Transcript Document

Circulatory Physiology I: we don't have it yet
Circulatory Physiology II: Dynamics and Control of the Body Fluids
Circulatory Physiology III: Arterial Pressure and
Hypertension
First course
Randy Thomas (IBISC FRE 2873 CNRS/Univ. Evry)
http://saphir.physiome.fr/
SAPHIR:
"a Systems Approach for PHysiological Integration of Renal, cardiac, and respiratory functions"
oxygen
delivery
thirst
muscles
kidney
ADH
control
local blood
flow
control
autonomic
control
heart rate…
capillary
membrane
dynamics
circulatory
dynamics
angiotensin
control
aldosterone
control
tissue fluids,
pressures,
gel
pulmonary red cells,
dynamics viscosity heart
hypertrophy
electrolytes
& cell
water
Guyton, Coleman, Granger (1972) Ann. Rev. Physiol.
Guyton's modular Systems Model for blood pressure regulation
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SAPHIR (cont.)
Na, K, Cl,
glucose,
urea,
blood pH,
HCO3, CO2,
O2, Ca++,
Mg++,
mannitol,
blood
hemoglobin,
COP,
phosphate,
sulfate,
NH4+
Ikeda, N., et al., "A model of overall regulation of body fluids".
Annals of Biomedical Engineering, 1979. 7:135-166.
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Outline
Guyton's 'engineering' approach to BP regulation
•
Why regulate blood pressure?
•
What are the problems for BP control?
•
The hierarchy of pressure control systems.
•
Relevant principles of Control Theory
•
Quantitative evaluation of all aspects of BP
regulation: the Guyton model(s)
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1. Guyton's 'engineering' approach to BP regulation
Why does the body need to regulate blood pressure?
1. To ensure adequate blood flow to each organ
•
autoregulation of individual organs works best with a
steady pressure at input
•
SO - the Most important function of BP regulation is to
MAINTAIN A STEADY PRESSURE HEAD
2. (corollary of (1)): avoid interference/competition among
the organs for blood supply
•
e.g., in sympathectomized dogs, exercise leads to
dramatic fall of BP in the brain..
3. Adjust BP to bodily needs (sleep, exercise…)
4. Keep BP high enough to supply all organs (>80mmHg),
but low enough to avoid damage to the vascular system
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1. Guyton's 'engineering' approach to BP regulation
What are the problems for control?
1. Maintain an appropriate long-term baseline level of BP.
•
this role is assured almost entirely by the kidneys, which
control blood volume and extracellular fluid volume
2. Provide appropriate short-term changes in the circulatory
system in the face of the many acute stresses we
encounter
•
entirely independent of blood volume changes (too slow)
•
must ensure adequate perfusion of all organs, but esp. the
brain and the heart
•
depends on controlling strength of the heart, capacity of
blood vessels, and total peripheral resistance (TPR)
•
accomplished via nervous control and hormonal signals
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1. Guyton's 'engineering' approach to BP regulation
The hierarchy of pressure control systems.
1. The two major parameters of BP control: TPR and CO
Art. Press. = Cardiac Output X Total Peripheral Resistance + Right atrial pressure
-- but this simplistic approach is "useless"!
2. The body's approach: a hierarchy of short- and medium-term damping
and long-term control
• short-term (seconds to minutes)
• cardiovascular reflexes mediated by the nervous system
• intermediate-term (minutes to hours)
• capillary fluid shift from circulation to interstitial fluid
• delayed compliance of the vasculature
• hormonal controls (angiotensin, vasopressin,..)
• long-term (hours, days, weeks..)
• in response to numerous signals from elsewhere in the body, the
kidney manages overall fluid and solute balance, which determines the
baseline level of blood pressure … --> with INFINITE GAIN!
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1. Guyton's 'engineering' approach to BP regulation
The hierarchy of pressure control systems
from Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and
Hypertension. Philadelphia, W.B. Saunders.
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1. Guyton's 'engineering' approach to BP regulation
The hierarchy of pressure control systems.
from Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and
Hypertension. Philadelphia, W.B. Saunders.
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1. Guyton's 'engineering' approach to BP regulation
Relevant principles of Control Theory
Three types of control:
- proportional feedback
- integral feedback
- feed-forward control
Quantitative modeling, using
control systems diagrams:
Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure
and Hypertension. Philadelphia, W.B. Saunders.
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1. Guyton's 'engineering' approach to BP regulation
Relevant principles of Control Theory -2
Gain:
(max-final)/(final-normal)
Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and Hypertension. Philadelphia, W.B. Saunders.
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1. Guyton's 'engineering' approach to BP regulation
Relevant principles of Control Theory -2
Infinite Gain of the Kidney-blood volume feedback control system
Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and Hypertension. Philadelphia, W.B. Saunders.
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Modular systems-model of blood pressure: Kidney module
INPUTS
AUM: sympathetic
vasoconstrictor effect on
arteries
afferent,
efferent,
& total
resistan
ce
VIM: Blood viscosity
PA: aortic pressure
PPC: plasma COP
RBF: Renal Blood Flow
REK: percent of normal
renal function
CNE: third factor effect
AHM: ADH multiplier
AM: aldosterone multiplier
volume
reabsorption
glomerular
filtration
sodium
excretion
OUTPUTS
NOD: rate of renal Na+
excretion
VUD: rate of urine output
renal blood flow
CNE
AHM
AM
AUM
VIM
PPC
PA
RBF
REK
NOD
VUD
Guyton, A.C., T.G. Coleman, and H.J. Granger, "Circulation: Overall regulation."
Annual Reviews of Physiology, 1972. 34:13-44.
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The Infinite-Gain feature of the
kidney - blood volume - pressure regulator:
The (acute) renal function curve
from Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and
Hypertension. Philadelphia, W.B. Saunders.
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The Infinite-Gain feature of the
kidney - blood volume - pressure regulator:
The (acute) renal function curve and Net sodium intake
from Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and
Hypertension. Philadelphia, W.B. Saunders.
15
The Infinite-Gain feature of the
kidney - blood volume - pressure regulator:
The acute vs. chronic renal function curves
from Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and
Hypertension. Philadelphia, W.B. Saunders.
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The Infinite-Gain feature of the
kidney - blood volume - pressure regulator:
Shifting the Renal Function Curve…
from Guyton, A. C. (1980). Circulatory Physiology III. Arterial Pressure and
Hypertension. Philadelphia, W.B. Saunders.
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Several renal transporters implicated in health problems
ENaC
TSC
AQP2-3
ROMK1
NKCC2
CaSR
AQP1
UT-B
AQP1
UT-A2
ClC-Ka
AQP2-4
UT-A1,A3
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Distal Tubule JNa too high --> Hypertension
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http://saphir.ibisc.fr/
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