The “Milieu Interieur”

• 1813-1878• Father of Physiology

The “milieu interieur” The “sea within us”

“The living body, though it has need of the surrounding environment, is nevertheless relatively independent of it. This independence which the organism has of its external environment, derives from the fact that in the living being, the tissues are in fact withdrawn from direct external influences and are protected by a veritable internal environment which is constituted, in particular, by the fluids circulating in the body Claude Bernard

Leçons sur les Phénomènes de la Vie Communs aux Animaux et aux Végétaux (1878)

Fig. 1-CO, p. xxviiiSherwood, Human Physiology

Fig. 1-6, p. 10

Fig. 1-7, pp. 12-13

~450 MYA

Body Fluid Compartments

Extracellular Intracellular

Na+ (mM) 140

15

K+ (mM) 4 120

Cl- (mM) 110 20

HCO3- (mM) 24 15

Ca2+ (mM) 1 10-7

pH 7.4 7.2

Osmolarity (mOsm/l) 300

300

Composition of Body Fluids

Similar values are found in fresh and salt-water fish, amphibia, reptiles, birds and other mammals.

Body Fluid Compartments

Plasma

3L or 5% Interstitial

12 L or 15% Intracellular

25 L or 40% Total

40 L or 60% BW

Flow

POsm

Feedback Loops – The Key to Homeostasis

positivenegativefeedforward

Non-physiologic positive feedback

Physiologic positive feedback

In mammals:

Remedies for disruptions of homeostasis

Induce/activate ion channels

Proton transport

Induce catalases, SODs

Water transport, solute synthesis

DNA damage responses

Induction of the heat shock response

Changes in extracellular ion concentrations:

Changes in extracellular pH:

Presence of oxidative stresses:

Changes in osmolarity:

Exposure to UV/Radiation:

Changes in temperature:

Glucose Homeostasis

The Cardio and Vascular Systems

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Besides muscles, there is an extensive conduction pathway in the heart. These are modified cardiomyocytes, not nerve cells

Action Potential in non-cardiac cell (a neuron)

Depolarization:Na+ rushing INTO cell

Repolarization:K+ rushing OUT of cell

Cardiac Muscle Cell action potential

AP in pacemaker cells

Arterial Side:10% blood volumehigh resistance vesselscontrols blood pressure

Venous Side:70% blood volumelow resistance, low pressure

Flow arterial side=Flow venous side

VASCULAR SYSTEM

Cardiac Output = the amount of blood pumped from 1 ventriclein 1 minute

In a healthy female it is about 5 L/min, in a male about 6 L/min

How would you calculate cardiac output?

CO = SV x HR

It is probably the most important index in cardiac medicine and is impaired in myocardial infarction, hypertension, valvular heart disease, congenital heart disease, cardiomyopathy, pulmonary disease, arrhythmias, drug effects, fluid overload, decreased fluid volume, and electrolyte imbalance.

(SV= stroke volume, the amount of blood (mls) ejected from the left ventricle per beat)

HR = heart rate in beats/min)

How local flow is alteredin exercise

Homeostasis: Exercise – an increase in demand for O2 and glucose

Orthostatic Hypotension:

Baroreceptor reflex

Homeostasis: Severe bleeding

Essentially a nervous system response

Essentially endocrine responses:

RAAS – renin angiotensin activating system(kidney)

Catecholamine release – adrenal medullaVasopressin release - pituitary

Multiple organ system response to homeostatic insult toblood pressure.

While clotting system, immune cells, platelets, liver proteinsact to eliminate immediate cause of insult