
• Parallel circuit
• 1/RT 1/R1 1/R2 1/R3 1/RN
• RT lt smallest individual R
• Series circuit
• RT R1 R2 R3 RN
• RT sum of individual Rs
• The systemic circulation is predominantly a
  parallel circuit

9
Advantages of Parallel Circuitry

• Independence of local flow control
• increase/decrease flow to tissues independently
• Minimizes total peripheral resistance (TPR)
• Oxygen rich blood supply to every tissue

10
Viscosity

• Internal friction of a fluid associated with the
  intermolecular attraction
• Blood is a suspension with a viscosity of 3
• most of viscosity due to RBCs
• Plasma has a viscosity of 1.5
• Water is the standard with a viscosity of 1
• With blood, viscosity 1/? velocity

11
Viscosity considerations at microcirculation

• velocity decreases which increases viscosity
• due to elements in blood sticking together
• cells can get stuck at constriction points
  momentarily which increases apparent viscosity
• fibrinogen increases flexibility of RBCs
• in small vessels cells line up which decreases
  viscosity and offsets the above to some degree
  (Fahaeus-Lindquist)

12
Hematocrit

• of packed cell volume (10 RBCs)
• Normal range 38-45

13
Laminar vs. Turbulent Flow

• Streamline
• silent
• most efficient
• normal

• Cross mixing
• vibrational noise
• least efficient
• frequently associated with vessel disease (bruit)

14
Reynolds number

• Probability statement for turbulent flow
• The greater the R, the greater the probability
  for turbulence
• R v D ?/?
• v velocity, D tube diameter, ? density,
  ? viscosity
• If R lt 2000 flow is usually laminar
• If R gt 3000 flow is usually turbulent

15
Doppler Ultrasonic Flow-meter

• Ultrasound to determine velocity of flow
• Doppler frequency shift ? function of the
  velocity of flow
• RBCs moving toward transmitter, compress sound
  waves, ? frequency of returning waves
• Broad vs. narrow frequency bands
• Broad band is associated with turbulent flow
• narrow band is associated laminar flow

16
Determination of Flow

• Determination of Cardiac Output
• Fick principal
• Indicator dilution
• Determination of vessel flow
• Venous occlusion plesthymography
• Momentary limb blood flow
• Doppler ultrasonic flowmeter
• Vascular flow cuffs

17
Fick Principal

• Blood flow to a tissue/organ
• 3 port system
• Input blood concentration of substance x
• Output blood concentration of substance x
• Addition/removal of substance x from tissue
• Flow amount of substance per min
  AV difference
• See figure 20-18 (Guyton)

18
Indicator dilution

• Based on conservation of mass
• CO mg dye injected X 60
• ------------------------------------------
  ---------- ave conc of dye X duration of curve
  (sec)
• in each ml for duration
• of the curve
• See figure 20-19 (Guyton)

19
Distensibility Vs. Compliance

• Distensibility is the ability of a vessel to
  stretch (distend)
• Compliance is the ability of a vessel to stretch
  and hold volume

20
Distensibility Vs. Compliance

• Distensibility ? Vol/? Pressure X Ini. Vol
• Compliance ? Vol/? Pressure
• Compliance Distensibility X Initial Vol.
  

21
Volume-Pressure relationships

• A ? volume ? ? pressure
• In systemic arteries a small ? volume is
  associated with a large ? pressure
• In systemic veins a large ? volume is associated
  with a small ? pressure
• Veins are about 8 X more distensible and 24 X
  more compliant than systemic arteries
• Wall tone 1/? compliance distensibility

22
Volume-Pressure relationships
23
Control of Blood Flow (Q)

• Local blood flow is regulated in proportion to
  the metabolic demand in most tissues
• Short term control involves vasodilatation
  vasoconstriction of precapillary resist. vessels
• arterioles, metarterioles, pre-capillary
  sphincters
• Long term control involves changes in tissue
  vascularity
• formation or dissolution of vessels
• vascular endothelial growth factor angiogenin

24
Role of arterioles in control of flow

• Arterioles act as an integrator of multiple
  inputs
• Arterioles are richly innervated by SNS
  vasoconstrictor fibers and have alpha receptors
• Arterioles are also effected by local factors
  (e.g.)vasodilators, circulating substances

25
Local Control of Flow (short term)

• Involves vasoconstriction/vasodilatation of
  precapillary resistance vessels
• Local vasodilator theory
• Active tissue release local vasodilator
  (metabolites) which relax vascular smooth muscle
• Oxygen demand theory (older theory)
• As tissue uses up oxygen, vascular smooth muscle
  cannot maintain constriction

26
Local Vasodilators

• Adenosine
• carbon dioxide
• adenosine phosphate compounds
• histamine
• potassium ions
• hydrogen ions
• PGE PGI series prostaglandins

27
Autoregulation

• The ability to keep blood flow (Q) constant in
  the face of a changing arterial BP
• Most tissues show some degree of autoregulation
• Q ? metabolic demand
• In the kidney both renal Q and glomerular
  filtration rate (GFR) are autoregulated

28
Control of Flow (long term)

• Changes in tissue vascularity
• On going day to day reconstruction of the
  vascular system
• Angiogenesis-production of new microvessels
• arteriogenesis
• shear stress caused by enhanced blood flow
  velocity associated with partial occlusion
• Angiogenic factors
• small peptides-stimulate growth of new vessels
• VEGF (vascular endothelial growth factor)

29
Changes in tissue vascularity

• Stress activated endothelium up-regulates
  expression of monocyte chemoattractant protein-1
  (MCP-1)
• attraction of monocytes that invade arterioles
• other adhesion molecules growth factors
  participate with MCP-1 in an inflammatory
  reaction and cell death in potential collateral
  vessels followed by remodeling development of
  new enlarged collateral arteries arterioles

30
Changes in tissue vacularity (cont.)

• Hypoxia causes release of VEGF
• enhanced production of VEGF partly mediated by
  adenosine in response to hypoxia
• VEGF stimulates capillary proliferation and may
  also be involved in development of collateral
  arterial vessels
• NPY from SNS is angiogenic
• hyperactive SNS may compromise collateral blood
  flow by vasoconstriction
• Cancer and angiogenesis

31
Vasoactive Role of Endothelium

• Release prostacyclin (PGI2)
• inhibits platelet aggregation
• relaxes vascular smooth muscle
• Releases nitric oxide (NO) which relaxes vascular
  smooth muscle
• NO release stimulated by
• shear stress associated with increased flow
• acetylcholine binding to endothelium
• Releases endothelin endothelial derived
  contracting factor
• constricts vascular smooth muscle

32
Microcirculation

• Capillary is the functional unit of the
  circulation
• bulk of exchange takes place here
• Vasomotion-intermittent contraction of
  metarterioles and precapillary sphincters
• functional Vs. non functional flow
• Mechanisms of exchange
• diffusion
• ultrafiltration
• vesicular transport

33
Oxygen uptake/utilization

• the product of flow (Q) times the
  arterial-venous oxygen difference
• O2 uptake (Q) (A-V O2 difference)
• Q300 ml/min
• AO2 .2 ml O2/ml blood
• VO2 .15 ml O2/ml blood
• 15 ml O2/ min (300 ml/min) (.05 mlO2/ml)

34
Functional Vs. Non Functional Flow

• Functional or Nutritive flow (Q) is associated
  with increased oxygen uptake/utilization
• x causes Q to ? from 300 to 600 ml/min, A-V O2
  stays at .05 ml O2/ml, O2 uptake has ? from 15 to
  30 ml O2/min, ?? in Q is functional (nutritive)
  because of ? O2 uptake
• y causes Q to ? from 300 to 600 ml/min, but A-V
  O2 ? from .05 to .025 ml O2/ml, O2 uptake, is
  still 15 ml O2/min ?? in Q is nonfunctional (non
  nutritive) because O2 uptake has not changed.
• Non nutritive flow increases is associated with
  shunting of blood through a bed

35
Capillary Exchange

• Passive Diffusion
• permeability
• concentration gradient
• Ultrafiltration
• Bulk flow through a filter (capillary wall)
• Starling Forces
• Hydrostatic P
• Colloid Osmotic P
• Vesicular Transport
• larger MW non lipid soluble substances

36
Ultrafiltration

• Hydrostatic P gradient (high to low) favors
  filtration
• Capillary HP averages 17 mmHg
• Interstitial HP averages -3 mmHg
• Colloid Osmotic P (low to high) favors
  reabsorption
• Capillary COP averages 28 mmHg
• Interstitial COP averages 9 mmHg
• Net Filtration P (CHP-IHP)-(CCOP-ICOP)
• 1 20 -
  19

37
Colloid Osmotic Considerations

• The colloid osmotic pressure is a function of the
  protein concentration
• Plasma Proteins
• Albumin (75)
• Globulins (25)
• Fibrinogen (lt1)
• Calculated Colloid Effect is 19 mmHg
• Actual Colloid Effect is 28 mmHg
• Discrepancy is due to the Donnan Effect

38
Donnan Effect

• Increases the colloid osmotic effect
• Large MW plasma proteins (1o albumen) carries
  negative charges which attract ions (1o Na)
  increasing the osmotic effect by about 50

39
Effect of Ultrastructure of Capillary Wall on
Colloid Osmotic Pressure

• Capillary wall can range from tight junctions
  (e.g. blood brain barrier) to discontinuous (e.g.
  liver capillaries)
• Glomerular Capillaries in kidney have filtration
  slits (fenestrations)
• Only that protein that cannot cross capillary
  wall can exert osmotic pressure

40
Reflection Coefficient

• Reflection Coefficient expresses how readily
  protein can cross capillary wall
• ranges between 0 and 1
• If RC 0
• All colloid proteins freely cross wall, none are
  reflected, ?no colloid effect
• If RC 1
• All colloid proteins are reflected, none cross
  capillary wall, ? full colloid effect

41
Lymphatic system

• Lymph capillaries drain excess fluid from
  interstitial spaces
• No true lymphatic vessels found in superficial
  portions of skin, CNS, endomysium of muscle,
  bones
• Thoracic duct drains lower body left side of
  head, left arm, part of chest
• Right lymph duct drains right side of head, neck,
  right arm and part of chest

42
CNS-modified lymphatic function

• No true lymphatic vessels in CNS
• Perivascular spaces contain CSF communicate
  with subarachnoid space
• Plasma filtrate escaped substances in
  perivascular spaces returned to the vascular
  system in the CSF via the arachnoid villi which
  empties into dural venous sinuses
• Acts a functional lymphatic system in CNS

43
Formation of Lymph

• Excess plasma filtrate-resembles ISF from tissue
  it drains
• Protein ? 3-5 gm/dl in thoracic duct
• liver 6 gm/dl
• intestines 3-4 gm/dl
• most tissues ISF 2 gm/dl
• 2/3 of all lymph from liver intestines
• Any factor that ? filtration and/or ?
  reabsorption will ? lymph formation

44
Rate of Lymph Formation/Flow

• Thoracic duct- 100 ml/hr.
• Right lymph duct- 20 ml/hr.
• Total lymph flow- 120 ml/hr (2.9 L/day)
• Every day a volume of lymph roughly equal to your
  entire plasma volume is filtered

45
Function of Lymphatics

• Return lost protein to the vascular system
• Drain excess plasma filtrate from ISF space
• Carry absorbed substances/nutrients (e.g.
  fat-chlyomicrons) from GI tract
• Filter lymph (defense function) at lymph nodes
• lymph nodes-meshwork of sinuses lined with tissue
  macrophages (phagocytosis)

46
Arterial blood pressure

• Arterial blood pressure is created by the
  interaction of blood with vascular wall
• Art BP volume of blood interacting with the
  wall
• inflow (CO) - outflow (TPR)
• Art BP CO X TPR
• Greater than 1/2 of TPR is at the level of
  systemic arterioles

47
Systole

• During systole the left ventricular output (SV)
  is greater than peripheral runoff
• Therefore total blood volume rises which causes
  arterial BP to increase to a peak (systolic BP)
• The arteries are distended during this time

48
Diastole

• While the left ventricle is filling, the arteries
  now are recoiling, which serves to maintain
  perfusion to the tissue beds
• Total blood volume in the arterial tree is
  decreasing which causes arterial BP to fall to a
  minimum value (diastolic BP)

49
Hydraulic Filtering

• Stretch (systole) recoil (diastole) of the
  arterial tree that normally occurs during the
  cardiac cycle
• This phenomenon converts an intermittent output
  by the heart to a steady delivery at the tissue
  beds saves the heart work
• As the distensibility of the arterial tree ? with
  age, hydraulic filtering is reduced, and work
  load on the heart is increased

50
Systolic Blood Pressure

• The maximum pressure in the systemic arteries
• Pressure peaks as blood is ejected from the left
  ventricle into the aorta
• Inflow volume from the LV typically occurs at a
  faster rate then peripheral runoff out the
  arterial tree during systole causing arterial P
  to ?

51
Diastolic Blood Pressure

• The minimum pressure in the systemic arteries
• How low the pressure falls is dependent on 2
  factors
• Cycle length (CL) inversly proportional to DBP
• ? CL will ?DBP
• Total peripheral resistance (TPR) proportional to
  DBP
• ? TPR will ? DBP
• During exercise DBP may not change much due to ?
  CL is offset by ? in TPR.

52
Mean Arterial Blood Pressure

• The mean arterial pressure (MAP) is not the
  arithmetical mean between systole diastole
• determined by calculating the area under the
  curve, and dividing it into equal areas
• MAP 1/3 Pulse Pressure DBP (approximation)

53
Effects of SNS

• Most post-ganglionic SNS terminals release
  norepinephrine.
• The predominant receptor type is alpha (?)
• ? response is constriction of smooth muscle
• Constriction of arterioles reduce blood flow and
  help raise arterial blood pressure (BP)
• Constriction of arteries raise arterial BP
• Constriction of veins increases venous return

54
SNS (cont)

• SNS causes widespread vasoconstriction causing
  ? blood flow with 3 exceptions
• Brain
• arterioles weakly innervated with SNS
• Lungs
• arterioles weakly innervated with SNS
• Heart
• direct vasoconstrictor effects over-ridden by SNS
  induced increase in cardiac activity which causes
  release of local vasodilators (adenosine)

55
Critical Closing Pressure

• As arterial pressure falls, there is a critical
  pressure below which flow ceases due to the
  closure of the arterioles.
• This critical luminal pressure is required to
  keep arterioles from closing completely
• vascular tone is proportional to CCP
• e.g. SNS of arterioles ? CCP

56
Mean Circulatory Filling Pressure

• If cardiac output is stopped, arterial pressure
  will fall and venous pressure will rise
• MCFP equilibration pressure where arterial BP
  venous BP
• equilibration pressure may be prevented by
  closure of the arterioles (critical closing
  pressure)
• responsible for pressure gradient driving
  peripheral venous return

57
Vascular Function Curves

• At a given MCFP as Central Venous Pressure ?,
  venous return ?
• If MCPF CVP venous return goes to 0

58
Vascular function curve
59
Cardiac Function Curve

• As central venous pressure increases, cardiac
  output increases due to both intrinsic
  extrinsic effects

60
Cardiac Function Curve
61
Central Venous Pressure

• The pressure in the central veins (superior
  inferior vena cava) at the entry into the right
  atrium.
• Central venous pressure right atrial pressure

62
Vasomotor center

• Collection of neurons in the medulla pons
• Four major regions
• pressor center- increase blood pressure
• depressor center- decrease blood pressure
• sensory area- mediates baroreceptor reflex
• cardioinhibitory area- stimulates X CN

63
Vasomotor Center

• Pressor Center (Vasoconstrictor Center C1 )
• anterolateral portions of upper medulla
• norepinephrine projections to IML horn cells
  (pre-ganglionic SNS)
• effects
• vasocontriction
• stimulate cardiac activity
• tonically active exciting SNS outflow

64
Vasomotor Center

• Depressor Center (Vasodilator area A1)
• fibers project into and inhibit pressor center
• anterolateral lower medulla oblongata
• effects (by inhibiting pressor center)
• vasodilatation
• decreased cardiac activity

65
Vasomotor Center

• Sensory Area A2
• posterolateral portions of pons and medulla
• in nucleus tractus solitarius
• receive input primarily from IX X CN
• outputs to both pressor depressor centers
• mediates baroreceptor reflex
• inhibits pressor center
• lowers blood pressure

66
Vasomotor Center

• Cardioinhibitory Area
• located medially next to dorsal motor nucleus of
  vagus (DMNV)
• transmits impulses into DMNV inhibiting heart
  activity

67
Vasomotor Center

• Sympathetic vasoconstrictor tone
• due to pressor center input
• 1/2 to 2 IPS
• maintains normal arterial blood pressure

68
Control of Blood Pressure

• Rapid short term control involves the nervous
  systems effect on vascular smooth muscle
• Long term control is dominated by the kidneys-
• Renal-body fluid balance

69
Control of Blood Pressure

• Concept of Contents vs. Container
• Contents
• blood volume
• Container
• blood vessels
• Control of blood pressure is accomplished by
  either affecting vascular tone or blood volume

70
Baroreceptors

• Spray type nerve endings in vessel walls
• Especially abundant in
• Carotid Sinus
• Arch of Aorta
• Stimulated when stretched
• Inhibits Pressor Center via IX X CN NTS
• Net Effects
• vasodilatation
• decreased cardiac output

71
Baroreceptors (cont)

• Carotid sinus reflex
• more sensitive to changing P than static P
• buffer function
• buffer ? in BP to ? in blood volume
• During normal cardiac cycle
• Buffer ? in BP due to ? in body position
• Eg. Lying to standing position
• lack of long term control due to adaptation
• resetting within 1-2 days

72
Low Pressure Baroreceptors

• Located in atrial walls pulmonary arteries
• augment arterial baroreceptors
• minimize arterial pressure changes in response to
  blood volume changes

73
Infusion Study
74
Stretch on Atrial Wall

• Baroreceptor reflex- low pressure
• decreased heart rate
• increased urine production
• decreased SNS in renal nerves
• decreased secretion of ADH
• Bainbridge reflex- increase heart rate
• Release of Atrial Natriuretic Peptide
• dirurectic, natriuretic, vasodilator

75
Renal-Body Fluid System

• Arterial Pressure (AP) Control
• Increased ECF will cause AP to rise
• In response the kidneys excrete excess ECF

76
Determinants of long term AP

• The degree of shift of the renal output curve for
  water and salt
• The level of the water and salt intake line
• Increased total peripheral resistance will not
  create a long term elevation of BP if fluid
  intake and renal function do not change

77
The Kidney

• Afferent arterioles supply the glomerular
  capillaries where filtration takes place
• Efferent arterioles drain the glomerular
  capillaries and give rise to the peritubular
  capillaries where reabsorption takes place
• vasa recti
• specialized peritubular capillaries associated
  with juxtamedullary nephrons

78
Autoregulation at the kidney

• Most autoregulation of both renal blood flow and
  glomerular filtration takes place at the afferent
  arteriole
• Normal glomerular filtration rate is about 100
  ml/min
• Normal renal blood flow is about 1.25 L/min (25
  of Cardiac Output)

79
Role of afferent efferent arterioles in
autoregulation

• In kidney
• constriction of afferent arterioles will decrease
  both renal Q and GFR
• constriction of efferent arterioles will decrease
  renal Q but increases GFR by creating back
  pressure
• therefore in the face of a rising arterial BP
  constriction of the afferent arterioles alone can
  autoregulate both Q and GFR (within limits)

80
Renal control of blood pressure

• When the extracellular fluid levels rises, the
  arterial pressure rises
• The kidney excretes more fluid, thus bringing the
  pressure back to normal

81
Renal output curves

• Acute-effect of arterial pressure alone
• Chronic-effect of arterial pressure plus
• SNS
• Renin-angiotensin system
• Aldosterone
• ADH
• ANP

82
Hormones regulating RBF

• Decrease renal blood flow (RBF)
• norepinephrine
• epinephrine
• angiotensin II
• Increase renal blood flow (RBF)
• prostaglandins (E I)

83
Tubuloglomerular feedback

• Moniters NaCl in the Macula densa of the distal
  tubule
• ? NaCl in Macula densa renin release from the
  Juxtaglomerular (JG) cells
• ? renin? ? angiotensin II levels ? ? efferent
  arteriole resistance
• ? NaCl in Macula densa also causes dilatation of
  afferent arteriole

84
Renin-Angiotensin-Aldosterone System

• Source of renin
• Smooth muscle cells in afferent arteriole
  (primary)
• Synthesis, storage, release
• Stimulated by
• ? perfusion pressure
• SNS
• ? NaCl delivery to macula densa (distal tubule)
• Tubuloglomerular feedback
• Hormonal stimulation
• Thyroid hormone
• Growth hormone

85
Renin-Angiotensin-Aldosterone System (cont.)

• Renin is an enzyme the catalyses the fomation of
  Angiotensin I (10 amino acids) from
  angiotensinogen (liver)
• Angiotensin I ? Angiotensin II (8 aa)
• occurs primarily in lung via angiotensin
  converting enzyme associated with the pulmonary
  endothelium

86
Angiotensin II

• Functions
• Stimulates the adrenal cortex to secrete
  aldosterone
• Stimulates the release of ADH/vasopressin
• Stimulates the kidney
• Net effect of all of the above is to
• ? Na H2O excretion ? ? BP
• Also stimulates thirst/drinking behavior at the
  level of the hypothalamus

87
Generation of hypertension

• Tie off one renal artery
• development of systemic hypertension
• elevation of renin and angiotensin II
• no development of uremia
• Tie off one renal artery and remove kidney
• no development of hypertension or uremia
• Tie off and remove both kidneys
• development of both hypertension and uremia

88
Generation of Hypertension

• Hypertension generated by tying off a renal
  artery is called Goldblatt hypertensive model.
• One vs. Two kidney varieties
• One kidney variety, initially renin is high
• In the two kidney model the renin from the
  restricted kidney causes fluid retention of the
  good kidney

89
Role of breathing in BP control

• Slow breathing (6/min) ? arterial baroreflex
  sensitivity
• Beneficial effects of slow breathing (in CHF
  patients)
• ?resting oxygen saturation
• Improves ventilation/perfusion mismatching
• Improves exercise tolerance by ? sensation of
  dyspnea
• ?chemoreflex activation
• ?sympathetic activity
• ? SBP and DBP
• (circ. 2002105143-145)

90
Effect of antioxidants on BP

• Nitric oxide from the endothelium relaxes smooth
  muscle
• Nitric oxide is rapidly inactivated by superoxide
  radical
• Increasing antioxidants reduces the number of
  free radicals allowing nitric oxide effect to be
  longer lasting, lowering BP

91
Antioxidants

• Glutathione
• Melatonin
• Superoxide dismutase
• Beta-carotene
• Lutein

• Lycopene
• Selenium
• Vitamin A
• Vitamin C
• Vitamin E

92
Possible role of humoral substances in hypotension

• Serotonin may act at the CNS to inhibit reflex
  SNS activation
• Nitric oxide may act centrally to inhibit
  sympathetic nerve activity
• The above may promote bradycardia and hypotension

93
Circulatory Readjustments at Birth

• Increased blood flow through lungs liver
• pulmonary vascular resistance decreases
• decreased RVP, pulmonary arterial BP
• Loss of blood flow through the placenta
• doubles the systemic vascular resistance
• increased LAP, LVP, aortic BP
• Closure of Foramen Ovale, Ductus Arteriosis,
  Ductus Venosus

94
Circulatory Readjustments (cont)

• Closure of Foramen Ovale
• due to reversal of pressure gradient between RA
  and LA, flap closes
• Closure of Ductus Arteriosis
• Reversal of flow from aorta to pulmonary artery,
  and increased oxygen levels cause constriction of
  smooth muscle
• Closure of Ductus Venosus
• cause unknown
• allows portal blood to perfuse liver sinuses

95
Circulation in Fetus

• Right and Left Ventricle pump in parallel into
  the aorta
• Very little pulmonary blood flow
• Low pressure in aorta due to low TPR because of
  placenta-umbilical arteries
• Blood returning from the placenta via the
  umbilical veins bypass liver and flow directly
  into inferior VC via dutus venosus

96
Circulation in Fetus

• In the fetus there exsits two right to left
  shunts for blood to bypass the lungs
• Foramen Ovale shunts most blood returning to the
  the heart from the inferior vena cava to the left
  atrium
• Ductus Arteriosus shunts most blood returning to
  the heart from the superior vena cava to the aorta

97
Congenital Defects

• Patent Ductus Arteriosus
• creates a left to right shunt
• machinery murmur
• 1/3000
• Ventricular Septal Defect
• Transposition of Great Vessels
• Tetrology of Fallot

98
Tetrology of Fallot

• Right Ventricular Hypertrophy
• Large Ventricular Septal Defect
• Right Ventricular Outflow Obstruction
• Overriding Aorta
• Symptoms
• cyanosis
• dyspnea
• squatting in children for relief of dyspnea

99
CV changes during exercise
100
Exercise

• Greatest stress on the CV system
• Sympathetic nervous system orchestrates many of
  the changes associated with exercise
• Cardiac output is increased 5-6 fold
• Blood flow is shifted primarily from organs to
  active skeletal muscle

101
CV changes during exercise

• Cerebral cortical activation of the SNS
• SNS effects
• vasoconstriction of arterioles to ? flow to non
  active tissues (viscera)
• vasoconstriction of veins to ? MCFP which ?
  venous return
• stimulation of heart (? HR, SV) ? ? CO
• TPR ? due to vasodilatation in active muscle
• Increased O2 uptake which decreases VO2 ? ? AVO2
  difference (AO2 stays relatively constant

102
The role of the SNS

• SNS stimulation due to
• Cerebral cortex stimulation (central command)
• Reflex signals from active joint proprioceptors
  and muscle spindles
• Local chemoreceptor signals originating in the
  active muscle
• SNS effects
• Increased HR and SV (CO)
• Induces local metabolic vasodilatation at the
  heart

103
SNS effects (cont)

• SNS stimulation of pre-capillary resistance
  vessels (organs and inactive skeletal muscle)
  decreases blood flow
• SNS stimulation of veins causes constriction
  which mobilizes blood out of veins increasing
  venous return
• Redistribution of blood volume
• SNS stimulation of vascular smooth muscle in
  walls of arteries help maintain slightly
  increased blood pressure during exercise

104
Tissues that escape SNS vasoconstriction

• Heart
• SNS indirectly induces local vasodilatation by
  increasing cardiac muscle contractility and
  promoting the release of local vasodilators
  (overriding direct constrictor effect)
• Brain
• SNS stimulation induces a weak constrictor
  response that doesnt limit blood flow
• Lungs
• SNS stimulation induces a mild vasoconstriction
  that doesnt limit blood flow. Pulmonary blood
  flow CO

105
AP changes during exercise

• ? SBP due to the ? CO gt ? TPR (also ? SNS
  contributes to ?)
• ? DBP only slightly (and may ? )
• ? Pulse Pressure (?SBP gt ?DBP)
• PP SBP - DBP

106
? venous return during exercise

• SNS constriction of veins
• Venous Pump
• Intermittent skeletal muscle activity coupled
  with one way valves in veins
• Primarily occurs in lower extremities
• ? frequency depth of respiration
• increased cyclic negative thoracic pressure

107
Increased flow to active muscle

• Increased blood flow to the active muscle is NOT
  mediated by the SNS but by the local release of
  tissue metabolites in response to the increase in
  metabolism Local vasodilators (partial list)
• Adenosine
• CO2
• K
• Histamine
• Lactic acid

108
Blood Flow

• Rest CO 5.9 L/min
• Coronary-250 ml/min
• Brain-750 ml/min
• Organs-3100 ml/min
• Inactive muscle-650 ml/min
• Active muscle-650 ml/min
• Skin- 500 ml/min

• Exercise 24 L/min
• Coronary-1000 ml/min
• Brain-750 ml/min
• Organs-600 ml/min
• Inactive muscle-300 ml/min
• Active muscle-20,850 ml/min
• Skin- initially?, then ?as body temp ?

109
Effect of exercise on CV endpoints

• HR ? (60-180 b/min)
• SV ? to a point and then may ?
• CO ? (5-25 L/min)
• Systolic BP ?
• Diastolic BP ? (slightly)
• Mean arterial BP ? (slightly)
• Total peripheral resistance ?
• Oxygen consumption ? (.25-5.0 L/min)
• Arteriovenous oxygen difference ? (25-50)

110
VO2 Maximum

• The maximum volume of oxygen that one can take up
  from the lungs and deliver to the tissues/minute
• Can range from 1.5 L/min in a cardiac patient to
  3.0 L/min in a sedentary man to 6.0 L/min or
  greater in an endurance athlete
• Function of CO and AV O2 difference
• Proportional to increases in SV as training occurs

111
Oxygen Debt

• If energy (E) demands of exercise cannot be met
  by oxidative phosphorylation, O2 debt occurs.
• After completion of exercise, respiration remains
  elevated to repay the O2 debt.
• Extra O2 is used to
• Restore metabolite levels
• i.e. Creatine phosphate ATP
• Metabolize lactate generated by glycolysis
• O2 debt E consumed during exercise that E
  supplied by oxidative metabolism

112
Muscle metabolic systems in exercise

• The phosphocreatine-creatine system (8-10 sec)
• ATP
• Creatine phosphate
• The glycogen-lactic acid system (1.3-1.6 min)
• Glycolysis
• Stored glycogen split into glucose 2
  pyruvate E
• If insufficient O2, pyruvate converted to lactic
  acid
• The aerobic system (unlimited w/O2 nutri.)
• Oxidation of glucose, FA, aa E
• Occurs in the mitochrondria with sufficient O2