What is physiology?
Anatomy, physiology, …
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Anatomy is the science of the structure
Physiology is the science of the function
Anatomy and physiology are closely linked, in
particular physiology cannot be understood
without anatomy
In many respects, both are ‘closed sciences’
Anatomy
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Gross anatomy was reasonably well known
already in antiquity
Flourished in the west starting in the 12-13
centuries
Greatest period between the 16th and the 19th
centuries
Andreas Vesalius (1514-1564)
Andreas Vesalius (1514-1564)
Anatomy in the arts
Rembrandt van Rijn (1606-1669)
The anatomy lesson of Professor Nicolaes Tulp (1632)
Vesalius’s
Anatomy?
Anatomy today
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Anatomy goes into the microscopic
Tight links with molecular biology
Example:
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Neuroanatomy – anatomy of the nervous system
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Gross anatomy of the nervous system known
Fine structure is still worked out
Fine structure is dynamic: plasticity and learning
The use of molecular markers to study structure
Linked with physiology: structure/function
relationships
Neuroanatomy, 1800
Neuroanatomy, 1900
Pyramidal neurons and
interneurons ,precentral gyrus,
using Golgi staining
Santiago Ramon y Cajal, 1900
Neuroanatomy, 2004
Interneurons in rat primary
somatosensory cortex
Red: stained for calbindin
Green: stained for VIP
Staiger et al., J. Comp Neurol
468:179:189, 2004
Physiology
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Developed much more slowly than anatomy
Some general principles were known in
antiquity
Example: balance of the internal milieu
(‘homeostasis’ – we’ll see about that later…)
Four humors
Physiology
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Some important moments (I emphasize the
cardiovascular system because we will study
it in details!):
17th century: William Harvey first describes
the closed circulation
Before Harvey:
Some venous blood
enters the right
ventricle of the heart
Air enters the lungs and
flows into the heart
Arterial blood reaching
the brain is
transformed into
animal spirit, flowing in
the nerves
Arterial blood
supplies vital spirit to
the body, allowing it
to move
It is distributed to the
whole body by the veins
Venous blood is
generated in the liver,
receiving nutrients from
the stomach and
intestines
Some blood crosses over
into the left ventricle,
mixing up with air to
generate arterial blood
Before Harvey:
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Veins and arteries are separate, venous
blood and arterial blood are different
Two open systems: blood is constantly
generated (in the liver) or transformed (in the
left ventricle) and flows into the body
Venous and arterial systems connected to
some extent, mostly through micropores in
the septum separating the right and left
ventricles of the heart
After Harvey
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A closed system
Arteries supply blood from
the heart to the tissues,
veins collect blood from the
tissues to the heart
Arteries and veins
connected in the tissue
(through capillaries)
Right and left ventricles
connected through the
pulmonary circulation
Left
ventricle
Right
ventricle
Physiology
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Some important moments:
17th century: William Harvey first describes the
closed circulation
19th century: Claude Bernard formulates the modern
version of homeostasis – the constancy of the
internal milieu
Homeostasis
The parable of the poor unicellular
organism
Physiology
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Some important moments:
17th century: William Harvey first describes the
closed circulation
19th century: Claude Bernard formulates the modern
version of homeostasis – the constancy of the
internal milieu
19th century: Johannes Muller formulates the ‘law of
specific nerve energy’
Physiology
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Some important moments:
17th century: William Harvey first describes the
closed circulation
19th century: Claude Bernard formulates the modern
version of homeostasis – the constancy of the
internal milieu
19th century: Johannes Muller formulates the ‘law of
specific nerve energy’
In general, a slow development of our modern view
of the function of the body
Systems physiology:
Missing from the scheme:
Structure and motion:
 Skeletal system
 Muscles
Integratory systems:
 Nervous system
 Hormones
Physiology today
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Neurophysiology is the major field of systems
physiology that is alive and well
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Interdisciplinary interactions with medicine,
psychology, physics, philosophy…
Emphasis on information processing in neural
systems
Other systems are studied more and more
from a molecular perspective
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Control of blood pressure
Hormones and obesity
Principles of physiology
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Physiology is not a science in the sense of
the physical sciences – there are no ‘laws of
nature’ in physiology
Through observation and study of many
organisms that share both commonalities and
differences, it is possible to formulate
principles of physiology
Principles of physiology are more guidelines
than laws
Principles of physiology
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Structure/function relationships – interaction
with anatomy
Importance of basic physical laws
Homeostasis
Evolution: commonalities in diversity
Structure/function relationships
Physical laws
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Conservation laws
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Energy: example – relationships between lung
surface and oxygen consumption
Surface area of the lung and oxygen
consumption
Physical laws
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Conservation laws
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Energy: example – relationships between lung
surface and body mass
Mass: example – Harvey’s argument for the
circulation of blood
Harvey’s argument for the circulation of
the blood
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The heart refills and empties constantly
At each beat, the heart sends some amount of blood,
let’s say 10 ml (the correct number is more like 70 ml) to
the body
In half an hour, the heart beats a lot (about 2000 times)
So during half an hour, 20 litters of blood will flow
through the heart
This amount of blood is more than the amount of blood
in the whole body (about 5l), and cannot be generated
from what we eat or drink – it’s too much!
So: the blood that goes through the heart came in as
blood and goes out as blood – the vascular system is
closed
After Harvey
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Harvey had to assume that the
blood is transferred from one
ventricle to the other through
‘pores’ in the body and in the
lungs (later identified as the
capillaries)
This was an unverified
assumption, same as the
transfer of blood through the
heart septum in the old model
But overall, this theory fitted
basic physical laws better and
therefore was accepted
Physical laws
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Conservation laws
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Energy: example – relationships between lung
surface and body mass
Mass: example – Harvey’s argument for the
circulation of blood
Derived laws:
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Diffusion
Electrochemistry
…
Homeostasis
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The most important general principle of
physiology
The goal of all systems is to keep the internal
milieu constant
The internal milieu:
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pH, concentration of oxygen, level of glucose,
levels of metabolic waste products, core
temperature, …
Homeostasis and control
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Homeostasis is achieved through the use of
control systems
Control is usually achieved by feedback
Control systems are present at all levels,
from the organism down to the biochemical
pathways
‫מה זאת מערכת בקרה?‬
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‫שריר היא מערכת המסוגלת לבצע עבודה‬
‫כדי שהשריר יבצע עבודה‪ ,‬צריך להגיד לו מה לעשות‬
‫מערכת בקרה על השריר תתרגם את ההוראה‬
‫למונחים שהשריר מבין‪ ,‬ותפקח על הביצוע‬
‫מערכת בקרה בחוג פתוח‬
‫‪‬‬
‫‪‬‬
‫אם אני תמיד יודע בדיוק מה צריך לעשות‪ ,‬וגם אני‬
‫יודע בדיוק איך השריר מתנהג‪ ,‬אני יכול לחשב בדיוק‬
‫את קצב הירי של המוטונוירונים הדרוש לביצוע‬
‫המשימה‬
‫זו מערכת בקרה בחוג פתוח‬
‫משימה‬
‫חישוב קצב ירי‬
‫הפעלת השריר‬
‫יתרונות של מערכת בקרה בחוג פתוח‬
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‫ארכיטקטורה פשוטה‬
‫שגר ושכח‬
‫יציבות )לקלט קבוע יהיה פלט קבוע(‬
‫דוגמא‪ :‬שרירים של גלגל העין‬
‫חסרונות של מערכת בקרה בחוג פתוח‬
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‫ומה אם אנחנו לא יודעים בדיוק מה צריך לעשות‪ ,‬ומה‬
‫מצב השריר?‬
‫ומה אם אנחנו יודעים בדיוק מה צריך לעשות‪ ,‬אבל‬
‫העולם משתנה סביבנו?‬
‫דוגמא‪:‬‬
‫מערכות בקרה בחוג סגור‬
‫‪‬‬
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‫כדי לפתור את הבעיה הזאת‪ ,‬אנחנו עוברים לעבוד‬
‫בחוג סגור‬
‫מוסיפים למערכת רכיב שיכול למדוד את ביצוע‬
‫הפקודה‪ ,‬ולשנות את תפקוד המערכת בהתאם‬
‫משימה‬
‫בדיקת מצב‬
‫חישוב קצב ירי‬
‫הפעלת השריר‬
The muscle spindle reflex
Ia axon
(sensory)
Sensory
neuron
Motoneuron
Motor
axon
‫דוגמא‪ :‬בקרה על אורך שריר‬
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‫אורך השריר נקבע לפי קצב הירי של המוטונוירונים‬
‫קצב הירי של המוטונוירונים מושפע בחזרה מאורך‬
‫השריר‪ ,‬דרך רפלקס כישור השריר וסיבי ‪Ia‬‬
The muscle spindle reflex
Ia axon
(sensory)
Sensory
neuron
Motoneuron
Motor
axon
‫חסרונות של מערכת בקרה בחוג סגור‬
‫‪‬‬
‫ארכיטקטורה מסובכת‬
‫‪‬‬
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‫השריר מתקצר‪ ,‬יש פחות פעילות של סיבי ‪ ,Ia‬יש פחות‬
‫פעילות של מוטונוירונים‪ ,‬השריר מתארך‪ ,‬יש יותר פעילות‬
‫של סיבי ‪ ,Ia‬יש יותר פעילות של מוטונוירונים‪ ,‬השריר‬
‫מתקצר‪....‬‬
‫האם אפשר לצאת מהמעגל הזה?‬
Evolution
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The goal of homeostasis can be achieved in
multiple ways
Organisms share commonalities and
differences
Many of those can be accounted for by
evolutionary principles
Evolution
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Example: cardiovascular system
Transport of materials and heat in the body
by a circulating liquid
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Blood in a closed system (vertebrates)
Hemolymph in an open system (many
invertebrates)
Cardiovascular systems
Giant earthworm, Glossoscolex giganteus
Cardiovascular systems
Bivalve molusks
Cardiovascular
systems
Mammalian
Cardiovascular systems
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Why four chambers (some vertebrates have 3)?
Why separate pulmonary and systemic circulations
(some vertebrates have one)?
Why a closed system (some very large invertebrate
have an open system)?
To some of these questions, an answer can be
given in terms of physical limitations, energy
efficiency, and so on.
To other questions, the answer is ‘because an
animal evolved from an ancestor who already was
that way’
Evolution
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Example: kidney
In humans, one of the major roles of the
kidney is to regulate sodium levels in the
body
This is achieved by a dual process, in which
sodium is first filtered into the kidney, and
part of it is reabsorbed
Sodium balance and the kidney
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In the human kidney, 25,000 millimoles of
sodium are filtered into the kidney every day
About 25 millimoles of sodium are actually
excreted in the urine
More than 99% of the filtered sodium is
reabsorbed
An enormous metabolic load – about 10% of
the basal rate (as large as the brain!)
Why?
Summary: what will happen in the course?
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Modern view of classical physiology:
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The homeostatic systems:
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Integrative view of the control of the internal milieu:
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Heart and vascular system
Respiration
Kidney
Qualitative analysis of control systems
Fluid balance and blood pressure
pH
Modern physiology:
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Somatosensory system as a model system