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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/. thirst. oxygen delivery.

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randy thomas ibisc fre 2873 cnrs univ evry

Circulatory Physiology I: we don't have it yet Circulatory Physiology II: Dynamics and Control of the Body FluidsCirculatory Physiology III: Arterial Pressure and HypertensionFirst 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

thirst

oxygen

delivery

muscles

kidney

ADH

control

local blood

flow

control

angiotensin

control

capillary

membrane

dynamics

circulatory

dynamics

aldosterone

control

autonomic

control

tissue fluids, pressures, gel

electrolytes

& cell

water

pulmonary

dynamics

red cells,

viscosity

heart

hypertrophy

heart rate…

SAPHIR:"a Systems Approach for PHysiological Integration of Renal, cardiac, and respiratory functions"

Guyton, Coleman, Granger (1972) Ann. Rev. Physiol.

Guyton's modular Systems Model for blood pressure regulation

saphir cont
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.

outline
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)
1 guyton s engineering approach to bp regulation why does the body need to regulate blood pressure
1. Guyton's 'engineering' approach to BP regulationWhy does the body need to regulate blood pressure?
  • 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
  • (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..
  • Adjust BP to bodily needs (sleep, exercise…)
  • Keep BP high enough to supply all organs (>80mmHg), but low enough to avoid damage to the vascular system
1 guyton s engineering approach to bp regulation what are the problems for control
1. Guyton's 'engineering' approach to BP regulation What are the problems for control?
  • 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
  • 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
1 guyton s engineering approach to bp regulation the hierarchy of pressure control systems
1. Guyton's 'engineering' approach to BP regulation The hierarchy of pressure control systems.
  • 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"!

  • 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!
1 guyton s engineering approach to bp regulation the hierarchy of pressure control systems8
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.

1 guyton s engineering approach to bp regulation the hierarchy of pressure control systems9
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.

1 guyton s engineering approach to bp regulation relevant principles of control theory
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.

1 guyton s engineering approach to bp regulation relevant principles of control theory 2
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.

1 guyton s engineering approach to bp regulation relevant principles of control theory 212
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.

modular systems model of blood pressure kidney module

afferent, efferent, & total resistance

renal blood flow

volume reabsorption

glomerular filtration

sodium excretion

Modular systems-model of blood pressure: Kidney module

INPUTS

AUM: sympathetic vasoconstrictor effect on arteries

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

OUTPUTS

NOD: rate of renal Na+ excretion

VUD: rate of urine output

CNE

AHM

AUM

AM

VIM

PPC

REK

RBF

NOD

PA

VUD

Guyton, A.C., T.G. Coleman, and H.J. Granger, "Circulation: Overall regulation."

Annual Reviews of Physiology, 1972. 34:13-44.

slide14
The Infinite-Gain feature of thekidney - 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.

slide15

The Infinite-Gain feature of thekidney - 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.

slide16
The Infinite-Gain feature of thekidney - 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.

slide17
The Infinite-Gain feature of thekidney - 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.

slide18

Several renal transporters implicated in health problems

ENaC

TSC

AQP2-3

ROMK1

NKCC2

CaSR

AQP1

UT-B

ClC-Ka

AQP1

UT-A2

AQP2-4

UT-A1,A3