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Body fluid compartments

W
ater forms about 2/3 body weight (about 60%) or 42 Liters in adult males. The
remaining (40%) are:
➢ 18% proteins.
➢ 15% fat
➢ 7% minerals.

Factors affecting body water content:


1- Age: Water in newly born infants represent 80% of total body weight but in
old age, water represents only about 45%.
2- Sex: In females water represent 50% only of total body weight due to high
fat content.
3- Body mass index (BMI): in obese persons water represent 50% only of total
body weight.

Total body water is either:


➢ Intracellular fluid (ICF): inside the body & represent 2/3 of total body
water or 40% of total body weight or 28 Liters.
➢ Extracellular fluid (ECF): outside the cell & represent 1/3 of total body
water or 20 % of total body weight or 14 Liters).
✓ Intravascular: inside blood vessels (plasma) (1/4 of ECF or 5% of total
body weight or 3 L).
✓ Interstitial: bathing the body cells and
called internal environment (3/4 of ECF
or 15% of total body weight or 10.5 L).
✓ Transcellular fluid: small compartment
(about 0.5 Liter). It includes fluid in the
synovial, peritoneal, pericardial, and
intraocular spaces, as well as the
cerebrospinal fluid; it is usually
considered to be a specialized type of
ECF, although in some cases its
composition may differ markedly from
ECF.
ICF & ECF are separated by the cell membranes which keeps the composition of
the 2 fluids different.
The intravascular and interstitial fluids are separated by the capillary wall which is
highly permeable and allow for exchange between the two compartments but, it
keeps the protein content of intravascular fluid is more than that in interstitial fluid
due to the large size of proteins that cannot pass through the pores of the capillary
membrane.

T
he ECF contains large amounts of sodium (Na+) & Ca2+ with small
amounts of K+ as cations & Cl- & HCO3- as anions in comparison with the
ICF..
The ICF contains large amounts of potassium (K+) with small amounts of Na+,
Mg2+ as cations but phosphates, sulphates and proteins as anions.

The cells take up nutrients as glucose, amino acids & fats from interstitial fluid and
give out CO2 and other waste products to be excreted by the kidneys, lungs or skin.
Determination of water volume in different body
compartments
According to indicator dilution method or Fick's principle
Mass = volume X concentration
Measuring the intravascular volume:
If a known amount of indicator substance is injected in the blood it will be diluted
with the plasma only if its molecules can't cross the capillary wall and by measuring
the degree of dilution, the plasma volume can be calculated.
The substances used are for measuring plasma volume:
➢ Evan՚s blue dye.
➢ Radioactive iodine bound to albumin 131I or 132I.
➢ Radiolabeled fibrinogen or radiolabeled albumin.
The substances used are for measuring RBCs volume:
➢ RBCs containing radioactive chromium 51Cr, phosphorus 32P or iron
55
Fe.

Blood volume = plasma volume + RBCs volume.

Or after measuring the haematocrite value (HV)


𝟏𝟎𝟎
Blood volume = plasma volume ×
𝟏𝟎𝟎−𝑯𝑽

Measuring the ECF volume:


If the substance used can cross the capillary wall but can't cross the cell
membrane it will be diluted with all ECF as:
➢ Saccharides: as inulin, sucrose or mannitol.
➢ Ions: as Na thiocyanate, thiosulphate or radioactive sodium.

Measuring the total body water volume:


If it can cross both the capillary wall and cell membrane it will be diluted by the
total body water as deuterium oxide (D2O) or heavy water (deuterium is hydrogen
isotope) or the antipyrine (rarely used).
The greater the fluid volume the less will be the concentration after dilution.
The body fluid volume compartment that holds the substance is called the
distribution volume.
Initial volume (V1) X Initial concentration of substance (C1) = body fluid volume
compartment (V2) X final concentration of the substance after dilution (C2)
𝐕𝟏 𝐗 𝐂𝟏
V2 =
𝐂𝟐
Characters of the substance used:
Inert – non toxic – not utilized by tissues – not rapidly excreted – distributed
uniformly in the compartment to be measured.

Some body fluid compartments can't be measured directly by dilution method so it


is calculated by extraction. These are:
ICF volume = total body water – ECF volume
Interstitial fluid volume = ECF volume – intravascular fluid volume

Tissue fluid (interstitial fluid)


Definition: it is the medium in which the cells are bathed.

Functions: it is the medium for exchange of various substances between cells and
capillaries (O2 and nutrients diffuse from arterial end of the capillaries to reach the
tissue fluid then to the cells while CO2 and waste products from cells reach the tissue
fluid then diffuse through the venous end of the capillaries).
Formation of tissue fluid:
Through:
1- Filtration at the arterial end of the capillary.
2- Reabsorption at the venous end of the capillary.
Arterial end Venous end
Filtration force
(capillary hydrostatic 35 mmHg 17 mmHg
pressure)
Reabsorbing force
(plasma colloidal
osmotic pressure or 25 mmHg 25 mmHg
oncotic pressure) of
plasma proteins
NET pressure +10 -8
Net result Filtration Reabsorption
The fluid filtered from the arterial end of the capillaries is drained by mainly
by the veins but some of this fluid is drained by lymphatics.

Oedema
Definition: presence of excess fluid in interstitial space.

Causes:
1- Increased capillary hydrostatic pressure:
This increases the filtration of fluid from blood to tissue spaces. This may occur as
a result of :
a) venous obstruction by thrombosis
b) compression on the veins from outside by the uterus during preganacy
c) right sided heart failure.
2- Decreased colloidal osmotic pressure of the plasma as in
Hypoprotienaemia:
Causes:
1- Decrease synthesis of plasma proteins in Liver cell failure or
Undernutrition.
2- Increase loss of plasma protiens as in Severe kidney disease.
3- Increased capillary permeability due to Bacterial & chemical
toxins or Allergic conditions.
4- Lymphatic obstruction: (non-pitting oedema)
The accumulated fluid has a relatively high protein concentration. Lymphatic
obstruction occurs in: filariasis (elephantiasis) or Cancer invasion.
Nerve

• The function of nerves is to carry messages to & from central nervous system.
• The unit of structure of the nervous system is neuron which is specialized for rapid
transfer & integration of information.
❖ Neuron:
It is formed of cell body & cell processes
▪The cell body (Soma):
-It is surrounded with cell membrane. It contains cytoplasm & nucleus.
-Cytoplasm contains mitochondria, Golgi apparatus, endoplasmic reticulum,
pigment, fat, glycogen, neurofibrils & Nissil granules which are rich in ribose
nucleic acid (RNA) and play an important role in metabolism of cell.
▪ The processes:
The dendrites: short branches which receive the ingoing impulses.
The axon or nerve fiber which is a long process of the cell & usually carries
impulses from the nerve. It is surrounded with the plasma membrane which is a
continuation of cell membrane. It ends in a number of synaptic knobs which
contain vesicles rich in chemical transmitters.
Two types of nerve fibers are found:
(a)Myelinated nerve fibers:
❑The axon is surrounded by a myelin sheath, made by Schwann cells, (important for

rapid conduction of nerve impulse) & outer neurolemmal sheath (important for
regeneration of axon).
❑The myelin sheath is highly insulator to electric currents. It does not form a

continuous layer, but is interrupted at intervals of 1 mm called “Nodes of Ranvier”


which are uninsulated area.
(b) Non-myelinated nerve fibers:
The myelin sheath is absent. The axon is surrounded by Schwann cells.
❖ Excitability:
-It is the ability of living tissues to respond to changes in environment.
-The most excitable tissues in the body are nerves & muscles.
▪Stimulus: It is the change in the environment.
▪Types of stimuli:
Electrical – mechanical – chemical – thermal
Electrical stimulus is preferred because:
1/It is similar to natural stimuli inside the body.
2/It can be controlled.
3/It can be accurately measured.
4/It leaves the tissue undamaged.
▪Method of nerve stimulation:
For electrical stimulation of nerve: 2 stimulating electrodes are put on surface of
nerve fiber: One connected to anode of stimulator & the other is connected to
cathode of same stimulator.
The important element is the cathode which
induces flow of current
*Conductivity: Is the ability of nerve fiber to
propagate impulse.
Strength – duration curve:

- The curve explains the relation


between the strength of stimuli and
duration of application of stimuli
needed to excite tissue.
- Within limits: the stronger the strength the shorter will be the duration
needed to excite tissue and vice versa.
- There is minimum strength needed to excite tissue below which no response
occur. This strength is known as Rheobase.
- There is minimum time needed to excite tissue below which no response
occurs. This time known as utilization time.
- Chronaxie is the time need by 2 Rheobase to excite tissue. It is time factor
used to measure the excitability of the tissues.

Resting Membrane Potential

▪Definition: It is membrane potential difference between inside and outside the


nerve at rest. (i.e. No excitation). It is found in all cells but more marked in nerve
cells & muscle cells.
▪Measurement:
- Two microelectrodes are used: One electrode is placed on surface of fiber
membrane & the other is dipped inside the fiber.
-RMP = - 90 mv in large nerve & skeletal muscle fibers.
= - 70 mv in medium size neurons
▪RMP is caused by:
▪1- Selective permeability (form the majority of resting membrane potential).
2- Sodium – potassium pump.

I - selective permeability:

➢ 1- K+ is the main ion intracellular.


2- Na+ is the main ion extra cellular.
3- K-Na leak channels are present in membrane allowing movement of
both Na and K .
➢ the number of K+ leak channels are ore than the number of Na leak channels
➢ the Ca2+ outside the fibers guard the Na channels and repel Na decreasing
its permeability.
6- K+ is present 35 time inside than outside
5- Na+ is present 10 times outside than inside .
➢ K+ outflow is much greater than Na+ inflow (100 times) because of: smaller
size of K+ than Na+ and high concentration gradient of K+.
➢ Net effect is increase +ve charge outside and –ve charge inside.

II – Sodium –potassium pump:


- Is active and needs ATP
- Na - K pump is a carrier protein in the cell membrane with three
characters:-
1. It has three binding sites on the inside for Na+.
2. It has two binding sites on the outside for K+.
3. The inner part has ATPase activity.
- Na is actively transported out of cell.
- K is actively transported into cell.
- The out ward pumping of 3Na+ is accompanied by inward pumping of 2K+.
N.B if the RMP = -90 mv the selective permiability form -86mv while sodium
potassium pump = -4 mv

Action potential
It is rapid change in membrane potential due to stimulation of nerve fiber by
adequate stimuli

.
I - Ionic change
• During rest: membrane potential = -70 mv.
• Application of stimuli: These stimuli must be threshold to stimulate the
nerve.
• Stimulus artifact which is small oscillation indicates time of application of
stimuli.
• Latent period: This is period between applications of stimuli and beginning
of response.
1. Partial depolarization where membrane potential decrease to -55 mv
due to opening of some voltage gated Na channels and entry of Na+.
2. Firing level at -55 mv all Na channels are opened.
3. Complete depolarization: where membrane potential decrease then
lost then reversal of polarity occur to (+35 mv) due to opening of all
voltages gated Na channels and entry of Na.
4. Repolarization phase where membrane potential return to resting due
to inactivation of Na channels and opening of K channels.
Repolarization process starts rapid then when 70% completed it slow
down. (Repolarization is due to K exit).
5. After depolarization: membrane potential become below resting
level caused by K exit and slow closure of K channels.
6. After hyper polarization: membrane potential return to resting level
by Na – K pump.
NB: step 5 & 6 collectively known as hyperpolarization.
Voltage gated Na channels may be:
- At rest → closed from outside (-90 mV).
- Activated → opened from outside (-90 to +35 mV).
- Inactivated → closed from inside (+35 to -90 mV).
Voltage gated K channels may be:
- At rest → closed from inside (-90 mV).
- Activated → opened (+35 to -90 mV).
II - Excitability change:

• Absolute refractory period the nerve dose not respond to any stimulus in
this period, this period coincide with depolarization phase and first one third
of Repolarization. Its occur due to inactivation of Na channels.
• Relative refractory period: the nerve show weak response in this period. It
coincides with second and third part of Repolarization. It's occur due to
recovery of some Na channel.

Depolarization Repolarization

Membrane potential decrease. Membrane potential return to rest.


Composed of:- partial Composed of: -Rapid part.
depolarization. Slow part.
- complete
depolarization
Ionic change opening of Na Ionic change opening of K
channels. channels.
Form : ascending limb. From: descending limp.
Excitability lost. Increase gradually.
• Properties of action potential:
1- Action potential caused by threshold stimuli.
2- Action potential can be propagated.
3-Action potential obeys all or none law.
4- Action potential cannot be graded.
5-Action potential cannot be summated.
6- Action potential accompanied by ARP.

Difference between action potential and local response:


Local response Action potential
1)Caused by sub threshold stimulus -Caused by threshold or suprathreshold
2)Localized- not conducted -It is propagated
3)Can be graded -Cannot be graded
4)Not obey all or none law -Obey all or non-Law
5)Can be summated -Cannot be summated
6) Not accompanied by absolute -Accompanied by ARP
refractory period (ARP). -Depolarization is complete & reversal
7)Depolarization is partial of polarity

Factors affecting excitability of nerves:


[A]Factors that increase [B]Factors that decrease excitability:
excitability:
(1)Conditions increasing Na+ (1) Conditions decreasing Na+
permeability leading to rapid permeability leading to slow
depolarization: depolarization:
++
a)Low Ca in extracellular fluid. a) High Ca++ in extracellular fluid
b)Veratrine b)Local anesthetics as cocaine
(2)High K+ in extracellular fluid (2)Low K+ in extracellular fluid
Increase K+ extracellular - decrease K+ extracellular →Increase
→decrease K+ efflux - K+ efflux →hyperpolarization
→depolarization.
(3)Local response -This occurs in hereditary disease
known as Familial periodic paralysis:
where hypokalemia leads to decrease
nerve excitability & paralysis. He is
treated by intravenous K+
administration.
Propagation (conduction) of action potential:

The conduction of AP differs whether the nerve is myelinated or not. In


unmyelinated nerve there is local circuit of current flow between the depolarized
area and adjacent resting area lead to its depolarization while in myelinated nerve
because myelin sheath is insulator the action potential jump at node of Ranvier.
Action potential travels along the length of the nerve fiber in both directions.
[1]Propagation in unmyelinated axons: Passive

❑A local circuit of current flow occurs between the depolarized area of the
membrane and the adjacent resting areas i.e. positive charges flow passively to
area of negativity on both outer & inner surface of the membrane.
❑The adjacent areas become depolarized to firing level producing action potential

and so on.
❑The action potential propagated passively with same magnitude.
❑ The propagation speed  square root of fiber diameter.
[2] Propagation in myelinated axons: salutatory conduction

❑Propagation in myelinated axons follows same principle of propagation in


unmyelinated ones.
But: because the myelin sheath is insulator, the action potential generated only at
nodes of Ranvier and the positive charges jump from resting nodes to activating
ones (Salutatory conduction).
❑The propagation speed  fiber diameter  internodal distance.

❑Importance of salutatory conduction:

-Velocity of conduction is 50 times that the velocity in unmyelinated ones.


- Less energy consumption because there is only opening of Na+ channels at nodes
of Ranvier → little extra metabolism for Na+ & K+ concentration establishment by
Na+-K+ pump mechanism.
Types of nerve fibers

A B C
Less than 1
Diameter 2-20 micron 1-5 micron
micron
Velocity 20-120 m/sec 5- 15 m/sec 2 m/sec
Duration spike 0.5 m.sec 1 m.sec 2 m.sec
Myelinated Myelinated
Example Unmyelinated
somatic autonomic
In between A and
Sensitive to Hypoxia, pressure Local anaesthesia
C

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