Introduction to human physiology

By:-Demeke A.
lecture outline
 Introduction

 Regulatory mechanisms in physiology ( homeostasis )

o feedback VS feed forward

 Body fluid compartments

 Measuring the volume of the body fluid

compartments

2
 Reference Books
1. G. Tortora and B. Derrickson 2007. Introduction
to the human body. The essentials of anatomy
and physiology. Seventh edition.
2. Guyton and Hall. Text book of Medical
physiology, 12th edition
3. Principles of human physiology
4. Kenneth S. Saladin. Anatomy and physiology. 3rd
edition.
5. Indu Khurana textbook of medical physiology 1st
edition.
6. Fredric H. Martini 1993. Fundamentals of
anatomy and physiology. 4th edition.
3
Objectives
At the end of this lesson the students will be able to:-

•Define physiology and explain historical development of

human physiology

•Define homeostasis and its historical reviews

•List and appreciate the types of homeostasis mechanisms.

•Compare feed back vs feed forward mechanisms

•Appreciate the body fluid composition

4
 Introduction

What is human physiology?

Greek;- - physis = "nature, origin";
o logia, ="study of“ . ology- branch of
learning
o biological sciences -deals with the study of
body functions, which are:
-Biochemical
– physical
-mechanical

5
 Introduction cont’d

is the study of how the human body functions.

-with emphasis on specific cause-and-effect mechanisms.

• is the study of biological function—of how the body works:-

-from cell to tissue, tissue to organ, organ to system

-and of how the organism as a whole accomplishes particular

tasks essential for life.
 It is also concerned with conditions which affect normal
functions of body parts

6
 History of Physiology

•
Aristotle 384 – 322 B.C) – coined the term physiology

• according to Aristotle , physiology meant the study of nature

• he was regarded as the father of natural history

Galen (130 -201 A.D.) - believed the working body was not
understandable without knowledge of its structure.
 Began modern experimental physiology.
Eg studying body parts of animals like blood vessels and their functions.

7
William Harvey (1578–1657)-blood pumped in a closed system of
vessels

8
• Physiology is the basis for

– pathophysiology: how physiological processes are

altered in disease or injury
– pharmacology

– immunology

– biochemistry

– microbiology

– medicine
9
 Physiology is the basis of medicine
It-
tries to correct dysfunction or minimize its effects
tries to restore system towards normal homeostatic
set point
Approaches to Physiology

mechanistic approach - asks “how” a function occurs

e.g. how do red blood cells carry oxygen?
teleological approach - asks “why” a function occurs
e.g. why do red blood cells carry oxygen?
physiology is a quantitative science:
almost all physiological parameters are measurable and expressed
quantitatively
oe.g.
blood pressure 120/80 mm Hg
blood glucose level 70-110 mg/dl
How can study of physiology help
you?
 understanding the “normal” function gives incite
into potential problems that can occur
 gives an idea of the potential cause or extent of
problems resulting from disease
 understanding the normal helps to search for
potential treatments
 Helps to understand how substances impact the
body –Eg. drugs

12
 Homeostasis and History of homeostasis

 What is homeostasis?

• What happens when homeostasis is disrupted?

• How is homeostasis maintained?

• What is feedback vs feed forwardf?

• What are the components of feedback loop?

• What are negative and positive feedback loops?

13
Homeostasis and History of homeostasis
•In Greek:
o homeo= same”
o stasis= standing still
•maintenance of nearly constant conditions in the internal
environment despite:
o changing conditions in the external environment and/or
the internal environment
•necessary for the well-being of individual cells and of the
entire body
•It is the body's attempt to maintain a constant internal
environment

14
• A process that maintains the internal environment of living
systems in a more or less constant state.
• Homeostatic control systems cannot maintain complete

constancy of any given feature of the internal environment.

• measured values are compared with a predetermined "set
point“.

15
 History of homeostasis

Claude Bernard (1813 – 1878) – internal environment remains constant

despite ever changing external environment

Claude Bernard, a French physiologist in the 19th C

 He stated that, ‘every cell in body is bathed with the fluid
environment called extra cellular fluid (ECF).
He called the ECF = internal environment of the body
ECF contains optimum amount of all the needed substances for
cells
16
 History of homeostasis cont’d

The concept of homeostasis was first articulated

by the French scientist Claude Bernard (1813-1878).

– Bernard observed that the milieu interieur (internal
environment) remains relatively constant despite:
o changing conditions in the external environment
and/or the internal environment itself

17
 History of homeostasis cont’d

• According to Claude Bernard

the internal environment is the extra cellular fluid(ECF, fluid out side
cells)
 ECF is considered external environment b/c all cells get their
supplies from it and dispose their wastes to the ECF
• Stated,“La fixite du milieu interieur est la condition de la vie
libre.
• The fixity of the internal environment is the necessary
condition for a free and independent life.”
• Regarded the plasma as the internal environment.

18
 History of homeostasis cont’d

• American Physiologist Walter Cannon (1871–1945)

 Coined the term “Homeostasis” to describe the internal
constancy.
 Explained the significance of ANS in homeostasis.

• He states; ‘maintenance of constant conditions in the ECF as

homeostasis.’
19
 Body is constantly facing a change in external environment
and activities that may alter the balance of important
variables.
o therefore, it is more accurate to say that the internal
environment is in a dynamic steady state
Note:
 Dynamic = parameters do change
 steady state= parameters change in very narrow limits
 Disease, by and large, is a failure of homeostasis
 excessive perturbations result ultimately in death of the
organism
20
 Contribution of each system in maintaining homeostasis
 essentially all organs and tissues of the body contribute to
homeostasis
 Nervous system
o regulates muscular activity and glandular secretion
o responsible for all activities associated with the mind
 Endocrine system:
o regulates metabolic processes through secretion of hormones
 CVS:
o transports required substances and removes waste products.
 Respiratory system:
o provides respiratory gases(o2)
o regulates acid-base balance (pH)

21
 GIT:
o digests food to provide nutrients to the body
 muscular system:
o body movement; maintain body balance,
thermoregulation and stabilize joints
 renal system:
o eliminates waste products from the body; regulates
blood volume and blood pressure; regulates acid-base
balance (pH).
 reproductive system:
• not essential for homeostasis
o not essential for survival of the individual
• for perpetuating the species 22
Components of homeostatic control system

1. Receptors( detectors)
 cells/tissues/protein molecules
 detects a change( stimulus) in the internal or external
environment from the set point
o sends sensory information to the control center through
afferent fibers
 set point = normal value

23
 Components cont’d
2. Control center
 compares the measured values(the deviation) with a
predetermined "set point“.
 It uses error signal(difference b/n measured value and the
set point) to determine response
 usually the control center is the brain
3.Effectors
 are muscles and glands
 receive commands from the control center
o produce response either by opposing or enhancing the
stimulus
24
25
 Homeostatic Control Mechanisms
Control
3 Input: center
4 Output:
Information Information sent
sent along along efferent
afferent pathway to
pathway to

Receptor (sensor) Effector

2 Change
detected
by receptor

Response of
5
effector feeds
back to influence
magnitude of
1 Stimulus: stimulus and
Produces I mb
al a returns
change nce variable to
in variable homeostasis
Variable (in homeostasis)
I mb
al a
nce
Homeostasis control system

27
Homeostatic control/regulation system
 Homeostasis is maintained by
two general categories of regulatory mechanisms:
1. Intrinsic regulation/auto-regulation
 results when cell, organ or system adjusts its activity
automatically
 independent of neural/endocrine control
characteristics ：
o amplitude of the regulation is smaller than extrinsic
o extension of the effects is smaller than extrinsic

28
2. Extrinsic regulation
o results from activity of nervous system or endocrine system
A. the nervous regulatory mechanism
 regulates homeostasis by releasing chemical messengers –
neurotransmitters
 response fast; acts exactly or locally, last for a short time
 composed of three major components
o sensory = detects a change
o integrative = formulate appropriate response
o motor = carry appropriate response to effectors

29
30
B. Hormonal/chemical regulation
 performed by hormone or active chemical substance in blood
or tissue
 it response slowly, acts extensively and lasts for a long time

31
 Homeostasis control systems
 there are two homeostatic control mechanisms
1. feed back mechanism
2. feed forward mechanism
A. Feedback control
• Changed in the controlled variable brings a corrective
response.
• The regulatory processes established after the change
developed
B. Feed forward control
• The regulatory processes established before the change
developed
• By expectation
32
 Homeostatic control mechanisms cont’d

1. Feed back mechanism

 response is given after a stimulus occurs
A. Negative Feedback
 output returns to the normal input, i.e. response is in the
opposite direction as the stimulus
 defends the set point
 reverses the initial deviation
 widely used by the body
 it favors stability

33
 Negative feed back cont’d
Examples of negative feedback (closed loop)
 temperature regulation
 regulation of PaCO2
 blood pressure regulation
 regulation of plasma volume
 regulation of acute hemorrhage
 regulation of hormonal secretion
 regulation of blood glucose

34
35
Fig. Regulation of body temperature 36
 Blood Pressure regulation cont…..d

37
The baroreceptor reflex: the response to increased blood pressure
38
39
40
fig: regulation of blood glucose level

41
 Gain
 Degree of effectiveness with which a control system maintains
constant condition.
The ability of the control system to restore the system to its set point is called gain.
Gain = Correction = amount of correction of abnormality
Error amount of abnormality still remaining

 the higher the gain of a system, the better the control system

Eg .Bp set point=100mmHg..decreased to 75 due to blood loss,if our

body restore Bp to 95mmHg. So correction =20mmHg and
remaining error=5mmHg hence gain=4mmHg

42
Fig: Gain of control system(in moderate hemorrhage)

43
 Feed back cont’d
B) positive Feedback
 output not returned to the normal input, i.e. response is in the
same direction as the stimulus
o amplifies the change
 vicious circle which may leads to death
 rare in biology and has less physiological advantages
 can leads to instability

 Original stimulus intensified and change facilitated for self

amplification
 Changes from normal value is made greater.

44
Examples of positive feedbacks
Uterine contraction during labor
LH surge at mid menstrual cycle
Blood clotting
Action potential
Severe shock
Viral infection: virus invades cellreplicates in
cellmany virusesinvasion of other cellsfurther
replication

45
 During child birth (labor):
 1. Uterine contraction is enhanced as the head of the baby stretches
the cervix.

46
2. LH surge:
LH cause release of estrogen, the estrogen released causes
release of more and more LH.

47
48
 3. Blood clotting:
 when a blood vessel is ruptured
oclotting proteins gets activated

activated clotting factors will activate the inactive clotting factors
othis process continues until clotting ceases bleeding

activation of one clotting factor results in activation of

many in a positive feedback cascade.

49
4. Generation and propagation of the action potential:
 Stimulated nerve fiber  leakage of Na+ channels  entry of few Na+
stimulates the opening of more and more Na+ channels so that influx
of more Na+

50
positive feedbac that can lead to progression
of shock

51
 Feedback has got three disadvantages
 compensation is generally incomplete
 responses may be slow
 too much feedback causes instability

52
 2.Feed forward
 disturbance is sensed and corrective measure is taken in anticipation
of a change
 mainly the result of learning (training)
 usually operates with negative feedback mechanisms
e.g. increase in insulin secretion during digestion before blood glucose
rises above the normal level
 increased heart rate and RR just before a race
 shivering before diving into the cold water
 digestive juice secretion before food inter into GIT by thought,
smell and seeing.

53
Significance of feed -forward :
•adaptive feedback control (makes the human body to
foresee and adapt the environment promptly and exactly)
•prepare the body for the change

54
The fluid environment of the body/body
fluid
 approximate composition of an average adult
human per body weight
water = 60%
proteins = 18%
fats = 15%
minerals = 7%

55
Body fluid functions
transportation
remove wastes
protection (CSF, amniotic fluid, and tear)
media for cellular metabolism
regulate body temperature
sample source for experiment/diagnosis

56
 Body cont’d
 makes up
 55%-60% of the total body weight in adult male and
 50%-55% of the total body weight in adult females
 75%-80% of their weight in infants(birth-1yr age)
• Total body water(L) = body weight (kg) ×
percentage of body wt that is fluid

57
PERCENTAGE OF H2O IN TISSUES
Body fluid composition of tissue varies by
 tissue type
o lean tissues have higher fluid content than fat
tissues(therefore overweight/obesity  body
fluid)
 gender
o males have more lean tissues and therefore
more body fluid
o females have more fat tissue = less water
 age
o lean tissue is lost with age and body fluid is lost
with it or caused by increased fat accumulation with
age
o Body water content reduced with age

59
 Body Fluid Compartments (ECF and ICF)
 Total body fluid is distributed mainly between two
compartments:
 the intracellular fluid (ICF)
 the extracellular fluid (ECF)
 Intracellular fluid (ICF): fluid inside cells
 contains 2/3rd of the total body fluid
 Extracellular fluid (ECF)
 all the fluids outside the cells are collectively called
the extracellular fluid
 Contains 1/3rd of the total body fluid

60
Extra-cellular Fluid (ECF)
 All the fluids outside the cells are collectively called the
extracellular fluid.
 Contains about 20% of body weight (14 L)
- Fluid in vascular system =25% of ECF-in the capillaries
- Fluid in interstitium =75% of ECF-fluid in spaces b/n
cells or tissue fluid
- Transcellualr fluid – fluid in some space or secretions

•  Lymph, CSF, ocular fluid, synovial fluid(in joints) ,

peritoneal, pericardial fluid , pleural fluid, and fluid in the

secretions such as in the Saliva, Digestive juice, Hormones

and Tear

61
 Intracellular fluid(ICF)

All fluid inside inside cells

• About 28 of the 42 liters of fluid in the body are
inside the 75 trillion cells
• are collectively called the intracellular fluid.

• Thus, the intracellular fluid constitutes about 40

per cent of the total body weight in an” average”
person (70kg).

62
body fluid regulation, including the major body fluid
compartments and the membranes that separate these
compartments

63
 Magnitude of body fluid volume in the d/t
compartments

64
• Two largest compartments of the extracellular fluid
are:
 interstitial fluid (fluid b/n cells), which
makes up more than 3/4th of the extracellular
fluid and
 plasma (liquid portion of blood), which
makes up 1/4th of the extracellular fluid
NB. there is another small compartment of fluid that is
referred to as transcellular fluid

65
 ECF cont’d
• Trans cellular fluid include:
o synovial fluid(found in joints)
o peritoneal fluid(in the peritoneal cavity)
o pericardial fluid( in the pericardial cavity)
o pleural fluid(in the pleural cavity)
o intraocular fluid(in the eyes) and
o cerebrospinal fluid( in the subarachnoid space)
o Secretions like saliva, gastric juice etc
 Trans cellular fluid is usually considered to be a
specialized type of extracellular fluid

66
67
 Constituents of ICF & ECF

 composition of the body fluids is not uniform

o ICF and ECF have different concentrations of
various solutes
o variation is due to deferential permeability of cell
membrane to different substances
 ICF= more K+,Mg2+, phosphate,sulphate, proteins
than ECF
 ECF= more Na+, Ca2+, Cl-, Hco3- than ICF
 Inside cells= more negative ions than ECF

68
Body fluids contain equal amounts of cat ions
and an ions
because positive charges = negative charges.
Cations:
Major ion in ECF=Na+
– Major ion in ICF=K+
– Na-K pump in cells of mammals to:
– Push out Na that leaks into cells
– Push in K that leaks out of cells
Anions: Large organic molecules within cell.
– . proteins with phosphates remaining inside
cell because they are too large to diffuse out.

69
Main ECF anions: Cl -, HCO3-
• Cl- is not exclusively outside cells; distributes
according to electrical forces.
• Many cellular an ions cannot diffuse out;
hence Cl- tends to stay mainly outside cells.

The Donnan Effect:This is a distribution

asymmetry of a diffusible ion (Cl-) due to the
presence of a non-diffusible ion (proteinate)
inside the cell.

70
Constituents of ICF and ECF fluids

71
72
Ionic composition of plasma and Interstitial
Fluid
 plasma and interstitial fluid are separated only by
highly permeable capillary membranes
higher concentration of protein in the plasma
 proteins cannot pass through the capillary
membrane
 plasma proteins
o has net negative charge
o tend to bind cations and repel anions  more
positive & less negative ions in the plasma than IF
Donnan effect

73
 Fluid intake and output
 to remain properly hydrated ‘water intake must equal
water output
Daily intake of water
 ingested in the form of liquid or water in the food
o 2100ml/day
 synthesized in the body(from metabolism)
o 200ml/day
o intake is highly variable :
 among different people
 depending on climate, habits, and level of
physical activity
Daily loss of body water
i. insensible water loss
o we are not consciously aware of it
oloss by diffusion through the skin= 350ml/day
oloss through the respiratory tract= 350ml/day
ii. sensible water loss
o we are consciously aware of the loss
oloss in sweat = 100ml/day( vary with activity and
temperature)
oloss in feces= 100ml/day
oloss by the kidneys(urine)= 1400ml/day
Daily intake and output of water (ml/day)
water is regulated in the body by
 GIT
 kidneys
 hypothalamic thirst center
 ADH secretion
 ADH increases water reabsorption from the kidneys to
the blood
 activation of the thirst center increases water intake
 the hypothalamic thirst center is stimulated:
 by a decline in plasma volume of 10%–15%
 by increases in plasma osmolality of 1–2%
 decreased blood pressure of 10%

77
78
concentration of body fluid
amount of solute in the body fluid can be measured
by mole or equivalent or osmole or mg
o body fluid conc. can be expressed as mole/L or
equi/L or osmoles/L
o 1mole= gram mwt of a substance e.g. gram mwt.
of glucose = 180gm
o equivalent = number of moles X valence
e.g. 1mole of ca2++= 1mole X2= 2 moles of ca2+
+
o osmole= number of mole X number of osmotically
active particle/molecule
e.g. 1mole of Nacl= 1mole X 2= 2osmole/l

79
 Osmolality and Osmolarity of body
fluids
Osmolality
 the total concentration of all particles that are free in
a solution expressed as osmoles per kilogram of
water(osmoles/Kg of H2o)

Osmolarity
total concentration of all particles that are free in a
solution expressed as osmoles per liter of water
particles bound to macromolecules do not contribute
at all to osmolality
 the unit is osmol 80
 osmolarity cont’d
• one osmol (1osmol) is 1gm molecular weight of
osmotically active particle if that molecule cannot
dissociate further
e.g 1gm mwt of glucose(180gm of glucose) is equal
to 1osmol of glucose per liter of solution

• if the substance can dissociate further to other

particles the total osmole will be equal to the
number of particles
e.g.
• 1gm mwt of NaCl(58.5gm) is equal to 2osmoles b/c
NaCl can dissociate in to two osmotically active
particles( Na+ and Cl-)
81
 osmolarity cont’d
 in biological conc. of solutes are usually quite low
– milliosmole (mOsm), is commonly used
 In all body fluid compartments, humans have an
osmolarity of about 285mosm/L – 300mosm/L
Note:
o About 80% of the total osmolarity of the interstitial
fluid and plasma is due to sodium and chloride ions
 50% of ECF osmolarity is contributed by Na+
o For ICF, almost half the osmolarity is due to
potassium ions .

82
plasma osmolarity
•plasma
– clinically accessible
– dominated by [Na+] and the associated
anions
– under normal conditions, ECF osmolarity
can be roughly estimated as:
– POSM = 2 [Na+]p

83
 Tonicity of a solution
 Tonicity is the effect of a solution on osmotic
movement of water
 Particles which can freely cross a membrane
do not affect tonicity
 Dictated by the particles that can't cross the
membrane (such as proteins)
 It can be iso, hypo or hyper tonicity

84
Isotonic solution (isotonicity)
 Have the same osmolar concentration of non-
penetrating solutes with that of the body fluid
o regardless of the conc. of membrane penetrating
solutes
if a human cell is placed in isotonic solution:
there will be no change in cell volume (cell will neither shrink nor
swell)
e.g.
0.9%normal saline (NS) or
5 % dextrose in 0.9% NS
ringer lactate (RL)

85
86
Hypotonic solution
Has less osmolar concentration of non permeant
solutes than that of the body fluids

- regardless of the concentration of membrane-

penetrating solutes present
If a human cell is placed in hypotonic solution water
will diffuse into the cell, causing it to swell

e.g. 0.45%Nacl solution(NS)

87
Hypertonic solution
Has greater osmolar concentration of non-penetrating
solutes than the body fluids

- regardless of the concentration of membrane-

penetrating solutes present
if a human cell is placed in a hypertonic solution

owater will flow out of the cell into the extracellular

fluid causing the cell to shrink

e.g. 1% Nacl

88
 Osmotic pressure of a solution

Pressure needed to prevent the movement of solvent

across a semi - permeable membrane
is pulling pressure that tends to pull water into the
solution
o Hydrostatic pressure of a solution is a “pushing
pressure” that tends to push water out of the
solution
Its magnitude is equal to the magnitude of the
opposing hydrostatic pressure necessary to completely
stop osmosis

89
 It is indirect measurement of the water and solute
concentrations of a solution
 The higher the osmotic pressure of a solution

– the lower the water concentration

– the higher the solute concentration

 is determined solely by the number of molecules in
that solution
 It is not dependent on such factors as the size of the
molecules, their mass, or their chemical nature (e.g.,
valence)
90
 Osmotic pressure (π), measured in
atmospheres (atm), is calculated by van't
Hoff's Law as

91
 To exert osmotic pressure across a membrane, a
molecule must not cross the membrane
e.g. RBC membrane is impermeable to sucrose but
permeable to urea
– consequently, sucrose is termed an effective
osmole, whereas urea is an ineffective osmole
– to take into account the effect of a molecule's
membrane permeability on osmotic pressure, it is
necessary to rewrite equation

where σ is the reflection coefficient or

osmotic coefficient . for urea osmotic
coefficient = 0 , sucrose has osmotic
coefficient= 1 92
93
A. Iso-osmotic solution
a solution having same of solute concentration with that
of body fluid
– regardless of its composition of membrane-
penetrating and non-penetrating solutes
– it can be isotonic or hypotonic solution

B. Hyper-osmotic
a solution containing greater solutes conc. than body fluid

– regardless of its composition of membrane-

penetrating and non-penetrating solutes
– it can be isotonic, hypertonic or hypotonic sol.
94
C. Hypo-osmotic
a solution containing less solutes conc. than body fluids

– regardless of its composition of membrane-

penetrating and nonpenetrating solutes
– is always hypotonic

95
Intravenous solutions
Measuring the volume of the body fluid compartments

 If a certain known quantity (Q) of some substance is injected into a

fluid compartment having a volume (V),
 then, when an equilibrium distribution of the substance is achieved,
the concentration of that substance in the container will be Q/V
 Concentration = Q/V ---------1
 Volume (V) = quantity of substance injected (Q)----2
concentration of substance(C)
 since we know Q and can determine the value of Q/V or
concentration, it is a simple matter to determine V ( the volume of
fluid compartment)

97
Criteria for selecting a substance to measure body fluid
volume
 be nontoxic

 be rapidly and evenly distribute throughout the

nominated compartment
 not be metabolized

 not be excreted (or excretion is able to be corrected

for) during the equilibration period
 be easy to measure

 not interfere with body fluid distribution

98
 Measurement of body fluid volume
Volume Indicators (markers)
Total body 3
H2O, 2
H2O, antipyrin
water
ECF 22
Na,125I-iothalamate, thiosulfate,
inulin
Plasma 125
I-albumin, Evans blue dye (T-1824)
volume
ICF Total body water – ECF
Blood volume Cr-labeled RBC or
51
= plasma
volume
(1-
Hematocrit)
IF Extracellular fluid volume – Plasma
volume 99
Indicators used for measuring plasma volume,
ECF volume and total body H2O
Compartmen Criterion Indicators
t
1. Plasma Substance 1. Evans blue dye;
should not 2. radioiodinated
cross fibrinogen;
capillaries 3. radioiodinated albumin
1. ECF Substance Isotonic solutions of
volume should cross sucrose, inulin, mannitol,
capillaries but NaCl
not cross cell
membranes
1. Total Substance Heavy H2O, tritiated H2O,
body H2O distributes aminopyrine, antipyrine
(TBW) evenly in ICF
& ECF
A. Plasma volume measurement
 simple to measure

 the substance used should not cross capillary

wall after IV injection

e.g. - radioiodinated albumin(I-albumin)

- Evans blue dye

- radioiodinated fibrinogen

101
How indicator dilution technique is used to measure blood volume.
Known quantity of tracer is administered (A), time is allowed for complete
102
mixing
Plasma volume
Example.
 an amount of 131I-albumin having 350,000 counts per
minute (cpm) is injected intravenously
 one hour later, 10 mL sample of whole blood are
withdrawn and centrifuged
 this whole blood sample consisted of 5.5 mL of
plasma and 4.5 mL of packed blood cells
 then, 1 mL of the plasma is analyzed and found to
contain 100 cpm
 thus, plasma volume (PV) = Q injected
concentration
 in this case, therefore, PV = 350, 000cpm = 3.5L

100 cpm/mL 103

 Total blood volume

 Given these data, one can also determine the total

blood volume employing a measure known as the
hematocrit, which is defined as the fraction of the total
blood volume comprised of cells, mainly red blood
cells.
 in this case, the hematocrit (Hct) is:
 Hct = 4.5ml/ 10ml = 0.45 = 45%
 the total blood volume (TBV) is given by:
TBV = PV__
1 - Hct
 in this case, therefore,
TBV = 3.5L = 3.5L = 6.4L
(1 - 0.45) 0.55
104
Extracellular fluid volume
 a substance is used can readily move out of capillary
walls but not enter to cell membranes
e.g. polyfructoside, inulin, mannitol

Inulin
- minor complication( pass capillary membrane &
filtered to urine & excreted)

105
 Take into account the amount of the substance lost from the body in
the course of the measurement
ECF = Q injected – Q lost in urine
concentration

Example: An individual’s urinary bladder is catheterized

and drained, then 2.4 g of inulin is injected
intravenously; 6 hours later, a venous sample is
withdrawn and found to have a plasma inulin
concentration of 0.1 mg/mL.
During those 6 hours, 200 mL of urine was produced
having an inulin concentration of 5 mg/ mL.
Thus, 1.0 g of the original 2.4 g of inulin injected was
lost.

ECF volume = 2.4 g – 1.0 g = 2400mg – 1000mg =

106
14000mL =14L
 Total Body Water
 Substance distributes evenly in ICF & ECF

e.g. antipyrine, deuterated water (2H2O) or tritiated

water (3H2O))

 Disadvantage:

o substances are lost from the body via every route

open for the loss of water
but only 2 hours are needed for them to achieve a
uniform distribution in the TBW and, during that
period, the amount of water lost by the body is less
than 1% of the TBW 107
Interstitial and Intracellular fluid compartments

 Volume of ISF and ICF compartments cannot be

measured directly.
o VISF = VECF - PV
o VICF = TBW -VECF
key:
 VISF= volume of interstitial fluid
 VICF= volume of intra cellular fluid
 VECF= volume of extracellular fluid
 PV= plasma volume
 TBW = total body water

108
Disruption of water balance
1. Dehydration
 is loss of fluid from the body
 reduction of ECF
 Water loss exceeding water intake
causes include:
o hemorrhage,
o severe burns,
o prolonged vomiting or diarrhea,
o profuse sweating,
o water deprivation, and diuretic abuse
Signs and symptoms:
 dry mouth, thirst, dry flushed skin, and oliguria,
hypovolemic shock
 Prolonged dehydration may lead to weight loss, fever,
109
and mental confusion.
Types of dehydration
A. Isotonic dehydration
loss of equal proportion of fluid and electrolytes
causes can be:
odiarrhea
ovomiting
oloss of isotonic urine
ohemorrhage
oburn
mechanism
loss of fluid from plasma loss from interstitium

110
Changes:
plasma volume= reduced
no change in ECF & ICF osmolarity

B. Hypertonic dehydration
more water is lost than electrolytes
obody fluid become hypertonic
Causes
owatery diarrhea
ofever, excessive sweating
odiabetes insipidus, diabetes
mellitus,alcoholism

111
Changes:
plasma volume = reduced
loss of fluid from the cell = reduced cell volume(cell
shrink)
increased ICF & ECF osmolarity

112
C. Hypotonic dehydration
 loss of more electrolytes than water

 causes can be

o Addison's disease = adrenocortical insufficiency

o reduction of aldosterone or

o increase ANP

changes:
 plasma volume = reduced

 fluid moves in to the cell= cells swell

 ICF & ECF osmolarity = reduced

113
Over hydration
A. Isosmotic overhydration

causes

a) oral/IV administration of large volume of isotonic

normal saline (0.9 % NaCl)

changes
 ECF volume ↑
 no change in osmolality of ECF/ ICF
 no change in cell volume

114
B. Hyperosmotic overhydration
causes
 oral/IV administration of large volume of hypertonic
saline
changes
 plasma osmolarity increases
 shift of fluid from ICF to ECF
o ICF volume decreases but ICF osmolarity
increases
o plasma volume increases
C. Hypo-osmotic overhydration
Intake of water exceeds the excretory capacity of
kidney

causes
o ingestion of large volume of water

oretention of H2O by kidney (SIADH)

Syndrome of inappropriate secretion of ADH

(ADH – anti diuretic hormone)

Over hydration
puffy eyelids

oedema

weight gain

117
3. Edema
 excessive fluid accumulation in the interstitial space

– tissue swelling
 caused by anything that increases flow of fluids out
of the blood stream or hinders their return
o increased capillary hydrostatic pressure

o decreased plasma colloid osmotic pressure

o increased capillary permeability

118
 Mechanisms of edema formation

CAUSE EXAMPLE

Pc Increased capillary pressure

(failure of venous pumps, heart
failure)
πc Decreased plasma protein osmotic
pressure
(severe liver failure, nephrotic
syndrome)
πi Increased capillary protein
permeability
(due to release of vasoactive
Impaired substances)
parasitic infection of lymph nodes
Lymphatic (e.g. burns, trauma, infection)
drainage (filariasis) 119
Causes
1. A reduced concentration of plasma proteins
(hypoproteinemia)
-decreases plasma-colloid osmotic pressure
 hypoproteinemia may due to:
- malnutrition(PEM)
- protein loosing enteropathy (malabsorption of
proteins
- protein loosing nephropathy(kidney diseases)
- liver disease(liver cirrhosis)

120
2. Increased permeability of the capillary walls

- due to tissue injury, allergic rxn(inflammation)

3. Increased capillary hydrostatic pressure

4. increased venous pressure

possible causes of increases venous pressure

- increased venous pressure as in pregnancy, venous

blockage (venous thrombosis)

- heart failure

121
5. Lymphatic blockage
- by filarial worm, tumour, after surgery etc
lymphatic obstruction in the extremities leads to
elephantiasis
elephant-like appearance of the swollen extremities

Elephantiasis 122
• Cutaneous edema is
referred to as "pitting"
when, after pressure is
applied to a small area, the
indentation persists after
the release of the pressure.
• Peripheral pitting edema, is
the more common type,
resulting from water
retention
123
124
Cellular non-pitting oedema - may be caused by:
A. Depression of cellular metabolism → ↓Na+-K+ pump →
Na+ influx into cell → Water following Na+ → Cellular
oedema

B. Inflammation→↑membrane permeability to sodium and

other ions that diffuse into cell with water → oedema

• Myxedema

125