PHYSIOLOGY Short Note 2

Core 1 ED 3 General Physiology
Edna Adan University
Dr. Abdiaziz Omar

PHYSIOLOGY
- Physiology is the study of normal functions of living organisms. It
includes many branches like viral physiology, bacterial physiology,
cellular physiology, plant physiology, animal physiology and human
physiology.
- Human physiology is the branch of physiology which is concerned
with the functions of the entire human body; from the sub-cellular
components to the organs and organ systems. It is also concerned with
how these functions are performed and how they are integrated.
HOMEOSTASIS
- All living organisms are composed of cells. Cells of the body do not
only contain water, but also surrounded by water (= intracellular and
extracellular fluid compartments). The extracellular fluid is the link
between the external world and the cells. It carries nutrients to the cells
and eliminates their waste products. It circulates between all cells in
the body and provides for them a homogenous environment. In other
words, it is essential for survival of cells. Disturbance of this
extracellular fluid impairs functions of cells and results in disease. For
this reason it is described as the "internal environment" (Claude
Bernard, 19th century). Later on, the term "Homeostasis" was applied.
It indicates that: "all systems in the body, however various, they have
one goal; to maintain the constancy of the internal environment (which
is the ECF)". Therefore each organ in the body participates in
homeostasis by maintaining constant ECF volume, osmolarity, pH,
pressure or temperature).
The core of medical physiology (1) – 3rd edition Page 1

CELL STRUCTURE
- Cells are the building blocks of the body (the basic units of each
tissue). The entire body contains about 75 to 100 trillion cells. Although
these cells are highly specialized in various organs to perform specific
functions, the structures inside their cytoplasm (i.e. the organelles) are
almost identical in all types of cells. These include the following:
 The cell membrane:
- Phospholipid bilayer (about 25%) with proteins (about 50%); plus
some cholesterol (13%), carbohydrates (3%) and other lipids.
- The phospholipids have hydrophilic parts "phosphate" facing
outside and the hydrophobic parts "fatty acids" in the interior of the
membrane.
- Thickness = 7.5 nm (75 Angstrom)
- It is a semi-permeable membrane (allows passage of lipid soluble
substances and prevents passage of water and water soluble ones).
However, the protein channels and carriers in the membrane facilitate
passage of many substances- see below.
- It contains two types of protein:
o Peripheral proteins: attached to one surface of the cell
membrane (usually the inner surface)
o Integral proteins: extends throughout the cell membrane
- Functions of proteins in the cell membrane:
o Offer structural support to the membrane (cytoskeleton)
o Act as adhesion molecules (connect cells together)
o Act as enzymes (catalyze chemical reactions on the cell
membrane)

o Act as antigens (usually glycoproteins; like the blood group
antigens on surface of red blood cells and the “HLA”
antigens (human leukocyte antigens) on surface of all
nucleated cells.
Notes about the HLA antigens:
 They are encoded by group of genes in the short arm (P
arm) of chromosome 6. These genes are known as the
genes of the major histocompatibility complex (MHC). They
include different classes (e.g. MHC class I, MHC class II &
MHC class III).
 HLA antigens (also known as MHC antigens) are unique for
every person; that’s why they are used by the immune
system to distinguish self cells or antigens from non-self
(they are considered in selection of a donor in organ
transplantation).
o Act as ion channels for movement of water and ions
across the cell membrane (osmosis and simple diffusion)
o Act as carriers for passive transport of certain substances
across the cell membrane (facilitated diffusion; see below)
o Act as pumps for active transport of certain substances
across the cell membrane (active transport; see below)
o Act as receptors for hormones and neurotransmitters
 Remember that peripheral proteins act as enzymes
whereas integral proteins carry out the other functions.
 Carbohydrates on the surface of a cell membrane (=
glycocalyx) are either attached to proteins (forming
glycoproteins) or to lipids (forming glycolipids).

Fig 1: The cell membrane
 The nucleus
- Contains chromatin (DNA) which condenses to form chromosomes
before cell division. The DNA replicates during cell division to carry
genetic information from the mother cell to the daughter cells.
- The nucleus also contains one or more nucleoli rich in ribosomal
RNA (the RNA is synthesized from DNA by transcription). The
ribosomal RNA diffuses to the cytoplasm to be translated into proteins
(in the ribosomes of the rough endoplasmic reticulum).
- The proteins may act within the cell or may be packed within vesicles
(in the Golgi apparatus) for secretion to the outside.
 The endoplasmic reticulum
- Complex meshwork of canals and vesicles, extending from the
nucleus to the exterior of the cell.
- Two types:

o Smooth endoplasmic reticulum:
- Has no ribosome on its surface
- For synthesis of lipids and steroids
- Contains enzymes for certain metabolic functions within
the cell (e.g. detoxification of foreign substances)
o Rough endoplasmic reticulum:
- Has ribosomes on its surface
- For protein synthesis
 The Golgi apparatus
- Closely associated with the rough endoplasmic reticulum.
- For processing and package of proteins synthesized in the rough
endoplasmic reticulum into secretory vesicles (most of the packed
proteins act as enzymes).
 The mitochondria
- The power houses of cells (provide the energy used by the cell to
perform its functions). They are abundant in certain cells like endocrine
cells, parietal cells and renal cells (because these cells need energy
for synthesis of hormones or active transport of ions).
- Each mitochondrion is surrounded by two phospholipid bilayer
membranes; the inner one is folded to produce cristae. The cristae and
the inner cavity of the mitochondrion (the matrix) contain the
respiratory enzymes needed for oxidative phosphorylation of glucose
to release large amount of energy in form of ATP (Adenosine
diphosphate).
- Each mitochondrion contains DNA that plays a role in formation of
few intra-mitochondrial proteins (using mitochondrial ribosomes) and
in its own replication.

- Abnormalities of mitochondrial DNA may result in certain diseases,
usually affecting the high energy tissues (muscle, heart and brain).
These diseases are always inherited from mothers (this is because the
defective mitochondria are inherited through ova of mothers; whereas
sperms of fathers do not contain mitochondria).
 The lysosomes
- Vesicles formed from the endoplasmic reticulum and Golgi
apparatus. They contain hydrolytic enzymes (proteases, lipases,
carbohydrases & nucleases) that are used in hydrolysis or digestion
of engulfed material (e.g. digestion of bacteria within vacuoles of the
white blood cells).
Fig 2: The cell organelles

TRANSPORT MECHANISMS ACROSS CELL MEMBRANES
- There are constant movements of O2, CO2, nutrients, electrolytes
and waste products across cell membranes. A variety of transport
mechanisms are involved, these are generally classified into passive
and active transport mechanisms.
 Passive transport mechanisms:
- Do not consume energy in transport.
- Transport substances from areas of higher concentration to
areas of lower concentration (i.e. down the concentration or
electrical gradient).
- Either do not use carrier (= simple diffusion) or use carrier (=
facilitated diffusion).
 Active transport mechanisms:
- Consume energy in transport.
- Transport substances from areas of lower concentration to
areas of higher concentration (i.e. against the concentration or
electrical gradient).
- Always need carrier for transport.
- Transport of a substance against its chemical or electrical gradient,
with consumption of energy and usage of a carrier is known asprimary
active transport.
- Transport of a substance with an other one that’s transported
actively is known as secondary active transport. Here the substance
uses the same carrier that’s used by the other substance.
- Secondary active transport (also known as co-transport) may occur
in the same direction of the primary substance (= symport), or in the
opposite direction (= antiport).

 Substances transported by simple diffusion
- Diffusion is the process by which a substance expands, because of
the random movement of its particles to fill the available volume.
- Non-polar substances transported by simple diffusion include:
o Fatty acids
o Steroid hormones (synthesized from cholesterol)
o Gases (O2 and CO2)
- Simple diffusion of polar substances (water soluble substances) like
ions is low. However, it can occur through certain "ion channels"
(integral proteins in the cell membrane).
- Passive diffusion of water through cell membranes is known as
osmosis. It occurs through certain water channels known as
aquaporins. Water moves from the side of lower concentration of a
solute to the side of higher concentration of the solute.
Fig 2: Passive transport

 Substances transported by facilitated diffusion
- Do not consume energy in the process of transport.
- Have a maximum rate of transport that depends on the density of
carriers on the cell membrane. The maximum rate is reached when
all the carriers are saturated.
- Examples include transport of glucose through the basolateral
membranes of renal and intestinal cells and its absorption from the
ECF by most cells of the body.
Substances transported actively
- The well known example of primary active transport is the pump that
transports sodium and potassium against their concentrations (= The
Na+ / K+ pump). It transports three atoms of sodium from ICF to ECF
in exchange to two atoms of potassium from ECF to ICF.
Fig 3: Active transport

- The well known example of secondary active transport is the
transport of glucose (coupled to sodium) through the luminal
membranes of intestinal and renal cells.
- Secretion of hydrogen by renal cells is another example of
secondary active transport. However, hydrogen moves in theopposite
direction to sodium (anti-port).
 Other transport mechanisms

o Endocytosis (active vesicular transport)
- Endocytosis is the uptake of molecules into cells. Here a molecule
fuses with the cell membrane, invaginates it and then the invagiation
is separated from the cell membrane to form of a vesicle.
- Special proteins may facilitate the process of endocytosis (clathrin
and dynamin).
- When the engulfed substance is dissolved in fluid, the process is
known as pinocytosis (cell drinking); and when it is a particulatematter
or bacteria, the process is known as phagocytosis (cell eating).
o Exocytosis (active vesicular transport)
- Exocytosis is the release of substances from cells. (i.e. opposite to
endocytosis). Proteins synthesized within the cell are usually packed
into secretory vesicles and secreted by exocytosis.
- Notice that exocytosis requires calcium, energy and certain
proteins.
o Solvent drag (passive transport)
- During diffusion of a solvent, it tends to drag some solute with it. This
occurs in capillaries.

Fig 3: Endocytosis & Exocytosis
 Transport proteins "carriers, pumps & ion channels"

- These are highly specialized transmembrane proteins that allow
passage of water, ions, glucose, urea and other substances through
cell membranes.
- The carriers change their shape (configuration) when they bind their
substances to move them from one side of the cell membrane to the
other side, usually down the chemical or electrical gradients (=
facilitated diffusion).
- The pumps act as ATPase enzymes to catalyze hydrolysis of ATP.
The released energy is used in active transport of substances, against
their chemical or electrical gradients. Examples include the Na+/ K+
ATPase pump, the proton pump and the Ca2+ ATPase pump.

(Remember that the active transport is either primary active or
secondary active, see above).
- The ion channels allow simple diffusion (down chemical or
electrical gradients). They include:
 Leak channels
- Always open
- Example: Potassium leak channels which are responsible
for the resting membrane potentials
- Resting membrane potentials are found in almost all cells
in the body (see chapter two)
 Voltage gated channels
- Have gates that open or close in response to changes in
voltage "or potential" in the cell membrane
- Examples: voltage gated sodium channels & voltage
gated potassium channels which are responsible for the
depolarization and the repolarization phases of action
potentials respectively
- Action potentials are only found in excitable tissues (nerve
and muscle)
 Ligand gated channels
- Have gates that open when certain membrane receptors
bind to specific neurotransmitters or hormones, and close
when these chemicals are released from the receptors
 Mechano-sensitive channels
- Have gates that open in response to direct mechanical
stimulation of the cell membrane
- They are involved in movement of some cells

QUESTIONS FOR SELF ASSESSMENT-1 (BEST OF FIVE)
1- Concerning the cell organelles:
a. mitochondria synthesize proteins
b. endoplasmic reticulum is needed for cell division
c. nuclei are the power houses of cells
d. lysosomes contain hydrolytic enzymes
e. Golgi apparatus translates RNA into proteins
2- Water passes through cell membranes by:
a. facilitated diffusion
b. primary active transport
c. osmosis
d. co transport
e. none of the above
3- Maintenance of constant internal environment is known as:
a. endocytosis
b. feedback mechanism
c. physiology
d. homeostasis
e. haemostasis
4- Facilitated diffusion:
a. occurs against the electrical gradient
b. requires energy
c. not influenced by the concentration gradient
d. has no transport maximum capacity
e. mediated by a protein carrier
5- Which of the following can cross the cell membrane passively?
a. Proteins
b. carbon dioxide
c. potassium ions
d. calcium ions
e. glucose
6- Facilitated diffusion differs from simple diffusion in that it:
a. does not require energy
b. occurs against the electrical gradient
c. is not influenced by the concentration gradient
d. is mediated by a protein carrier
e. has no transport maximum capacity
7- Which of the following is a passive type of transport:
a. solvent drag
b. endocytosis
c. exocytosis
d. co-transport
e. antiport

8- Concerning transport of ions across cell membranes, which of
the following is not true:
a. secondary active transport requires energy
b. simple diffusion occurs down the concentration gradient
c. facilitated diffusion occurs against the electrical gradient
d. active transport is mediated by a protein carrier
e. secondary active transport has a transport maximum capacity
9- Concerning transport across cell membranes, all the following
require integral proteins to cross cell membranes except:
a. water
b. glucose
c. oxygen
d. potassium ions
e. calcium ions
10- Leak channels:
a. are present in almost all cells in the body
b. have gates that open or close in response to changes in potential
c. open when a hormone binds to a nearby membrane receptor
d. are responsible for the depolarization phase of action potentials
e. are activated by mechanical stimulation of cell membranes
11- All of the following substances cross the cell membrane
through channels or transporters except:
a. sodium
b. bicarbonate
c. oxygen
d. water
e. potassium
12- Homeostasis is:
a- arrest of bleeding
b- maintenance of constancy of the external environment
c- formation of a blood clot
d- normal pH
e- represented by control of body temperature

CHAPTER 1
BODY FLUIDS
TOTAL BODY WATER (TBW)
-Body composition in a 70 Kg young adult male:
– Water = 60% (of the total weight which is 70 kg)
– Proteins = 18%
– Fats = 15%
– Minerals = 7%
– Carbohydrates < 1%
-Therefore: water is the most important constituent in the body.
-With total deprivation of water, survival is limited to a few days,
whereas total food deprivation is tolerated for at least a month.
-Total body water (in a 70 kg, young adult male):
= 60 % of the total body weight
= 42 Kg (60/100 x 70) = 42 L (because density of water = 1)
 Variation in the % of TBW among different subjects
-The % of TBW varies according to:
1) Age
- TBW decreases with age (e.g. in an embryo it is near to100%,
in a neonate = 80%, in an adult male = 60% and above the age
of 60 years = 52% in males).
2) Sex
- The % of TBW is higher in males when compared to equivalent
females. This is because the female has higher percentage of fat
in her body, compared to an equivalent male, with the same age
and weight.

- The higher percentage of fat is associated with less
percentage of water because fat cells contain less water than
other types of cells. For example, water in a fat cell is about 13%
whereas in a muscle cell is about 75%.
3) Body size
- The % of TBW is higher in thin-tall subjects compared to obese-
short subjects.
- This is also explained by the higher percentage of fat in the
obese subject, and therefore less percentage of water.
Table1.1: % of TBW in males and females of different ages

Age % of water in a male % of water in a female
Embryo Almost 100% Almost 100%
Neonate 80% 80%
Adult 60% 51%
Elderly 52% 46%
 Body Fluid Compartments

- As mentioned in the introduction of this book, cells of the body do
not only contain water, but also surrounded by water.
- Therefore, total body water is divided into two compartments:
– 1) Intracellular fluid (ICF): = 2/3 of the total body water or 40%
of the total body weight (TBwt).
– 2) Extracellular fluid (ECF): = 1/3 of the total body water or 20%
of the total body weight (TBwt).
- ECF is further divided into:
– a) Interstitial fluid: = 75% of ECF or 15% of TBwt.

– b) Intravascular fluid (plasma): = 25% of ECF or 5% of TBwt.
– c) Trans-cellular fluid: Negligible.
Notes about trans-cellular fluid:
 It includes synovial fluid, pleural fluid, pericardial fluid,
peritoneal fluid, cerebrospinal fluid...
 Its volume is very low, that’s why it is not included in
calculations of ECF.
 In abnormal conditions (like pleural effusion, pericardial
effusion and ascites) its volume becomes very high.
- In a 70 Kg adult male:
– Total body water = 42 L (60% of the total body weight)
• ICF = 28 L (= 40% of total body weight)
• ECF = 14 L (= 20% of total body weight)
– ISF = 10.5 L (= 15% of total body weight)
– IVF (Plasma) = 3.5 L (= 5% of total body weight)
Question: Calculate the expected body fluid compartments in an
average 60 kg adult male
Answer: Total body weight= 60Kg, therefore: Total body water =
60/100 x 60 = 36L, ICF = 40/100 x 60 = 24 L, ECF = 20/100 x 60 =
12 L, ISF = 15/100 x 60 = 9 L and IVF = 5/100 x 60 = 3 L.
Notes about body fluid compartments in neonates:
 Total body water constitutes a very high proportion of the total
body weight (about 80%)
 ECF exceeds 30% and ICF volume is less than 40% of total
body weight. Therefore, ECF/ICF volume ratio is very high

 Differences between ECF & ICF:
 ECF has: lower volume, higher pH and higher concentrations of
sodium, calcium, chloride & bicarbonate. Sodium is the main
cation and chloride is the main anion.
 ICF has: higher volume, lower pH and higher concentrations of
potassium, magnesium, phosphate, sulphate and protein.
Potassium is the main cation and non-diffusible anions (like
organic phosphate and protein) are the main anions.
Table 1.2: Differences between ECF and ICF in a 70 kg adult male
Difference Extracellular fluid Intracellular fluid
Volume 15L 25L

Conc. Of Cations:
Sodium (Na+) 142.0 mmol/L 10 mmol/L
Potassium (K+) 4.0 mmol/L 140 mmol/L
Calcium (Ca+2) 2.5 mmol/L Negligible (0)
Magnesium (Mg+2) 2.0 mmEq/L 26 mmEq/L
Conc. Of Anions:
Chloride (Cl-) 105.0 mmol/L 4 mmol/L
-
Bicarbonate (HCO3 ) 25.0 mmol/L 10 mmol/L
-3
Phosphate (PO4 ) 2.0 mEq/L 100 mEq/L
Protein 17.0 mEq/L 65 mEq/L
pH 7.4 7.2
Temperature 37 c 37 c
Osmolarity 280-300 mOsm/L 280-300 mOsm/L

 Measurement of body Fluid Compartments
- Volumes of body fluid compartments can be measured using the
indicator (dye) dilution method.
- In this method, a known quantity of a substance (e.g. a dye) is
injected and allowed to distribute in the compartment of interest. After
distribution, a sample of fluid is taken from the same compartment to
measure the final concentration of the dye. Then the volume of the
compartment (known as the volume of distribution of the dye) is
calculated using the formula:
Volume of distribution = Q-e /C
Where:
- Q is the quantity of the dye injected
- e is the amount of the dye excreted or metabolized by cells
- C is the concentration of the dye after equilibration
- Substances used for measurement of body fluid compartments
should have the following characteristics:
- Non toxic
- Easily measured
- Their amounts are not altered by the body (not stored,
metabolized, excreted or produced by the body) or the
altered amount can be calculated easily
- Distribute only in the compartment being measured
- Do not affect water distribution in other compartments
Remember that:
 Leakage of a substance into other compartment decreases its
final concentration and therefore increases the calculated
volume of distribution.

Examples for substances used in measurement of body fluids:
Substances used in measurement of total body water:
-Deuterium oxide (heavy water)
-Tritium oxide (3H2O = an isotope of water)
-Antipyrine
-Aminopyridine
Substances used in measurement of extracellular fluid:
-Saccharides (inulin, manitol & sucrose)
These fail to penetrate the trans-cellular fluid
Therefore they underestimate the ECF
-Radioactive electrolytes (sodium, chloride & bromide)
These easily penetrate the entire ECF and may
escape into cells
Therefore they overestimate the ECF
-Thiosulphate & thiocynate
Substances used in measurement of plasma:
-Radioactive iodine used to label serum albumin (RISA)
-Evan’s blue dye (which binds to plasma protein and stay in
plasma)
-Labeled macroglobulin
Substances used in measurement of Blood:
-Blood volume can be calculated from plasma and packed cell
volume (PCV) by the formula: Blood = Plasma X 100/100-PCV
-The PCV is measured by centrifugation of a sample of blood in
a capillary tube, and then the percentage of the packed cells
at the bottom of the tube is calculated (read about the PCV in
chapter 5).

-It is also calculated from red blood cell volume and plasma
volume by the formula: Blood = plasma + red blood cell volume.
-The red blood cell volume is obtained from the volume of
distribution of re-injected red blood cells labeled with
radioactive chromium (51Cr).
Intracellular fluid and interstitial fluid:
- Are measured indirectly by two substances, for two
compartments. Then ICF or ISF can be subtracted as follows:
ICF = TBW - ECF
ISF = ECF - plasma
Factors Affecting Body Fluid Compartments

Body fluid compartments are affected by:
1. Osmosis
2. Diffusion
3. Gibbs Donnan equilibrium
4. Sodium-potassium pump
5. Starling's forces
6. Abnormalities of water balance
1- Osmosis
- Osmosis is the movement of water molecules across a semi-
permeable membrane, from a region of lower concentration of asolute
to a region of higher concentration of the solute (see theintroduction).

- All cell membranes and capillaries are semi-permeable membranes
(permeable to water and generally not permeable to solute).
- For osmosis to occur there should be a difference in solute
concentration between the two sides of the membrane, i.e. difference
in osmolarity.
Fig 1.1: Osmosis
1
Solution A has the same
concentration as solution B
= No osmosis
2
Solution A has higher
concentration than solution B
= Osmosis from B to A
Osmolarity, Osmolality & Tonicity

Osmolarity
- Osmolarity is the number of osmoles of solute per one liter of
solution.
- It is used to describe concentrations of osmotically active particles in
a solution.
- If a solute dissociates into ions to form an ideal solution, each
liberated ion is an osmotically active particle.

- For example: dissociation of one mole of (NaCl) gives one osmole of
sodium and one osmole of chloride (i.e. 2 osmoles).
- However, one mole of glucose (C6H12O6) in a solution gives one
osmole; because organic substances like glucose are non-ionizable.
- Remember that one mole of a substance contains the same number
of molecules that are found in one mole of any other substance (=
Avogadro's number = 6.061 x 1023).
- The osmotically active particles can exert osmotic pressure if they
are in contact with another solution, but separated from it by a semi-
permeable membrane (permeable to the solvent but not to the solute).
- Osmotic pressure is defined as the pressure necessary to prevent
solvent migration (i.e. prevent osmosis).
Fig 1.2: The osmotic pressure
Osmotic pressure prevents

osmosis from solution B to
solution A

Osmolality
- Osmolality is the number of osmoles per one kilogram of solvent.
- It is more accurate than osmolarity since it depends on mass (which
is constant) rather than volume (which is affected by changes in
temperature and pressure).
- In body fluids, where the solvent is water, the concentration of solutes
is very low (highly diluted); therefore one liter and one kilogram are
equal. More over, temperature and pressure are constant under
normal physiological conditions; that’s why osmolality and osmolarity
are equal in body fluids.
- Because of this similarity between osmolality and osmolarity, you may
find osmolality expressed in (mosm/L) rather than (mosm/Kg).
- Osmolality of plasma = (280-300) mosm/L. Na+ and its anions are
responsible for most of this value (Na+ determines ECF osmolality).
- Osmolality of intracellular fluid = (280-300) mosm/L. K+ and its anions
are responsible for most of this value (K+ determines ICF osmolality).
Tonicity
- This term is used when describing osmolality of a solution relative to
osmolality of the plasma.
- Accordingly, solutions may be:
o Isotonic (with osmolality similar to plasma)
o Hypotonic (with osmolality lower than plasma)
o Hypertonic (with osmolality higher than plasma)
- Intravenous (I.V.) infusion of each type of these solutions affects
volumes and osmolarities of body fluid compartments. These effects
can be studied from the following figure and table:

Fig 1.3: The effects of different types of solutions on cells:
Table 1.3: Effects of I.V. solutions on volumes and osmolarities

ECF ICF
Solution Osmosis
Vol. Osmol. Vol. Osmol.
Isotonic The same The same The same
Hypotonic
Hypertonic
- From the above table:

- I.V. infusion of an isotonic solution increases volume of ECF
with no effect on its osmolarity, and no effect on volume or
osmolarity of ICF (i.e. no effect on cells).
- I.V. infusion of a hypotonic solution increases volumes of ECF
and ICF and decreases osmolarities of ECF and ICF.
- I.V. infusion of a hypertonic solution increases volume and
osmolarity of ECF, and decreases volume of ICF while its
osmolarity is increased.

Calculation of osmolality:
A. From the Freezing Point Depression
- One osmole depresses the freezing point of a solution by 1.86 οc
- One milliosmole depresses the freezing point by 0.00186 οc
- Number of milliosmoles per liter in a solution =
The freezing point depression/0.00186
Q: Calculate the osmolality of normal human plasma if the freezing
point = - 0.55 οc
Answer: Plasma osmolality = 0.55/0.00186 = 295 mosm/L
B. From the Molarity

Number of osmoles = Number of moles x number of particles
(liberated by a single molecule)
Q: Calculate the osmolarity of 0.9% NaCl solution and mention the
effect of this solution on volume and osmolarity of ICF after its infusion
in the plasma? (Molecular weight of NaCl = 58.5).
Answer: 0.9% NaCl = 0.9 g/dL, (x 10) = 9 g/L
Molarity = [conc. g/L] / MWt of NaCl = 9 / 58.5 mol/L
= 0.154 mol/L, (x 1000) = 154 mmol/L
Osmolarity = 154 x 2 = 308 mosm/L
(Isotonic, has no effect on ICF)
(Remember that: This solution is regarded as isotonic solution
although its osmolarity is higher than plasma Osmolarity (> 300
mosm/L). This is because the dissociation of NaCl in plasma is not
as complete as in true ideal solutions (dissociation is about 93%).
Therefore the osmolarity of 0.9% NaCl solution in plasma is actually
less than 308 mosm/L; that’s why it is isotonic).

Q: Calculate the osmolarity of 5% glucose solution. If one liter of this
solution is infused intravenously, mention the immediate and the later
effects on the cells? (MWt glucose = 180).
Answer: 5% glucose = 5g/dL = 50 g/L
Molarity = [Conc. g/L]/MWt
= 50/180 = 0.278 mol/L
(x 1000) = 278 mmol/L
Osmolarity = 278 x 1 = 278 mosm/L (Isotonic)
Immediate effect on cells: no effect because it is isotonic
Later effect on cells: After uptake of glucose by cells the solution
becomes hypotonic; water enters cells, it increases volume &
decreases osmolarity of ICF.
Q: Calculate the osmolality of a solution containing 110 mmol NaCl,

25 mmol NaHCO3, 2.5 mmol CaCl2, 5 mmol urea & 5 mmol glucose
Answer: Plasma osmolality = (110x2) + (25x2) + (2.5x3) + (5x1) +
(5x1) = 287.5 mosm/L.
(Remember that glucose and urea are non-ionizable).
C. Using a formula
Osmolarity of the plasma can be calculated using the following
formula: Plasma Osmolarity = 2([Na] + [K]) + [glucose] + [urea]
(All concentrations are in mmol/L)
Q: Calculate the osmolarity of the plasma if [Na] = 140 mmol/L, [K] =
4 mmol/L, [Glucose]= 5 mmol/L and [Urea]= 7 mmol/L.
Answer: Osmolarity = 2(140 + 4) + 5 + 7
= 300 mosm/L (isotonic).

2- Diffusion
- It is expansion or passage of a substance through a cell membrane
down its chemical or electrical gradient, due to continuous random
movement of its molecules.
- Water follows osmotically active particles to inside or to outside the
cell, this affects volumes of body fluid compartments.
Fig 1.4: Diffusion
3- Gibbs Donnan equilibrium

- The presence of non-diffusible anions (protein and organic
phosphate) within the cell affects distribution of diffusible ions (both
anions and cations); it allows entry of diffusible cations (e.g. Na +) into
the cell and prevents entry of diffusible anions (e.g. Cl-).
Fig 1.5: Gibbs Donnan equilibrium

- The concept was shown theoretically by Gibbs and confirmed
experimentally by Donnan (= known as Gibbs Donnan equilibrium).
- At equilibrium:
1- Total cations = total anions (on either side of the membrane)
2- The product of diffusible ions on one side equals the product of
diffusible ions on the other side of the membrane (This holds for
cations and anions of the same valence).
- Take this example of two solutions “a” and “b”; in which Na+ and Cl-
are diffusible cations and anions respectively; X- indicates non
diffusible anions.
Solution (a) Solution (b)
Na+ Na+
Cl- Cl-
X-
At equilibrium:
1- [Na+]a = [Cl-]a + [X-]a (i.e. cations in a = anions in a)
[Na+]b = [Cl-]b (i.e. cations in b = anions in b)
2- [Na+]a x [Cl-]a = [Na+]b x [Cl-]b
[Na+]a/ [Na+]b = [Cl-]b / [Cl-]a
From the above relationships:

 [Na+]a > [Cl-]a
(Cations on the side of X- are greater than anions on the same side)
 [Cl-]a < [Cl-]b
(Diffusible anions on the side of X- are less than on the other side)
 [Na+]a > [Na+]b
(Cations on the side of X- are greater than cations on the other side)

 [Na+]a + [Cl-]a + [X-]a> [Na+]b + [Cl-]b
(There is greater number of ions on the side of X- than on the other
side).
Remember that:
 The greater number of particles in compartment “a” exerts an
osmotic effect resulting in swelling of this compartment.
 A similar effect occurs in body fluids, i.e. cells tend to undergo
swelling but this is prevented by the Na+/K+ pump.
Effects of Donnan equilibrium in the body:

1- Swelling of cells
The ICF contains higher concentration of non diffusible anions than the
ECF and therefore more particles. This may result in swelling of the
cells and eventually their rupture. However, swelling of cells is
prevented by the action of the Na+/K+ pump and other ion channels.
The Na+/K+ pump transports 3 sodium ions to outside of the cell and
2 potassium ions to inside; this decreases the total number of ions
inside the cell and prevents its swelling (see below).
2- Electrical difference across the cell membrane
The asymmetrical distribution of diffusible ions across the cell
membrane generates an electrical difference that can be determined
for each ion by the Nernst equation. In addition the asymmetrical
distribution of non diffusible anions participates in genesis of theresting
membrane potential (see chapter two).
3- Slight difference in concentration of ions between plasma and ISF
Since plasma contains higher concentration of protein than the
interstitial fluid (ISF), it contains slightly higher concentration of

cations (like sodium and potassium) and lower concentration of anions
(like chloride and bicarbonate).
4- Slight difference in concentration of ions between the plasma and
the glomerular filtrate
At the kidney, proteins are not filtered out of the glomerular capillaries.
The filtrate is free of plasma protein. Therefore the plasma contains
slightly higher concentration of cations (like sodium and potassium)
and lower concentration of anions (like chloride and bicarbonate) than
in the filtrate.
Table 1.2: Differences between plasma and ISF in an adult male
Difference Plasma Interstitial fluid
Volume 5% of body weight 15% of body weight

Conc. Of Cations:
Sodium (Na+) 145 mmol/L 140 mmol/L
Potassium (K+) 4.1 mmol/L 4 mmol/L
Calcium (Ca+2) 2.5 mmol/L 2.1 mmol/L
Magnesium (Mg+2) 1 mmol/L 1 mmol/L
Total cations 152.6 mmol/L 147.1 mmol/L
Conc. Of Anions:
Chloride (Cl-) 105 mmol/L 110 mmol/L
-
Bicarbonate (HCO3 ) 25 mmol/L 30 mmol/L
-3
Phosphate (PO4 ) 1 mmol/L 1 mmol/L
Organic acids 5 mmol/L 5 mmol/L
Protein 16.6 mmol/L 1.1 mmol/L
Total anions 152.6 mmol/L 147.1 mmol/L

4- The Sodium-Potassium Pump
- Found in all cells of the body.
- Transports sodium and potassium actively against their chemical
gradients (3 Na+ ions to outside and 2 K+ ions to inside the cell).
Fig 1.6: The sodium potassium pump
- It accounts for 20-45% of the total metabolic energy expended by the

cell.
- Consists of alpha and beta subunits extending through the cell
membrane. The beta subunit is a glycoprotein, whereas the alpha
subunit is a protein with extracellular binding sites for K+ and
intracellular binding sites for Na+ and ATP.
Fig 1.7: Subunits of the sodium potassium pump

- It is the alpha subunit that transports Na+ and K+; however,
separation of the two subunits inactivates the pump
- The Na+/K+ ATPase enzyme releases energy from ATP that’s used
in transport of 3 sodium ions to outside the cell and 2 potassium ions
to inside. This results in accumulation of negative charges inside the
cell (i.e. it is an electrogenic pump).
Functions of the Na+/K+ pump
- Participates in genesis of the resting membrane potential (i.e.
generates negative charges towards the inner side of the cell
membrane (see chapter two)).
- Prevents swelling and rupture of cells by removing excess sodium
ions to outside (see Donnan effect).
Regulation of the pump
- The pump is activated by accumulation of Na+ ions intracellularly.
- Activity is increased by:
o Insulin, Aldosterone and thyroid hormones
- Activity is inhibited by:
o Dopamine and digitalis
5- Starling's forces
- As mentioned above, movement of water across cell membranes
depends on osmosis. However, movement of water across the walls
of capillaries depends, in addition to that, on 4 primary forces (known
as Starling’s forces) that control fluid exchange between plasma and
interstitium.
- Although Starling’s forces act in all blood vessels, they cause fluid
exchange only in capillaries.

- This is because the walls of capillaries, unlike arteries and veins,
are characterized by pores between the endothelial cells that allow
movement of water (for this reason capillaries are called “the exchange
vessels”).
- Starling forces include:
1- Capillary hydrostatic pressure (HPc)
- It is the pressure of plasma acting on the lateral wall of the
blood vessel
- For filtration (from plasma to ISF)
= 35 mmHg at the arteriolar end of capillaries
= 15 mmHg at the veniolar end of capillaries
2- Capillary oncotic pressure (OPc):
- The osmotic pressure of plasma proteins (also known as
colloid osmotic pressure or oncotic pressure)
- It is exerted mainly by albumin
- For absorption (from ISF to plasma)
= 25 mmHg throughout the capillaries (proteins are not filtered
and therefore their oncotic pressure is not changed)
3- Interstitial fluid hydrostatic pressure HPISF:
- Acts in the opposite side to HPC;(i.e. against filtration)
4- Interstitial fluid oncotic pressure OPISF:
- Acts in the opposite side to OPC; (i.e. against absorption)
Notes about osmotic pressure of proteins (Oncotic pressure)
 Oncotic pressure is mainly exerted by albumin because it is the
smallest plasma protein and therefore it has the highest
number of particles than other types of plasma proteins.
 Osmolarity depends on “number” not “size” of particles.

- Calculation of filtration pressure:
- Both hydrostatic pressure of ISF and oncotic pressure of ISF are of
low magnitude, they act against each other and therefore they cancel
each other. That’s why they are not considered in calculation of the
filtration pressure.
- The filtration pressure is calculated by subtracting the capillary
oncotic pressure from the capillary hydrostatic pressure as follows:
o At the arteriolar end= (35-25)= +10 mmHg (i.e. net filtration)
o At the veniolar end= (15-25)= -10 mmHg (i.e. net absorption)
Fig 1.8: Starling's forces
- A filtration pressure of + 10 mmHg indicates that Starling’s forces

cause filtration of plasma at the arteriolar end of capillaries to the
interstitium. The filtered plasma carries nutrients to the surrounding
cells & then the fluid is absorbed back at the veniolar end with the
waste products.

 About 90% of the filtered fluid at the arteriolar end of capillaries is
absorbed back to the capillaries at their veniolar end; the remaining
10% of the filtered fluid is also absorbed but by the lymphatics.
 The lymphatic vessels also absorb small amount of protein that may
escape out of the plasma to the interstitium.
 The lymphatics return this protein together with the 10% of the
filtered fluid back to the circulation at the neck where the main
lymphatic duct drains into the jugular vein. This keeps balance
between filtration and absorption of fluid at the capillaries.
 Disturbance of this balance between filtration and absorption may
result in accumulation of fluid in the interstitium causing edema.
Edema
- Edema is defined as abnormal accumulation of fluid in the interstitial
space. It is caused by many diseases through one or more of the
following mechanisms:
1- Increased capillary hydrostatic pressure (HPC)
- Some diseases may cause accumulation of blood in veins; thus
increasing the HPC at the veniolar end of capillaries.
- When the HPC becomes higher than the OPC , the return of the
filtered fluid to the capillaries is prevented causing edema.
- Examples include:
o Heart failure
 Left sided heart failure results in accumulation of blood in
the lung veins causing pulmonary edema whereas right
sided heart failure causes accumulation of blood insystemic
veins causing generalized edema.

o Venous obstruction
 Results in accumulation of blood proximal to the site of
obstruction causing localized edema
Remember that:
 Oedema is not caused by hypertension because the hydrostatic
pressure of capillaries is not increased at the veniolar end of
capillaries, which is the site of absorption
 Oedema is not caused by arterial obstruction because this
decreases blood flow to the capillaries and therefore decreases
HPC
2- Decreased oncotic pressure (OPC)

- Some diseases may lower the level of proteins in the plasma. This
decreases OPC.
- The low OPC prevents absorption of the filtered fluid back to the
intravascular space causing edema.
- Examples include:
o Malnutrition
 Decreased protein intake (e.g. Kwashiorkor)
 Results in generalized edema
o Malabsorption
 Decreased absorption of protein (e.g. due to chronic
pancreatitis)
o Liver disease (chronic disease like liver cirrhosis)
 Decreased synthesis of plasma proteins

o Renal disease (nephrotic or nephritic syndromes or renal failure)
 Loss of plasma proteins in urine
3- Lymphatic obstruction
- Obstruction of lymphatics results in accumulation of the fluid that’s
supposed to be absorbed by the lymphatics to be removed from the
interstitium. Therefore, it accumulates causing edema.
- The obstruction is caused by:
o Filaria (worms that live within the lymphatic vessels)
 Filariasis results in localized edema (very large swelling
proximal to the site of obstruction known as elephantiasis)
o Surgical removal of lymph nodes (which drain a site of cancer)
 This is done to prevent spread of secondaries from the
cancer
o It interrupts the lymph flow resulting in localized edema
4- Increased permeability of capillaries:

- Some diseases may increase the permeability of capillaries and
allow filtration of plasma proteins to the interstitium thus increasing
the OPISF which absorbs fluid to the outside causing edema.
- The capillary permeability is increased by:
o Inflammation
 The increased permeability is due to mediators of
inflammation released by white blood cells and the nearby
tissues
 Results in localized edema

o Burn
 The increased permeability is due to the high temperature
 Results in localized edema
o Allergy
 The increased permeability is due to histamine which is
released by mast cells and basophils
 Results in localized or generalized edema
Types of edema:
- Edema can be classified into 2 types (by applying pressure on it in
one site using one finger “the thumb” against bone, for a minute):
1- Pitting edema
- The finger leaves a mark (a pit) on the skin
- The mark appears because the fluid escapes away from the
site of pressure and returns slowly
- Causes of pitting edema include:
 All causes of high capillary hydrostatic pressure
 All causes of low capillary oncotic pressure
2- Non pitting edema
- The finger does not leave a mark on the skin because the
escaped fluid returns rapidly.
- This is because it is attracted by proteins that are filtered to
the interstitium
- Causes of non pitting edema include:
 All causes of increased permeability
 All causes of lymphatic obstruction

6- Abnormalities of water balance
 Water balance
- In normal physiological conditions, the body loses water in urine to
excrete waste products of metabolism and in addition to that, there is
insensible loss of water through the skin and in expired air.
- These water losses should continuously be replaced by water intake
to maintain normal water content of the body.
- On the other hand, if water intake is higher than the daily
requirement of the body, the excess water should be excreted.
- In summary: water loss should equal water intake (= water balance)
Fig 1.9: Water balance
- Abnormalities of this balance between water intake and outputcause

disturbances in volumes and osmolarity of body fluid compartments.

Normal water intake occurs through:
o drinking 1.3L/day
o solid food 0.9L/day
o metabolism 0.3L/day
Net = 2.5L/day
Normal water output occurs through:
o urine 1.5 L/day
o stool 0.1 L/day
o sweating & insensible loss 0.9 L/day
Net= 2.5 L/day
Note
- The average water intake = the average water loss = 2.5 L/day
- The above values vary greatly in different physiological and
pathological conditions:
Examples of the physiological conditions:

1- Type of work
E.g. heavy work increases sweating= increased water loss
2- Exercise
E.g. strenuous exercise increases sweating and causes
hyperventilation (increases insensible water loss in expiredair)
= increased water loss
3- Degree of water intake
Affects urine volume as follows:
- High water intake increases urine volume
- Low water intake decreases urine volume
 Remember that the minimum volume of urine required for
excretion of waste products of metabolism is 500 ml/day

4- Variation in body temperature and environmental temperature
Both affect the amount of sweating, the rate of metabolism
and the rate of respiration (see chapter 4)
Examples of the pathological conditions:

1- Abnormal water intake through:
- increased metabolism (fever, hyperthyroidism)
- increased drinking (psychogenic polydypsia)
- excess intravenous fluids (fluid overload)
- complete water deprivation
2- Abnormal water loss through:
- vomiting
- diarrhea
- polyuria (diabetes mellitus, diabetes insipidus)
- excessive sweating (heat exhaustion)
- hyperventilation (metabolic acidosis)
Regulation of water balance

- As mentioned earlier, maintenance of constancy of ECF is the goal
of all systems in the body.
- Variation in water intake or water loss produces minor changes in
extracellular fluid volume and osmolarity. These changes stimulate
certain receptors (e.g. volume receptors & osmoreceptors) that
activate multiple regulatory mechanisms to restore back the constancy
of the ECF.

- The regulatory mechanisms include:
1- Mechanisms for control of water intake
- act principally through control of thirst
2- Mechanisms for control of water loss
- act principally through control of urine volume
Control of water intake

- Under normal environmental and physiological conditions, the
amount of water gained by metabolism or solid food is almost constant
whereas the amount gained by drinking may be variable. That’s why
water intake is generally regulated through regulation of drinking (=
regulation of thirst). On the other hand, water intake through solid food
and metabolism is a non-regulatory component.
Thirst
- Defined as the subjective perception that provides the urge for
humans and animals to drink fluids.
- Also defined as the conscious desire for water.
- Regulated by thirst center located in the hypothalamus.
- There are 4 major stimuli to thirst:
 Angiotensin II: This is an octa-peptide hormone produced in the
plasma following release of renin enzyme from the "Juxta-
glomerular apparatus" in the kidney (see below).
- It acts directly on specific receptors located incircumventricular
organs in the brain (neural organs that lie outside the blood-
brain barrier) to stimulate thirst. The neuronal pathway from the
circumventricular organs to the hypothalamus also uses
angiotensin II as a neurotransmitter.

 Hypertonicity: Small increases of 1-2% of the effective osmotic
pressure of plasma causes shrinkage of osmoreceptors in the
hypothalamus (due to osmosis from the osmoreceptors to the
ECF).
- Shrinkage of the osmoreceptors results in direct mechanical
stimulation of the thirst center because its dendrites which are
attached to the osmoreceptors are stretched by the shrinkage.
 Hypovolemia: The volume of ECF is sensed via volume receptors
located at the low pressure side of the circulation (i.e. the venous
side, at the junction of the right atrium and the vena cava and at the
entry of the pulmonary vein into the left atrium).
- Hypervolemia stretches these receptors which send inhibitory
impulses through the vagus nerve to inhibit thirst. On the other
hand, hypovolemia stimulates thirst through reduction of the
inhibitory discharge from the volume receptors to the thirst center.
 Hypotension: The blood pressure is sensed via baroreceptors
located at the high pressure side of the circulation (i.e. the arterial
side, at the carotid sinus and the aortic sinus which are found at the
bifurcation of the common carotid artery and the aortic arch
respectively).
- Hypertension stretches these receptors which send inhibitory
impulses through the vagus and the glossopharyngeal nerves to
inhibit the thirst center. On the other hand, hypotension stimulates
thirst through reduction of the inhibitory discharge from these
receptors to the thirst center.
Remember that:
 Thirst is one of the symptoms of dehydration and shock

The hormone atrial natriuretic peptide (ANP) inhibits thirst!
ANP is a peptide hormone released by atria in response to
hypervolemia. It inhibits the effect of angiotensin II on thirst to decrease
ECF volume. It also decreases ECF volume through inhibition of
aldosterone action on the kidney, increasing the rate of glomerular
filtration and increasing the rate of sodium excretion in urine (notice
that loss of sodium is followed by loss of water).
Important note: Drinking stimulates mechanoreceptors in the mouth
and pharynx which provide input to the hypothalamus to attenuate the
sensation of thirst. This occurs before any reduction in plasma tonicity;
thus acting as a safeguard against over-ingestion of water.
Control of water loss

- Under normal environmental and physiological conditions, the
amount of water lost by sweating, respiration and through the skin is
almost constant whereas the amount lost by urine is variable. The
minimal volume of urine that can be excreted to eliminate the
metabolic waste products = 0.5 L/day. The maximal volume depends
on water intake.
- For this reason water loss is controlled through regulation of urine
volume. This involves the kidney and the hormones acting on it.
Renal function
- The functional unit of the kidney is the "nephron" which consists of:
glomerulus, for filtration & tubules: for reabsorption and secretion.
- About 180 L of fluid pass through the glomeruli of the kidney each
day. However, only 1.5 L is excreted in urine indicating that the renal
tubules reabsorb more than 99% of the filtered fluid.

Fig 1.10: The nephron
- Reabsorption of water in the renal tubules occurs as follows:

- The PCT: reabsorbs 70% of the filtrate following sodium
reabsorption. The filtrate remains isotonic
- The loop of Henle: water reabsorption occurs in the thin
descending limb without sodium reabsorption. The filtrate becomes
hypertonic; however it becomes hypotonic at the end of the thick
ascending limb because it reabsorbs solutes without water.
- The DCT: relatively impermeable to water. About 5% of the
filtrate may be reabsorbed. The filtrate remains hypotonic.
- The CDs: Completely impermeable to water except at the
presence of ADH (see ADH below).

Hormonal activity
 ADH
- Antidiuretic hormone, also known as vasopressin
- It is a nona-peptide hormone synthesized in the hypothalamus and
stored in the posterior pituitary gland
- It is released in response to the same major stimuli of thirst, through
similar mechanisms:
o Hyperosmolarity (detected by osmoreceptors located at the
hypothalamus. They cause mechanical stimulation of ADH)
o Hypovolemia (results in less stretch of the volume receptors at
the low pressure side of the circulation and therefore less
inhibition of ADH release)
o Hypotension (results in less stretch of the baroreceptors at the
high pressure side of the circulation and therefore less inhibition
of ADH release)
o Angiotensin II (stimulates ADH release, see below)
o Drugs (drugs that stimulate ADH release include barbiturates,
clofibrate, nicotine, acetylcholine and others)
Functions of ADH
- ADH acts on the collecting ducts in the kidney causing water
retention. It facilitates reabsorption of 7-13% of the filtrate
- When ADH level in plasma is high, it also causes vasoconstriction
resulting in elevation of the blood pressure
Abnormalities of ADH:
- Deficiency of ADH causes polyuria and excessive thirst due to
hypovolemia. Urine volume may reach up to 23 L/day. The condition
is known as diabetes insipidus (DI). It may result from a problem in

the hypothalamus (neurogenic DI) or a problem in the renal receptors
for ADH (nephrogenic DI)
- Excessive ADH secretion causes reduction in urine volume,
hypertension and edema due to water retention. The condition is
known as syndrome of inappropriate ADH secretion (SIADH). It is
caused by many problems; these include head trauma, lung tumors,
pneumonia and pancreatitis.
 Aldosterone
- Steroid hormone synthesized in the adrenal cortex
- It is released in response to the following stimuli:
o Hyperkalemia
Directly stimulates aldosterone release from the adrenal cortex.
o High level of ACTH
The adrenocorticotrophic hormone (ACTH) is released by the
anterior pituitary gland to stimulate secretion of cortisol (not
aldosterone) by the adrenal cortex. But, in high levels (due to
endocrine abnormalities) it also stimulates release of aldosterone.
o The renin-angiotensin-aldosterone system
In this system, renin enzyme which is produced by the Juxta-
glomerular apparatus in the kidney results in formation of
angiotensin II. The later stimulates aldosterone secretion from the
adrenal cortex.
The Juxta-glomerular apparatus (JGA) is formed by:
- Cells of the afferent arteriole (juxta-glomerular cells)
- Cells of the DCT (macula densa cells)
- Lacis cells (= extra-glomerular mesangial cells)

Fig 1.11: The juxta-glomerular apparatus (JGA)
- This apparatus (specifically the juxta-glomerular cells) secretes

renin in response to one of the following stimuli;
o Hyponatremia (low [Na])
o Renal ischemia (e.g. due to hypotension or hypovolemia)
o Sympathetic stimulation
- Renin acts on a plasma peptide known as angiotensinogen (14
amino acids) produced by the liver to form angiotensin I (10 aa).
- Angiotensin I is converted to angiotensin II (8 aa) by the action of
angiotensin converting enzyme (ACE).
- This enzyme is produced by the pulmonary endothelial cells. It is
also released to the circulation by lung macrophages.

- Angiotensin II increases ECF volume & pressure because it causes:
1- Vasoconstriction
2- Stimulation of the sympathetic (this stimulates release of
renin and renin forms angiotensin I and then angiotensin II and
the cycle repeats itself in a positive feedback mechanism) 3-
Stimulation of thirst
4- Stimulation of ADH
5- Stimulation of aldosterone
- Aldosterone acts on the DCT and CDs in the kidney to stimulate
retention of sodium and secretion of potassium. Water follows sodium
resulting in increased ECF volume and pressure.
- Unlike excessive ADH secretion, excessive aldosterone secretion
due to adrenal tumors results in hypervolemia and hypertension but it
does not cause edema. The explanation involves ANP as follows:
 Hypervolemia caused by sodium and water retention stimulates
release of ANP from the atria. ANP acts in the kidney to
increase sodium and water excretion. This prevents
development of edema. This phenomenon is known as
“aldosterone escape phenomenon”.
 Atrial natriuretic peptide (ANP)
- A peptide hormone released by atria in response to hypervolemia.
- It reduces ECF volume through the following effects:
o Inhibition of the effect of angiotensin II on thirst
o Inhibition of the effect of aldosterone on the kidney
o Increasing the rate of glomerular filtration
o Increasing excretion of sodium in urine (= natriuresis; notice
that loss of sodium is followed by loss of water).)

1. The percentage of total body water is higher in:

a. females compared to equivalent males
b. old subjects compared to children
c. infants compared to neonates
d. thin subjects compared to obese ones
e. male children compared to female children
2. Using the indicator dilution method, ECF volume is measured by:
a. heavy water
b. RISA
c. inulin
d. heavy water and RISA
e. Evan’s blue dye
3. The volume of distribution of substance A in an average adult male
was found to be 3.5 litres. This substance could be:
a. distributed to all body fluid compartments
b. highly exchangeable between plasma and interstitium
c. tightly bound to plasma proteins
d. rapidly metabolised by cells
e. all the above are correct
4. The ECF differs from the ICF because it contains:
a. less concentration of sodium
b. lower pH
c. higher temperature
d. osmolarity of about 300 mosm/L
e. higher concentration of chloride
5. The interstitial fluid:
a. constitutes about 5% of total body weight in adults
b. temperature is less than that of the plasma
c. osmolarity is determined by Cl- concentration
d. volume can be measured by using inulin and manitol
e. contains slightly higher concentration of Cl- than plasma
6. In a twenty years old man, the following volumes of distribution are
obtained using the indicator dilution method: inulin = 14L and
Evan’s blue dye = 3L; which of the following is not true:
a- intravascular fluid volume is about 3L
b- ECF volume is about 14L
c- ICF volume cannot be calculated from this data
d- ISF volume cannot be calculated from this data
e- blood volume cannot be calculated from this data

7. The osmolarity of plasma is a function of:
a. calcium concentration
b. protein concentration
c. sodium concentration
d. urea concentration
e. glucose concentration
8. The concentration of calcium in the extracellular fluid is about:
a. 10 mg/dL
b. 5 mmol/L
c. 1.5 meq/L
d. 1.0 %
e. 0
9. Filtration of fluid from plasma to interstitium is increased by:
a. increased capillary oncotic pressure
b. increased capillary hydrostatic pressure
c. increased interstitial hydrostatic pressure
d. decreased interstitial oncotic pressure
e. lymphatic obstruction
10. Edema due to high capillary permeability results from:
a. filariasis
b. renal failure
c. burn
d. hepatic failure
e. deep vein thrombosis
11. Gibbs Donnan equilibrium is responsible for:
a. higher concentration of Na+ in ICF than in ECF
b. lower concentration of K+ in plasma than in ISF
c. slightly higher concentration of HCO3- in ISF than in plasma
d. lower concentration of Cl- in intracellular fluid than in plasma
e. higher volume of interstitial fluid than plasma
12. The ECF/ICF volume ratio is highest in:
a- lean males
b- obese males
c- male children
d- female children
e- newborns

CHAPTER 2
EXCITABLE TISSUES
- Nerves and muscles are said to be excitable because they are
capable of generating electrical signals known as action potentials.
- In addition to action potentials, excitable tissues are also
characterized by resting membrane potentials. However, unlike action
potentials, resting membrane potentials are found in almost all cells of
the body.
THE RESTING MEMBRANE POTENTIAL (RMP)

- It is the difference in electrical potential between the interior and the
exterior of cell membranes at rest, with the interior being more
negative relative to the exterior.
- The cell membranes are said to be “polarized”; i.e. negative inside
and positive outside.
Fig 2.1: The polarized cell membrane
- The difference in potential across the cell membrane can be

measured by special devices (e.g. the Cathode Ray Oscilloscope),
using electrodes placed in the two sides of the cell membrane.
Fig 2.2: Measurement of the resting membrane potential

- The magnitude of the RMP differs in different types of cells, for
example:
In a skeletal muscle cell = - 90 mv
In a cardiac muscle cell = - 90 mv
In a nerve cell = - 70 mv
Causes of the RMP:
a- Potassium efflux
b- The Sodium- potassium pump
c- ICF non diffusible anions
a- Potassium efflux
- This is the major cause of RMP.
- The cell membrane is more permeable to potassium than sodium
(because the hydrated atom of potassium is smaller than the hydrated
atom of sodium).
- Therefore potassium diffuses to the outside down its concentration
gradient through potassium leak channels.
Fig 2.3: Potassium efflux
- For each atom of potassium that diffuses to the outside, a negative

charge is generated inside and a positive charge is generated outside
the cell membrane.

- The positive charges outside the cell membrane rebel the potassium
ions, forcing them back to the inside through the leak channels (down
their electrical gradient from the positive side to the negative side).
However, net potassium efflux continues until the chemical gradient
which drives potassium to the outside is equal to the electrical gradient
that drives potassium to the inside (= stage of equilibrium).
b- The Sodium- potassium pump
- An electrogenic pump that pumps 3 sodium ions to outside and 2
potassium ions to inside, thus generating negative charges within the
cell.
Fig 2.4:The sodium potassium pump
- Sodium and potassium ions are transported actively against their

concentration gradients, using energy released by hydrolysis of ATP
(see chapter 1).
c- ICF non diffusible anions
- Presence of non diffusible anions inside the cell (protein and organic
phosphate) contributes to the genesis of RMP by increasing the
number of negative charges inside the cell (= very low contribution).

The equilibrium potential:
- The equilibrium potential (E) for an ion gives an idea about its role in
genesis of the resting membrane potential. Here the ion is placed in a
medium similar to ECF and allowed to pass into or out of the cell to
reach equilibrium, without contribution of other ions. The membrane
potential generated due to difference in concentrations of that ion in
ECF and ICF is called the equilibrium potential. However, it does not
occur normally because of the contribution of other ions.
- The equilibrium potential can be measured by the Nernst equation

as follows:
 for cations: E = 61 log [cation]ECF/[cation]ICF

 for anions E = 61 log [anion]ICF/[anion]ECF
- Examples:
 E for K+ = 61 log 4/140 = - 90 mv (close to the RMP, indicating

a major role of K+ in the genesis of RMP).
 E for Na+ = 61 log 150/15 = + 61 mv (very far from the RMP,
indicating a minor role of Na+ in genesis of the RMP).
 E for Cl- = 61 log 110/8 = - 70 mv (However, there is no
evidence that Cl- has an active transport similar to Na + and K+;
so it does not contribute to the RMP).
- The Goldman equation can be used for direct calculation of the
RMP. It includes the effects of the major ions and their permeabilities
(P) across the cell membrane; as follows:
RMP (mv) = 61 log PK [K]ECF + P Na [Na]ECF + PCl [Cl]ICF
PK [K]ICF + P Na [Na]ICF + PCl [Cl]ECF

THE ACTION POTENTIAL (AP)
- Occurs only in excitable tissues (nerve & muscle).
- Involves alterations in the membrane potential (depolarization and
repolarization) following sufficient mechanical, electrical or chemical
stimulation.
- The action potential can be recorded by special devices (e.g. the
cathode ray oscilloscope).
- The recorded action potential can be: Monophasic in which the

recording electrodes are placed on the surface of cell membrane; or
Biphasic in which they are placed on the two sides of cell membrane.
Components of the action potential
1- Stimulus artifact
- Occurs at the time of stimulation (marks the point of stimulation)
- Due to current leakage from the stimulus electrode
2- Latent period
- The isopotential interval from the point of stimulation to the start of

action potential.
- Can be used for measurement of the conduction velocity (CV) in an

axon. Conduction velocity = (the distance between the stimulating and
recording electrodes) divided by (the latent period).
3- Threshold
- The voltage at which the "fast voltage gated sodium channels"open.

If not reached, action potential never occurs.

- It is usually about 15 mv less than the resting membrane potential
(e.g. -75 mv when the RMP is -90 mv).
4- Depolarization
- Due to sodium influx through the "fast voltage gated sodium

channels".
- The membrane potential moves towards the equilibrium potential for

sodium (+60 mv) but it does not reach it because opening of the
sodium channels is short lived (the channels rapidly become
inactivated and will never open again unless the membrane potential
returns back to the resting level); (see the refractory period below).
5- Repolarization
- Due to potassium efflux through "voltage gated potassium

channels".
- Opening of the "voltage gated potassium channels" is slower than

sodium channels; that’s why potassium efflux occurs after sodium
influx. Opening is also more prolonged than sodium channels and
this explains the occurrence of after-hyperpolarization (see below).
- Additional factors that facilitate repolarization are the inactivation of

the "fast voltage gated sodium channels" and the reversal of the
membrane potential (becomes positive inside); thus limiting further
sodium influx.
6- After- depolarization
- The slower fall in the rate of repolarization.
- occurs when repolarization is 70% completed.

7- After-hyperpolarization
- Slight overshooting in the hyperpolarizing direction, due to excess

potassium efflux through the "voltage gated potassium channels", and
then restoration of the membrane potential to the resting level (due to
the activity of the Na/K pump).
Fig 2.5: The action potential
Characteristics of action potentials

1- All or none law
- Sub threshold stimuli can never generate an action potential
whereas threshold and supra threshold stimuli can generate action
potentials of the same magnitude (i.e. full action potential).
- This indicates that action potentials either occur in a full form or do
not occur at all (i.e. all or none).

2- Refractory period
- Period of time during which a cell membrane is refractory to
excitation, because it is already in a state of excitation. During this
period the "fast voltage gated sodium channels" are inactivated
- The refractory period is divided into:
 Absolute refractory period:
o Action potential can never be generated even with supra-
threshold stimulation.
o Its duration from the firing level to the end of one third of
repolarization.
 Relative refractory period:
o Action potential can not be generated by ordinary stimulation
but it can be generated by supra-threshold stimulation.
o Its duration from the end of absolute refractory period to the
end of repolarization (i.e. to the start of after-depolarization).
Fig 2.6: The refractory period

3- Conduction
- Action potential can be propagated (conducted) through axons of
neurons.
- Conduction is an active, self propagating process that occurs with
no change in amplitude or velocity of the action potential.
- There are two types of conduction:
 Conduction in unmylinated nerves (continuous conduction)
 Conduction in myelinated nerves (saltatory conduction)
(jumping of action potential from a node of Ranvier to
another).
Fig 2.7: Types of electrical conduction

- The velocity of conduction depends on:
 Degree of myelination:
- Faster in thick myelinated > thin myelinated > un-myelinated
 Distance between nodes of Ranvier:
- Faster when the distance is increased
 Diameter of the axon:
- Faster when the diameter is larger
The compound action potential

- The above description of action potential refers to action potential
that’s recorded from a single axon. It differs from an action potential
recorded from a peripheral nerve (which contains many axons).
- The action potential that’s recorded from a peripheral nerve is called
the compound action potential and it is characterized by multiple
peaks.
Fig 2.8: The compound action potential
- It represents algebraic summation of action potentials of many axons

in the nerve. The multiple peaks appear because a peripheral nerve
contains different types of fibers with different sizes, thresholds and
peaks.

Effects of ECF electrolyte disturbances on excitability
Disturbances in sodium ions
- Have little effect on the resting membrane potential (RMP).
- Hyponatremia decreases the amplitude of the action potential.
Disturbances in potassium ions
- Affect the resting membrane potential because potassium efflux is
the main cause of the resting membrane potential.
- Hypokalemia causes hyperpolarization (because it allows more K
efflux and therefore the resting membrane potential gets away from
the threshold; this decreases excitability.
Fig 2.9: Hyperpolarization caused by excessive K efflux
- Mild to moderate hyperkalemia limits potassium efflux and therefore

the RMP is elevated to become closer to the threshold, this increases
excitability. However, severe hyperkalemia elevates the RMP to the
level of the threshold and therefore it inhibits excitability (the cell can
not respond to stimulation since its RMP is not below the threshold;
that’s why hyperkalemia prevents excitation of the heart and stops it
in diastole).

Fig 2.10: Effect of hyperkalemia on the RMP
Disturbances in calcium ions

- Calcium ions guard the sodium leak channels, thus preventing
sodium influx through these channels during the resting state.
- In hypocalcemia sodium ions enter the cells because the leak
channels are not guarded, this elevates the RMP and makes the cells
more excitable (for this reason hypocalcaemia is characterized by
high excitability in neuromuscular junctions resulting in involuntary
contraction of some muscles (= this is known as tetany).
- Hypercalcemia has an opposite effect; it prevents influx of sodium
ions through their leak channels; therefore, it stabilizes cell
membranes and decreases excitability.
- Severe hypercalcemia may interfere with the normal function of
nerves and may result in coma.
- Hypercalcemia increases contractility of cardiac muscle but not
skeletal muscle; that’s because calcium ions in ECF enter cardiac
muscle cells and increase contraction (they do not enter skeletal
muscle cells). Severe hypercalcemia stops the heart in systole.

Action potential of the cardiac muscle
Fig 2.11:
- There are two types of muscle in the heart:

 The cardiac muscle proper: whose AP is characterized by the
plateau phase (due to calcium influx). The plateau prolongs the
refractory period.
 The conductive system: whose AP is characterized by the
prepotential (unstable resting membrane potential, mainly due to
slow potassium efflux).
NERVE
- Nerves are distributed throughout the body to form the nervous
system. The nervous system is subdivided into:
 Central nervous system (CNS = the brain and the spinal cord).
 Peripheral nervous system (PNS = the spinal and cranial nerves).
- Each nerve consists of many nerve cells (neurons).

- A neuron is the main functional cell in the nervous system.
- It consists of:
o Cell body (or soma)
o Dendrites
o Axon
Fig 2.12: The neuron
- There are about 100 billion neurons in the CNS and about 10-50
times this number glial cell (neuroglia).
- - Neuroglia (= non-excitable cells) are 3 types in the CNS:
o Microglia
- Phagocytic cells in the brain (resemble tissue
macrophages)
o Astrocytes (= macrglia)
- Provide a supportive matrix around the neurons
- Form part of the blood brain barrier (BBB)
- Maintain stable ECF concentration of ions (by taking
up K+)
- Two types: fibrous astrocytes (in the white matter) and
protoplasmic astrocytes (in the gray matter)
o Oligodendrocytes (= macroglia)
- Form myelin sheath around axons in the CNS

- There is one type of glia in the peripheral nervous system (PNS):
o Schwann cells
- The only glial cells in the PNS
- Form myelin sheath around axons in the PNS
- Each cell wraps its membrane around axons up to
100 times to form a myelin sheath
Fig 2.13: Myelination
Types of nerve fibers

- Nerve fibers are divided into 3 groups: (A, B and C).
- These groups differ in the axon size and degree of myelination.
- The A group is subdivided into: (A, A, A and A).
Group A
 Thick myelinated = The fastest (especially the A type)
 Has the largest diameter
 Carries touch, proprioception and motor impulses
 Most susceptible to pressure
 Least susceptible to local anesthetics, that’s why touch
sensation, which is carried by type A fibers, is not completely
depressed by local anesthetics

 Conduction velocity of type A fibers:
- A = 70-120 m/s
- A = 30-70 m/s
- A = 15-30 m/s
- A= 12-30 m/s
Group B
 Thin myelinated
 Found in the preganglionic autonomic neurons
 Most susceptible to hypoxia than to pressure or local
anesthetics
 Conduction velocity= 3-15 m/s
Group C
 Un-myelinated
 Mainly carries pain and cold sensations
 Also found in the postganglionic sympathetic neurons
 Most susceptible to local anesthetics (that’s why local
anesthetics depress pain sensation which is carried through
type C fibers)
 Least susceptible to hypoxia and pressure
 Conduction velocity= 0.5-2 m/s
Important note
- There is another method of nerve fiber classification (Ia, Ib, II, III
and IV) However, it is rather confusing.
- Here Ia, Ib, II and III are equivalent to the subdivisions of group A
fibers whereas IV is equivalent to type C fibers.
- This classification is used to describe afferents of the muscle
spindle & the Golgi tendon organ (see the motor system).

SYNAPTIC TRANSMISSION
THE SYNAPSE
- It is a junction between two neurons. It allows transmission of
electrical impulses from one neuron to another.
- The transmission is called "chemical transmission" because a
chemical substance "a neurotransmitter" is released by the first neuron
(the pre-synaptic neuron) to bind receptors in the second one (the post-
synaptic neuron). However, direct electrical transmission can occur
through special synapses.
- Unlike electrical transmission through the axons, chemical
transmission is uni-directional (i.e. allows conduction in one way only;
from the pre-synaptic neuron to the post-synaptic neuron).
- The total number of synapses in the CNS is very large; a single axon
may divide to form over 2000 synaptic endings.
- Most synapses occur between the axon terminals of the pre-
synaptic neuron and the cell body or dendrites of the post-synaptic
neuron (axo-somatic and axo-dendritic connections). However, other
types of connection may occur (e.g. axo-axonal).
Fig 2.14: Synapses

General structure of the synapse
Fig 2.15:
The presynaptic neuron:

 Releases a neurotransmitter (NT) through the presynaptic
membrane
 The NT is synthesized in the cell body, packed into vesicles in
the Golgi apparatus and then transported through the axon to
be stored at the terminal end of the axon.
 The terminal end of the axon is slightly dilated for storage of the
NT. It is called the synaptic knob or button.
The postsynaptic neuron:
- Contains receptors for the NT.
- The receptors are located on the postsynaptic membrane.

The synaptic cleft:
- The area that separates the pre and post synaptic neurons
- It is about 20-40 nm wide
- The NT has to cross this area to bind its receptors on the
postsynaptic membrane
- It may contain an enzyme for hydrolysis of the NT and therefore
terminates its action (e.g. acetylcholine esterase enzyme for
hydrolysis of acetylcholine).
Steps of neurotransmitter release to the synaptic cleft

1- Arrival of the action potential to the terminal end of the axon 2-
Opening of voltage-gated Ca++ channels, allowing Ca++ influx
3- Ca++ stimulates release of the neurotransmitter (NT) from the
vesicles by exocytosis (it increases movement of the vesicles to
fuse with the pre-synaptic membrane and facilitates theprocess
of exocytosis)
4- The NT within the vesicles is released to the synaptic cleft.
- Note: Ca++ is then removed from the knob by "Ca2+/Na+ antiport "
Fate of the neurotransmitter at the synaptic cleft

 Neurotransmitters at the synaptic cleft may:
1- Combine with receptors on the post-synaptic membrane (to
exert their effects)
2- Be hydrolyzed by an enzyme in the synaptic cleft
3- Return back to the synaptic knob by endocytosis
4- Diffuse to the plasma (where it is catabolized there or in other
tissues)

Fig 2.16: Fate of neurotransmitters at the synapse
Notes to remember:
 Not all of these options are applicable for all types of
neurotransmitters.
 For example: acetylcholine is hydrolyzed in the cleft by
acetylcholine-esterase into acetate and choline. Therefore it
does not return back to the synaptic knob by endocytosis;
however, its metabolite choline returns back.
 Another example: noradrenaline is not hydrolyzed in the cleft.
Therefore it returns back to the synaptic knob by endocytosis
and packed again into vesicles to be released later (recycling).
 Because it is not hydrolyzed in the cleft, the amount of
noradrenaline that diffuses to plasma is higher than that of
acetylcholine.

ELECTRICAL EVENTS IN THE POSTSYNAPTIC NEURON
- When a neurotransmitter combines with its specific receptor, it
results in opening or closure of some "ligand gated channels" on the
postsynaptic membrane.
- This changes the permeability of the postsynaptic membrane to
specific ions and results in a postsynaptic potential.
- The postsynaptic potential is a local potential that can be excitatory
or inhibitory (depending on which type of ion channels is opened).
Excitatory post synaptic potential (EPSP):
 This is a depolarizing potential that increases excitability of the
post-synaptic neuron
 It does not cause a response because it does not reach the
threshold
 It is caused by an excitatory neurotransmitter that opens:
- sodium channels causing sodium influx
- or calcium channels causing calcium influx
Inhibitory post synaptic potential (IPSP):
 This is a hyperpolarizing potential that decreases excitability of
the post-synaptic neuron
 It is caused by an inhibitory neurotransmitter that opens
potassium or chloride channels causing potassium efflux or
chloride influx respectively or closes: sodium or calcium
channels preventing their influx.
Summation of local potentials:
- For an EPSP to reach a threshold and cause a response, it should
summate with other EPS potentials.
- There are two types of summation: spatial and temporal.

Spatial summation: Occurs when multiple EPSPs arrive
simultaneously, at the same time, on the post-synaptic neuron. The
potentials when added together reach the threshold and produce an
action potential.
Temporal summation: Occurs when a single synaptic knob is
stimulated repeatedly to produce successive EPSPs. These when
added together reach the threshold and produce an action potential.
Fig 2.17: Summation of local potentials
Action potential in the post-synaptic neuron

- Summation of several EPSPs generates an action potential in the
post-synaptic neuron.
- The action potential starts in the generator zone which is situated
at the origin of the axon (axon hillock).
- It is more excitable than the rest of the axon because:
 It contains higher number of voltage-gated Na+ channels
 Its threshold is more near to the RMP (-59 mV)

Inhibition and facilitation at synapses
Direct inhibition
 Occurs directly by releasing an inhibitory NT from a
presynaptic neuron into a postsynaptic neuron.
 This direct inhibition on the postsynaptic neuron is called
postsynaptic inhibition.
Fig 2.18: Direct inhibition
Indirect inhibition
 Occurs indirectly on the neuron
 Has many forms; for example:
o it follows a previous discharge on the postsynaptic neuron (=
here the already excited postsynaptic cell is in a refractory
period or in after-hyperpolarization (Periods of low excitability)
o it occurs in a postsynaptic neuron if the release of the excitatory
NT coming from its presynaptic neuron is prevented by direct
inhibition from another neuron (this is known as presynaptic
inhibition)

Fig 2.19: Indirect inhibition
Properties of synapses
a- Transmission is uni-directional
- From the presynaptic neuron to the postsynaptic neuron.
b- Synaptic delay
- The minimum time required for chemical conduction from a synaptic
knob to its postsynaptic neuron is a bout 0.5 ms.
- Measurement of synaptic delay within the CNS gives information
about the number of synapses in a pathway. For example if the delay
is about 1.2 ms, the number of synapses is probably two.
c- Synaptic fatigue
- Failure or decrease in frequency of conduction in a synapse
following repetitive stimulation.
- Due to exhaustion of the NT (release of all vesicles at the synaptic
knob) or inactivation of the receptors at the postsynaptic membrane.
d- Post-tetanic facilitation
- Increased frequency of conduction in a synapse following repeated
stimulation.
- Caused by increased availability of calcium in the synaptic knob
due to repeated stimulation.

e- Convergence and divergence
- Most of the inputs to the postsynaptic neurons are multiple
(convergence).
- Most of the outputs from the presynaptic neurons are multiple
(divergence)
Fig 2.20: Convergence and divergence
The Neuromuscular junction (NMJ)

- Special type of synapse (between a neuron and a muscle cell).
- The muscle cell membrane that receives the terminal end of the
neuron is known as the motor end plate. It is characterized by multiple
invaginations (junctional folds) that increase its surface area.
- Transmission through the NMJ is similar to chemical transmission
through other synapses.
- The neurotransmitter is acetylcholine and the receptors are
nicotinic.
- The local potential produced by binding of acetylcholine to its
nicotinic receptors at the NMJ is called the end plate potential.
- The end plate potential is always excitatory (caused by sodium
influx) and it is regularly capable of generating an action potential (the
high amount of acetylcholine released in the cleft is 10 times sufficient
for generation of an action potential).

Fig 2.21: The neuromuscular junction
Factors affecting neuromuscular transmission

 Autoimmune destruction of acetylcholine receptors at the NMJ (=
Myasthenia gravis): characterized by weak skeletal muscles.
 Autoimmune destruction of calcium channels at the synaptic knob
of the NMJ (= Lambert-Eaton syndrome): similar to Myasthenia but
unlike it, the weakness of skeletal muscles is improved by repeated
contractions, due to increased Ca++ level in the knob.
 Blockers of acetylcholine receptors (e.g. curare and
succinylcholine): cause paralysis of skeletal muscles.
 Snake venoms: block acetylcholine receptors causing paralysis.
 Organophosphorus compounds (OPC e.g. parathion) & nerve
agents (e.g. Sarin, Tabun and VX): inhibit acetylcholinesterase to
allow acetylcholine to act for prolonged periods in both nicotinic
receptors (causing fasciculations, tachycardia & mydriasis) and
muscarinic receptors (causing bradycardia, bronchospasm,
salivation, lacrimation, diarrhea and vomiting). OPC are used as
insecticides whereas nerve agents are military weapons.
 Botulinum toxin: released by bacteria (Clostridium botulinum):
Prevents release of acetylcholine from neurons causing paralysis.

MUSCLE
Types of muscle
- There are 3 types of muscle:
 Skeletal muscle
- Striated
- Under voluntary control (somatic nervous system)
- Has no anatomical connection between fibers
- Does not contract in the absence of external stimulation
Fig 2.22:
 Cardiac muscle
- Striated
- Under involuntary control (autonomic nervous system)
- There are connections between fibers (gap junctions and
intercalated discs)
- Contracts rhythmically in the absence of external stimulation
Fig 2.23:

 Smooth muscle
- Non striated
- Under involuntary control (autonomic nervous system)
- Connections between fibers may be present (e.g. smooth
muscle in viscera) or absent (e.g. smooth muscle in the eye).
Fig 2.24:
Structure of skeletal muscle

- Each muscle consists of bundles of fibers
Fig 2.25:
- Each fiber is a single cell, composed of myofibrils

Fig 2.26:

- Each myofibril consists of filaments, the filaments are:
 Thick filaments: myosin II
 Thin filaments: actin, tropomyosin and troponins (I, T & C)
 Others: actinin and titin
Fig 2.27:
Striations
- Appearance of alternate light and dark bands in skeletal or cardiac
muscle fibers when examined under direct polarized light, using the
microscope.
- Are due to differences in refractive indexes of thick & thin filaments
- The light area (I band):
 Is isotropic to polarized light
 contains actin only
 divided into two halves by the Z line
- The dark area (A band):
 is anisotropic to polarized light
 contains myosin + ends of actin
 contains lighter area in the middle (H band) that contains
myosin only and divided by the M line

- The area between two Z lines is called sarcomere
- The sarcomere is the functional unit of muscles. It contains an A
band + two halves of I band.
Fig 2.28:
The thick filaments:

Myosin II
- Each has 2 heavy chains and 4 light chains forming a tail and 2
globular heads.
- Each head of myosin has:
 Actin binding site
 ATPase activity
Fig 2.29:

The thin filaments :
a- Actin:
- Consists of two chains that form double helix
- Has active sites that act as targets for myosin heads
Fig 2.30:
b- Tropomyosin:
- Lie in the groove between the two filaments of actin
- Hides the actin active sites during relaxation of muscle
- This prevents binding of myosin heads to actin
Fig 2.31:

c- Troponins:
- Troponin T: binds other troponin units to tropomyosin
- Troponin I: inhibits interaction between actin and myosin
- Troponin C: binds calcium which initiates contraction
Fig 2.32:
The sarcotubular system

- Membranous structures in the muscle fiber
- Made up of: T tubules & sarcoplasmic reticulum
Fig 2.33:

The T tubules:
- Are transverse tubules that arise as invaginations from the cell
membrane.
- Located at the A-I junctions in skeletal muscles (= two per cell); and
at the Z lines in cardiac muscles (one per cell).
- Inside the cell they are perforated by the myofibrils.
- They transmit action potentials from the sarcolemma to the interior
of the cell.
The sarcoplasmic reticulum:
- Forms irregular curtain around the myofibrils.
- Has an enlarged terminal on each side of the T tubule "the
sarcoplasmic cisternae". These form with the T tubule a triad (Ttubule
+ 2 cisternae on each side).
- It stores calcium to be released to the sarcoplasm when an action
potential arrives through the T tubule.
Molecular basis of contraction (Sliding theory)

- Contraction occurs by sliding of the thin filaments over the thick
filaments, thus shortening the sarcomers.
Steps of muscle contraction:
 Depolarization of the sarcolemma (by an action potential
coming from the neuromuscular junction).
 Transmission of the action potential to interior of the muscle cell
via the T tubules.
 The passage of the depolarization wave through the T tubules
induces opening of dihydropyridine receptors in the membrane
of the T tubules.

 The dihydropyridine receptors:
o in the cardiac muscle they allow influx of calcium & this
triggers release of stored calcium in the terminal cisterns.
o in skeletal muscle fibers they act as sensors that detect
arrival of the depolarizing wave & trigger release of stored
calcium.
 Release of stored calcium from the terminal cisterns to the
sarcoplasm occurs via the ryanodine receptors
 Calcium in the sarcoplasm binds to troponin C
 This results in:
o Weakness of the binding of troponin I to actin
o Conformational changes in tropomyosin
 Tropomyosin moves laterally to uncover the actin active sites
 Myosin heads bind the uncovered actin active sites
 ATP is hydrolyzed and the energy released by hydrolysis
causes flexion of myosin heads inwards.
 This causes sliding of actin on myosin resulting in shortening
of the sarcomers (= contraction).
Fig 2.34:

Notes to remember:
- The process by which depolarization of the muscle cell results in
contraction is known as excitation-contraction coupling.
- Seven active sites in actin are uncovered for each molecule of
troponin C that binds a calcium ion.
- Contraction of skeletal muscle depends on release of stored
calcium from the sarcoplasmic reticulum whereas contraction of
cardiac and smooth muscles requires influx of calcium from the
ECF.
- The calcium binding protein in smooth muscle is known as
calmodulin. Unlike troponin, calmodulin initiates contraction
immediately. First it activates a kinase enzyme that’s needed for
phosphorylation of myosin head. This phosphorylation triggers the
ATPase activity of the head and this is followed by contraction.
Steps of muscle relaxation:
 Shortly after releasing calcium to the sarcoplasm, the
sarcoplasmic reticulum begins to transport it back actively by
the Ca-Mg ATPase pump
 When the level of calcium in the sarcoplasm is lowered
sufficiently, calcium is released from troponin C
 This causes actin & myosin interaction to stop, tropomyosin
returns to its position & the muscle relaxes.
Remember that:
 ATP is consumed for both contraction & relaxation.
 If calcium transport back to the sarcoplasmic cisterns is inhibited,
relaxation will never occur (= contracture)

 If no energy is available for relaxation (no ATP), the muscle
becomes rigid (= rigor). A common example is (rigor mortis) which
occurs after death.
- Relaxation in smooth muscles follows de-phosphorylation of myosin
heads by a phosphatase enzyme. However, contraction may continue
in spite of that for some time; this is due to the latch bridge mechanism.
- In the latch bridge mechanism, myosin remains attached to actin
resulting in a sustained contraction with minimal energy expenditure;
as in the vascular smooth muscle.
Types of contraction
Isotonic contraction:
- Isotonic contraction (the same tension) is contraction against a
constant load that results in shortening of a muscle.
- The muscle develops a constant tension throughout the range of
movement (e.g. when lifting a light object).
Isometric contraction:
- Isometric contraction (the same length) is contraction without
appreciable shortening of a muscle.
- The tension developed by the muscle is not constant, it is increasing
(e.g. when trying to lift a very heavy object).
- Since there is no distance of movement (the same length of muscle);
no work is done during the isometric contraction (remember that work
= force times distance, which is zero).
- Standing involves isometric contraction of muscles whereas walking
involves both isometric & isotonic contractions.

Single muscle twitch and summation of contractions
- A single sufficient stimulation of a muscle fiber results in a single
action potential that results in a single contraction followed by
relaxation (= single muscle twitch).
- The duration of the single muscle twitch is longer than the duration of
the action potential.
- Repeated stimulation of a muscle fiber results in repeated action
potentials that are followed by successive contractions.
- Since there is no refractory period for contractions, each new
contraction starts before completion of the previous one. This results
in summation of these contractions.
- The tension developed by summation of contractions is greater than
that’s developed by a single contraction.
- Summation of contractions into one continuous contraction is called
tetanus.
Tetanus
- Tetanus may be complete (with no any relaxation between
contractions) or incomplete (with some incomplete relaxationsbetween
contractions).
- The frequency of stimulation that results in tetanus is determined by
the duration of the single muscle twitch.
- With a frequency of stimulation just below the frequency of
summation, the tension developed is increased by each new stimulus
until a uniform tension per contraction is reached. This is calledtreppe
or staircase phenomenon.
- Here the increase in tension is not due to summation, it is due to
increased availability of calcium to troponin C.

Types of muscle fibers
There are two types of muscle fibers:
Type one fibers:
 Called red muscles (darker than other types)
 Respond slowly to stimulation (i.e. have long latency)
 Have high oxidative capacity
 Contract to maintain posture
 E.g. muscles of the back
Type two fibers:
 Called white muscles
 Have short twitch duration
 Respond rapidly (i.e. have short latency)
 Have high glycolytic capacity
 Specialized for fine skilled movement
 E.g. muscles of the hand
The oxygen debt mechanism

- During severe exercise, the amount of oxygen delivered to skeletal
muscle by the circulation is not enough for aerobic metabolism; for this
reason skeletal muscle has to find extra oxygen or additional sources
of energy; this is achieved as follows:
 It takes oxygen from myoglobin
 It metabolizes glucose anaerobically to lactic acid to synthesize
ATP
 It uses phosphorylcreatine to synthesize ATP
- Hyperventilation after exercise provides extra amount of oxygen that
can be used to repay oxygen taken from myoglobin, to

catabolize lactic acid to carbon dioxide and water, and to replenish
phosphorylcreatine.
- This extra amount of oxygen consumed after exercise is described
as the oxygen debt.
- The mechanism of oxygen debt does not occur in the cardiac muscle
because it depends exclusively on aerobic metabolism for energy
production.

1- The resting membrane potential is generated by:
a. opening and closure of ligand gated channels
b. passage of ions through voltage gated channels
c. selective permeability of the cell membrane to potassium
d. closure of sodium leak channels by calcium
e. the high concentration of phosphates in the cell
2- The following is true about the action potential:
a. an external stimulus is not always needed for its initiation
b. the depolarization phase is always due to Na+ influx
c. its duration is equal in all types of excitable cells
d. after-depolarization phase is due to activity of the Na+/K+ pump
e. it can be summated in skeletal but not in cardiac muscle
3- Concerning myelination, which of the following is not true:
a. synthesized from phospholipids and protein
b. found in preganglionic sympathetic neurons
c. found in postganglionic sympathetic neurons
d. found in the central nervous system
e. formed by oligodendroglial cells
4- If ECF K+ concentration is increased from 3.5 to 5.0 mmol/L:
a. the resting membrane potential becomes less negative
b. the resting membrane potential will not change
c. fast voltage gated sodium channels will open
d. an action potential will occur spontaneously
e. the cell membrane becomes hyperpolarized
5- Leak channels:
a. are present in almost all cells in the body
b. have gates that open or close during action potentials
c. have gates that open when a hormone binds to its receptor
d. are responsible for the depolarization phase of action potentials
e. gates are closed by the end of the action potential

6- Calcium channels in synaptic knob:
a. Allow release of neurotransmitter through them
b. Are voltage gated
c. Are ligand gated
d. Are opened when acetylecholine is released
e. Cause termination of the action potential
7- These proteins are involved in skeletal muscle contraction except:
a. calmodulin
b. actin
c. tropomyosin
d. myosin
e. troponin C
8- The A band in a striated muscle
a. is a light area
b. contains thick filaments only
c. is divided by the M line
d. is longer during relaxation than during contraction
e. appears due to overlapping between actin and myosin
9- Concerning chemical conduction, which of the following is not
true:
a. it is unidirectional (one way direction)
b. excitatory neurotransmitters open Na+ channels
c. inhibitory neurotransmitters open Ca++ channels
d. GABA opens CI- channels in the postsynaptic neurons
e. the post-synaptic neuron is influenced by many pre-synaptic
neurons
10- Ryanodine receptors:
a. allow influx of calcium from ECF to ICF in cardiac muscle
b. allow release of calcium from the sarcoplasmic cisternae to ICF
in skeletal muscle
c. are found in skeletal but not cardiac muscle
d. act as sensors for arrival of excitation through the T tubule
e. allow pumping back of calcium to sarcoplasmic cisternae
11- Isometric contraction differs from isotonic contraction in that:
a- it does not occur in cardiac muscle
b- it occurs during walking
c- it does not involve interaction between actin and myosin
d- the muscle tension applied is increased during the contraction
e- the force applied equals zero

CHAPTER 3
THE AUTONOMIC NERVOUS SYSTEM
INTRODUCTION
- The nervous system can be classified into two physiological
divisions: The somatic nervous system (SNS) and the autonomic
nervous system (ANS)
Table 3.1: Comparison between the SNS and the ANS:
The somatic nervous system The autonomic nervous system

- Controls voluntary functions - Controls involuntary functions
e.g. limb movements e.g. cardiac beats
- Supplies skeletal muscles - Supplies smooth and cardiac
muscles
- One neuron connects the - Two neurons connect the central
central part with the target part with the target muscle
muscle - The two neurons are:
preganglionic & postganglionic
neurons connected by a ganglion
Fig 3.1 Peripheral neurons of the SNS and the ANS

Divisions of the autonomic nervous system
- The autonomic nervous system (ANS) is divided into:
 Sympathetic division
 Parasympathetic division
Differences between the sympathetic and the parasympathetic
divisions:
* Activators
- Stressful stimuli (e.g. fear, pain, exercise…) activates the
sympathetic while complete physical and mental rest (e.g. sleep)
activates the parasympathetic.
* Metabolism
- The sympathetic nervous system causes catabolism for immediate
release of energy that’s used for fight or flight; whereas the
parasympathetic is associated with anabolic reactions that store
energy until needed by the body.
* Anatomical points
- The peripheral parts of the ANS are made up of preganglionic
(myelinated, type B) and postganglionic (unmyelinated, type C)
neurons.
- The cell bodies of the preganglionic neurons are located in the lateral
horn of the spinal cord or the motor nuclei of the cranialnerves 10, 9,
7 and 3 (= 1973). Their axons pass through the ventral horns to the
spinal nerves and then they follow the blood vessels to the target
organs.
- The preganglionic neurons of the sympathetic are short. They leave
the spinal nerve through white rami communicantes to synapse in
sympathetic ganglia with postganglionic neurons that return back to

the spinal nerve via gray rami communicantes to be distributed to their
targets. They are longer than the preganglionic neurons.
Fig 3.2: Origin and course of a preganglionic neuron
- The sympathetic ganglia, the site of cell bodies of the

postganglionic neurons, are connected together to form the
sympathetic trunk that extends parallel to the thoracic and upper
lumbar spinal segments. Additional sympathetic ganglia are also found
in the neck (superior, middle and stellate ganglia) and in the abdomen
(collateral ganglia).
- On the other hand, the preganglionic parasympathetic neurons are
longer than the postganglionic. The ganglia are found near or within
the wall of the target organs.
Fig 3.3: The output of autonomic neurons

Output from the CNS
- The central parts of the sympathetic and parasympathetic nervous
systems originate from certain autonomic centers at the brain (e.g. the
hypothalamus or the brain stem) and then descend through the spinal
cord.
- The peripheral part of the sympathetic passes out through the spinal
nerves that originate from the thoracic and some lumbar segments
(from T1 to L2); whereas the peripheral part of the parasympathetic
passes out through some cranial nerves (number10, 9, 7 and 3) and
some sacral spinal nerves (S2, S3 and S4).
- For this reason the outflow of the sympathetic is described as
thoraco-lumbar and that of the parasympathetic as cranio-sacral.
* Effects
- The ratio of a preganglionic neuron to postganglionic neurons is
about 1:20 for the sympathetic neurons and 1:1 for the
parasympathetic neurons. This indicates that the effects of the
sympathetic are generalized (because of divergence of its
preganglionic neurons) while those of the parasympathetic are
localized.
* The neurotransmitters released by the neurons
- All preganglionic neurons whether sympathetic or parasympathetic,
and all postganglionic parasympathetic neurons release acetylcholine
whereas most postganglionic sympathetic neurons release
noradrenaline. Others release acetylcholine.
- Postganglionic sympathetic neurons that release acetylcholine
supply the sweat glands, arterioles of skeletal muscles and pilo-
erectror muscles.

Table 3.2: Comparison between the symp. and the parasymp.
Difference Sympathetic Parasympathetic
Activator* Stress Rest
Metabolism* Catabolic to release Anabolic to store
energy for fight or flight energy until needed
Pregan. neurons Short Long
Postga. neurons Long Short
Ganglia Near the spinal cord Near or within the
(paravertebral) wall of the organ
Output from the Thoracolumbar Craniosacral
CNS*
Effects* Generalized Localized
Neurotransmitter Pregananglionic: Preganglionic
released by the = Acetylcholine = Acetylcholine
neurons Postganglionic Postganglionic
= Noradrenaline = Acetylcholine
THE NEUROTRANSMTTERS
- The principal neurotransmitters (NT) in the autonomic nervous
system are acetylcholine and noradrenaline.
Acetylcholine:
- Synthesized from acetyl co A and choline in the cell body of
cholinergic neurons (i.e. neurons that release acetylcholine).
- Synthesis is catalyzed by the enzyme choline acetyltransferase.

- Acetylcholine is released by:
o All preganglionic parasympathetic neurons
o All postganglionic parasympathetic neurons
o All preganglionic sympathetic neurons
o Some postganglionic sympathetic neurons (those
supplying sweat glands, arterioles of skeletal muscles and
pilo-erector muscles)
- When released at the synaptic cleft, acetylcholine acts on its
receptors. However, its action is terminated by the
acetylcholinesterase enzyme which converts it to acetate and
choline. Therefore generally no acetylcholine diffuses to plasma.
Noradrenaline (= norepinephrine):
- Synthesized from the amino acid tyrosine in noradrenergic
neurons (i.e. neurons that release noradrenaline)
- Steps of synthesis:
 Tyrosine (from diet or from phenylalanine) is hydroxylated to
dopa (by tyrosine hydroxylase in the cytoplasm).
 Dopa is decarboxylated to dopamine (by dopa decarboxylase
in the cytoplasm).
 Dopamine is converted to norepinephrine (by dopamine beta
hydroxylase in the vesicles).
- Noradrenaline is also synthesized in the adrenal medulla (an
endocrine gland regarded as a modified sympathetic ganglionthat
lost its postganglionic axons). However, in this gland most of the
synthesized noradrenaline (= norepinephrine) is converted to
adrenaline (= epinephrine) by the enzyme phenylethanolamine-N-
methyltransferase (PNMT).

- Adrenaline, noradrenaline and dopamine are called
catecholamines.
- In summary, noradrenaline is released by:
o Most postganglionic sympathetic neurons (excluding
those which release acetylcholine).
o The adrenal medulla (releases adrenaline plus some
noradrenaline).
- When released at the synaptic cleft, noradrenaline acts on its
receptors. There is no enzyme for its hydrolysis in the cleft.
However, after its diffusion into the plasma, it is hydrolyzed by two
enzymes:
 Monoamine oxidase (MAO)
 Catechol-O-methyl-transferase (COMT)
- The most important metabolite is vanillylmandelic acid (VMA),
which is excreted in urine.
- Excretion of high amount of this metabolite in urine indicateshyper-
production of catecholamines (e.g. by a tumor in the adrenal
medulla (= pheochromocytoma)).
Fig 3.4: Cholinergic and noradrenergic neurons

Other neurotransmitters:
Dopamine: Released by some interneurons in symp. ganglia
GnRH: Released by some preganglionic neurons
Co-transmitters:
(VIP): May be found with acetylcholine
(ATP, Neuropeptide Y): may be found with noradrenaline
AUTONOMIC RECEPTORS
- These are the receptors for the neurotransmitters in the autonomic
nervous system (i.e. receptors for acetylcholine and noradrenaline)
Acetylcholine receptors
1- Nicotinic receptors (N)
- Stimulated by small amount of nicotine (a chemical substance found
in tobacco).
- Found at the following sites:
 Sympathetic ganglia
 Parasympathetic ganglia
 Neuromuscular junction
 Adrenal medulla
 The brain
2- Muscarinic receptors (M)
- Stimulated by small amount of muscarine (a chemical substance
excreted in urine of tadpoles).
- Found at the following sites:
 All organs supplied by postganglionic cholinergic nerves (these
include all organs in the body supplied by autonomic neurons
except ventricles of the heart and blood vessels of

the skin, abdominal viscera and the kidney which are supplied
only by sympathetic, without parasympathetic supply).
 The brain
Noradrenaline receptors
1- Alpha receptors
Sites of alpha receptors:
Alpha 1:
Blood vessels
Dilator pupillae muscle
Sphincters
Alpha 2:
Pancreas
Presynaptic membranes
2- Beta receptors
Sites of beta receptors:
Beta 1:
The heart
Renin secreting cells
Adipose tissue
Beta 2:
Bronchi
Uterus
Pancreas
Beta 3:
Adipose tissue
-

Remember that:
 Both noradrenaline and adrenaline act on α and β receptors.
 Noradrenaline acts better on α receptors than on β receptors
while adrenaline acts better on β receptors than on α receptors.
Fig 2.5: Autonomic receptors
 N = Nicotinic receptors M= Muscarinic receptors
EFFECTS OF SYMP. AND PARASYMP. STIMULATION

- All postganglionic parasympathetic neurons are cholinergic and
most postganglionic sympathetic neurons are noradrenergic.
- Therefore sympathetic effects are generally mediated by
noradrenaline and parasympathetic effects are generally mediated by
acetylcholine.

- Examples of these effects on various organs in the body:
Organ Sympathetic effect Parasympathetic effect
Eye pupil Dilation (it contracts the Constriction (it contracts
dilator pupillae muscle/ the constrictor pupillae
alpha receptors) muscle/ muscarinic Rs)
Salivary Stimulates secretion Stimulates secretion
glands (small amount, mucus in (large amount, watery in
consistency) consistency)
Bronchioles Bronchodilation/ Bronchoconstriction/
through beta 2 Rs through muscarinic Rs
Heart rate Increased (Positive Decreased (Negative
chronotropic)/ beta 1 chronotropic/ Muscarin.
Contractility Increased No direct effect on
of the heart Positive inotropic contractility (it does not
supply the ventricles)
GIT motility Decreased (inhibitory, Increased (excitatory, it
& contracts the sphincters relaxes the sphincters
Secretions and relaxes the walls) and contracts the walls)
Blood - Vasoconstriction - Does not supply and
vessels (mediated through alpha therefore has no effect
receptors) on blood vessels of the
- Vasodilatation of some skin, abdominal viscera
blood vessels like the and the kidney.
coronary artery - Causes vasodilatation
(mediated through beta 2 in some blood vessels
receptors). like the coronary artery)

Organ Sympathetic effect Parasympathetic effect
Micturition & Not involved in the Excitatory (contracts the

Defecation reflex; but, its walls of the bladder &
reflexes stimulation inhibits rectum & relaxes their
these reflexes sphincters)
Sex organs Mediates the ediates the erection reflex
ejaculation reflex
Sweat glands Causes sweating No effect (does not
supply sweat glands)
BLOCKERS
- Block the actions of neurotransmitters at their receptors
- Two types:
 Competitive blockers
- Compete with the neurotransmitter (NT) for binding with its
receptors.
- The affinity of the receptor for the blocker is higher than for the
NT.
- The blocker occupies the receptor without producing any
response.
 Depolarizing blockers
- Causes prolonged depolarization of the receptor.
- The receptor becomes in state of refractory period, therefore it
does not respond to the neurotransmitter.

Blockers of Acetylcholine
 Nicotinic blockers:
- Blockers of acetylcholine at nicotinic receptors
- Competitive blockers:
o Curare (at the neuromuscular junction)
o Hexamethonium (at the ganglia)
- Depolarizing blocker:
o Large amount of nicotine
 Muscarinic blockers:
 Competitive blockers:
o Atropine
o Scopolamine (hyoscine)
 Depolarizing blocker:
o Large amount of muscarine
Blockers of noradrenaline
 Alpha blockers:
o Phentolamine
o Prazosin (alpha 1)
o Yohimbine (Alpha 2)
 Beta blockers:
o Propranolol
- (non selective blocker; blocks beta 1 & beta 2 receptors)
o Atenolol
- (selective blocker; blocks beta 1)
o Butoxamine
- (selective blocker; blocks beta 2)

ABNORMALITIES
 Horner’s Syndrome
- Results from damage to sympathetic neurons that supply the face
- The damage may occur at any site along the course of sympathetic
neurons which originate from the hypothalamus, descend through the
brain stem, emerge from the upper thoracic segments, synapse at
the superior, middle or inferior cervical ganglia and then pass with
blood vessels to supply the face. However, the damage usually occurs
at the neck (cervical sympathectomy).
- Examples of the causes:
o Apical lung tumor
o Surgical trauma at the neck
o Hypothalamic lesions
- The syndrome is characterized by the following signs (on the
affected side of the face):
o Ptosis (drooping of the upper eye lid)
o Meiosis (constriction of the eye pupil)
o Anhydrosis (dryness, due to loss of sweating)
o Enophthalmos (abnormal recession of the eyeball in the
orbit)
o Rubor (redness, due to vasodilatation)
o Calor (hotness, due to vasodilatation)
 Myasthenia Gravis
- Results from damage to acetylcholine receptors at the
neuromuscular junctions.
- The damage is caused by auto-antibodies induced by unknown
mechanism

- Develops in females more than males.
- It is characterized by:
o Muscle weakness (especially after repeated movement)
o Ptosis (drooping of the upper eye lid)
o Weakness of respiratory muscles (the patient may die
due to respiratory failure).
- Treatment:
- By anti- acetylcholine esterase (e.g. neostigmine); to decrease
break down of acetylcholine at the neuromuscular junction and allow
it to act on the remaining receptors.
- Other modalities of treatment include:
o Use of steroids to inhibit production of the auto-antibodies by
lymphocytes
o Decrease of further breakdown of acetylcholine receptors by
plasmapheresis (a machine that eliminates the autoantibodies
from plasma).
Table 3.3: Effects of drugs acting on autonomic receptors
ATROPINE PROPRANOLOL SALBUTAMOL
Mechanism of Muscarinic β1 & β2 blocker β2 agonist
action blocker (antagonist) (stimulant)
Effects Heart rate Heart rate & - Bronchodilation
GIT motility & contractility Heart rate (side-
secretion Cardiac output effect, because
- Bronchodilation Blood pressure although it is β2
- Dilatation of the - Vasoconstriction agonist, it may
eye pupil - Broncho- react with β1
- Dries mouth constriction receptors resulting
( saliva) in tachycardia)

1. The somatic nervous system differs from the autonomic nervous

system because:
a- it has sensory and motor neurons
b- its neurons release acetylcholine
c- some of its neurons arise from the spinal cord
d- it has nicotinic receptors
e- it causes skeletal muscle contraction
2. Effects of the parasympathetic nervous system include all the
following except:
a- meiosis
b- penile erection
c- increased gastrointestinal motility
d- decreased airway resistance
e- bradycardia
3. Stimulation of the sympathetic nervous system results in:
a- bradycardia
b- recruitment in the cardiac muscle
c- dilatation of skeletal muscle arterioles
d- excessive salivary secretion
e- negative inotropic effect
4. Acetylcholine:
a- is released by all postganglionic sympathetic neurons
b- is released from the adrenal medulla
c- causes contraction of skeletal muscles
d- is blocked by propranolol
e- has alpha and beta receptors
5. The drug that blocks muscarinic receptors results in:
a- tachycardia
b- excessive salivation
c- elevation of blood pressure
d- micturition
e- sweating
6. Nicotinic receptors are found in:
a- arterioles of skeletal muscle
b- motor end plates of skeletal muscles
c- sweat glands in the skin
d- small intestine
e- ventricles of the heart

7. The nicotinic cholinergic receptors at the autonomic ganglia are:
a- blocked by curare
b- stimulated by salbutamol
c- stimulated with noradrenaline
d- blocked by hexamethonium
e- identical to those in skeletal muscles
8. Stimulation of beta 1 receptors results in all the following except:
a- breakdown of adipose tissue
b- increased cardiac output
c- release of renin from the juxta-glomerular cells
d- tachycardia
e- vasoconstriction
9. Adrenal medullary cells are stimulated by:
a- dopamine
b- GABA
c- adrenaline
d- acetylcholine
e- nor-adrenaline
10. Dopamine is:
a- released by all autonomic ganglia
b- an excitatory neurotransmitter
c- an acetylcholine derivative
d- a noradrenaline precursor
e- the main neurotransmitter released by the adrenal medulla
11. Sympathetic nerves
a- release noradrenalin from pre-ganglionic fibres
b- release adrenalin from postganglionic fibres
c- are stimulated during sleep
d- release of acetylcholine by some postganglionic fibres
e- are mostly myelinated
12. Stimulation of the sympathetic nervous system results in:
a- tachycardia through β2 receptors
b- constriction of skin blood vessels through β1
c- dilatation of the eye pupil through β1 receptors
d- contraction of intestinal wall through alpha receptors
e- sweating through muscarinic receptors

CHAPTER 4
TEMPERATURE AND METABOLIC RATE
TEMPERATURE
Normal body temperature
- The temperature of the internal structures of the body is called the
core body temperature.
- It equals 37oC (± 0.5oC) or 98.6oF (± 1.3oF)
- The core body temperature differs from the temperature of the skin
because:
 The temperature of the skin is affected directly by the temperature
of the external environment.
 The subcutaneous fat layer beneath the skin acts as insulator. It
preserves the core body temperature and prevents the effect of the
external environment.
Remember that:
 Skin vasodilatation (as occurs when the core body temperature
rises) allows blood to pass through the subcutaneous fat layer and
comes under the skin to facilitate heat loss to the outside. The
opposite occurs when the core body temperature falls.
Measurement of the core body temperature

- The device used is the clinical thermometer
- The sites used for measurement are:
The rectum
 The most accurate site
 Not socially acceptable
 Used in children and unconscious patients

The mouth (under the tongue)
 The most frequently used site (Socially acceptable)
 Differs slightly from the core body temperature (less by 0.5oC )
 Affected by hyperventilation, smoking and recently ingested food
or drink.
Other less frequently used sites:
o The axilla (less accurate; affected by the external environment)
o The ear (less accurate; affected by the external environment)
o Freshly passed urine (more accurate “but used for research
purposes only”)
Regulation of body temperature

- Maintenance of normal body temperature is an important goal in
homeostasis.
- This is because disturbance in body temperature affects:
 Activity of enzymes
 Speed of metabolic reactions within the body
 Activity of the various systems in the body. For example:
o The nervous system: higher body temperature increases
conduction in neurons whereas lower body temperature
decreases conduction.
o The cardiovascular system: higher body temperature causes
tachycardia and increases contractility whereas lower body
temperature does the reverse.
o The respiratory system: higher body temperature causes
hyperventilation whereas lower body temperature causes
hypoventilation.

o The endocrine system: higher body temperature decreases
release of thyroid hormones whereas lower body temperature
increases release of thyroid hormones.
- Regulation of body temperature within narrow limits is not only a
characteristic of humans; it is also a characteristic of birds and
mammals. For this reason they are described as "warm blooded" or
homeothermic.
- Other vertebrates like reptiles, amphibia and fish are "cold blooded"
or poikilothermic because the range of their body temperature is rather
wide.
- Invertebrates, on the other hand, can not regulate their body
temperature.
The temperature regulatory center:
- There is a center specialized for control of body temperature located
in the hypothalamus, known as the temperature regulatory center.
- This center controls heat loss & heat gain (the anterior
hypothalamus controls heat loss & the posterior hypothalamus controls
heat gain.
- Notice that: to maintain constant body temperature, the degree of
heat loss should always be balanced by an equivalent degree of heat
gain.
Heat loss:
- Heat is lost from the body by:
1. Conduction
- Transfer of heat between objects in contact with each other (From
an object with higher temperature to another with lower
temperature).

- Conduction occurs for either heat loss or heat gain, depending
on the level of body temperature.
2- Convection
- Transfer of heat away from a surface by successive currents of
air or water (from the object to the air or water currents, if they
have temperature lower than that of the object).
- Convection occurs for either heat loss or heat gain, depending
on the level of body temperature.
3- Radiation
- Transfer of heat between objects not in contact with eachother
(from that of higher temperature to another with lower
temperature).
- Radiation occurs for either heat loss or heat gain, depending
on the level of body temperature, compared to the
temperature of the water or air currents.
4- Evaporation
- Vaporization of water molecules from a surface, taking heat.
- For example, evaporation of sweat from the surface of the body
or evaporation of water from the mucus membranes during
respiration.
- Notice that vaporization of 1g of water removes about 0.6 kcal
of heat.
- During exercise, sweat secretion may reach 1.6 L/h.
Evaporation of this volume results in loss of more than 900
kcal of heat per hour.
- Evaporation occurs for heat loss only (heat is always lost, not
gained by evaporation).

Heat gain
- The body gains heat by:
1- Metabolism
- Metabolism of all types of energy substrate, especially brown fat,
produces considerable heat.
- Brown fat is more abundant in infants than adults. It is found
mainly between scapulae and at the nape of the neck. Unlike the
white fat, it has rich sympathetic innervation and high metabolic
activity.
2- Muscular activity
- Contraction of muscles is a major source of heat. This may be
induced voluntarily (e.g. exercise) or involuntarily (e.g. shivering)
- Shivering is stimulated when the body temperature reaches
35.5oC.
3- Food intake (Specific dynamic action of food)
- Obligatory energy release that occurs during assimilation of food
within the digestive system (i.e. before absorption).
- The energy release of specific dynamic action of food is highest
for proteins than for carbohydrates or fats.
4- From the environment
- By conduction, convection or radiation (notice that these
mechanisms are suitable for both heat loss and heat gain).
- Remember that: In a hot weather, the mechanisms of conduction,
convection and radiation are all for heat gain; the only way for heat
loss is through evaporation of sweating. However, in a very humid
environment sweating occurs without evaporation. Therefore the
temperature of the body is not decreased.

Body responses to a hot environment
- Due to the direct effect of a hot environment, the temperature of the
body starts to rise.
- This rise is detected by thermoreceptors located peripherally in
the skin and centrally in the spinal cord and hypothalamus.
- The peripheral and central chemoreceptors send their impulses to
the temperature regulatory center in the hypothalamus.
- The center, to correct the body temperature, increases heat loss
(by the anterior hypothalamus) & decreases heat gain (by the
posterior hypothalamus).
- Heat loss is increased by:
o Sweating (to increase evaporation from the skin)
o Vasodilatation (to increase blood supply to the skin, for
radiation)
o Increased respiration (to increase evaporation from the mucus
membranes).
o Behavioral changes to increase heat loss, these include:
 Stretching at sleep (to increase surface area for radiation)
 Light clothes and cold drinks
- Heat gain is decreased by:
o Decreased metabolism, decreased food intake and decreased
muscular activity.
 Body responses to a cold environment

- Due to the direct effect of the cold environment, the temperature
of the body starts to drop.
- This drop is detected by peripheral and central thermoreceptors.

- The thermoreceptors send impulses to activate the temperature
regulatory center in the hypothalamus.
- The center increases heat gain (by the posterior hypothalamus) &
decreases heat loss (by the anterior hypothalamus).
- Heat gain is increased by:
o Increased metabolism
o Increased food intake (the body temperature rises due to the
specific dynamic action of food).
o Increased muscular activity (shivering and exercise)
- Heat loss is decreased by:
o Decreased sweating (to decrease evaporation from the skin)
o Vasoconstriction (to decrease blood flow to the skin)
o Decreased respiration (to decrease evaporation through the
mucus membranes)
o Behavioral changes that include:
 Curling up at sleep (to reduce the surface area). Other
behavior changes like heavy, dark-colored clothes and
hot drinks increase heat gain.
Physiological variation in body temperature

- Body temperature varies physiologically according to:
Age
- Higher in neonates> children > adults
- The higher temperature in neonates and children is due to heat
released by metabolic reactions of the growing tissues
Gender
- Higher in males than females of the same age and weight

- Due to presence of higher percentage of inactive tissues (fats) in
females
At and following ovulation
- Due to release of progesterone which has thermogenic effect
Pregnancy
- Due to higher rate of metabolism (fetal tissues) & higher level of
progesterone
Lactation
- Due to higher rate of metabolism (breast tissue)
Circulating hormones
- Normal variation in levels of thyroid hormones and catecholamines
results in equivalent variation in body temperature
Circadian fluctuation
- Body temperature fluctuates normally throughout the day of 0.5- 0.7
o
C. It is lowest early in the morning and highest at the evening.
Emotions
- Due to unconscious tensing of muscles.
Sleep and exercise
- Body temperature rises with muscular activity and drops at sleep.
Abnormalities of temperature regulation

Fever (Pyrexia)
 An important sign of disease (e.g. tonsillitis, pneumonia, typhoid,
malaria, malignancies …)
 Caused by endogenous pyrogens (e.g. cytokines released by
phagocytic cells, such as interleukin-1 (IL-1), IL-6 and tumor
necrosis factor (TNF ), which act to increase body temperature).

 Release of the endogenous pyrogens is induced, in most times, by
exogenous pyrogens (substances not synthesized by the bodysuch
as bacterial toxins).
 Interleukins, which can not cross the blood brain barrier to reach the
preoptic area in the hypothalamus, induce synthesis of a substance
(most probably prostaglandin E2) to reach that area which is the site
of temperature setting in the body (= Thermostat).
 Prostaglandin E2 resets the thermostat from 37oC to a higher
level (e.g. 40oC). The subject feels cold, and therefore he
develops changes that elevate the body temperature such as
shivering, non-shivering thermogenesis (breakdown of brown
fat) and skin vasoconstriction; these result in fever.
Remember that:
 Immediately following loss of the prostaglandin effect, the
temperature setting point returns back to 37 oC. Since the body
temperature is still higher than 37oC, the subject develops changes
to decrease the body temperature such as sweating and
vasodilatation of skin blood vessels.
 Drugs that decrease synthesis of prostaglandins can treat fever
(e.g. Aspirin).
Heat stroke
 In a hot dry environment, the only way to lose heat is through
evaporation of sweating.
 Therefore, failure of sweating results in abnormal elevation of body
temperature to a degree that affects the activity of the nervous
system, resulting in convulsions, coma and even death.

 In heat stroke, there is damage to the temperature regulatorycenter
caused by the high environmental temperature. This was confirmed
at autopsy. However, the exact mechanism of damage is not well
understood.
 Sometimes, as in severe exercise, heat stroke may result from
failure of the temperature regulatory mechanisms to maintain
normal body temperature (i.e. inadequate sweating); due to high
rate of heat production by the exercising muscles.
 Failure to reduce body temperature is followed by complications of
high temperature (convulsions, coma and death).
 Treatment should start immediately (e.g. electrical beds to reduce
the body temperature gradually or if not available: ice water;
However, body temperature should not be lowered quickly).
Heat exhaustion
 In a hot humid environment, even sweating can not reduce body
temperature because it fails to evaporate. For this reason subjects
should keep themselves in a cold and well ventilated area to lose
heat.
 In heat exhaustion, there is excessive sweating but with no
evaporation.
 The body temperature becomes elevated, the activity of the nervous
system is affected and the patient develops dehydration (due to the
excessive sweating).
 If not treated, the temperature regulatory mechanisms eventually
fail and the heat exhaustion becomes complicated by heat stroke
(permanent damage to temperature center).

 Therefore it is important to treat the condition immediately by taking
the patient to a well ventilated, cold room and giving him IV fluids
(in form of normal saline).
Table 4.1: Differences between heat stroke and heat exhaustion

Difference Heat stroke Heat exhaustion
Classical environment Hot dry Hot humid
Temperature center Abnormal Normal
Sweating Absent Excessive
Skin Hot & dry Hot & wet
Dehydration Absent Present
Effects of the high temperature
Tachycardia Present Present
Hyperventilation
Convulsions & coma
Hypothermia
 Diagnosed when rectal temperature is < 35oC.
 Characterized by loss of consciousness, bradycardia and
decreased respiration.
 Occurs due to the direct effect of cold environments on slim subjects
with thin subcutaneous fat layer (e.g. malnourished children and old
people); or subjects with immature temperature regulatory
mechanisms (e.g. pre-term babies).
 Treatment by stepwise elevation of body temperature using heavy
clothes or electric blankets (because sudden elevation of body
temperature is dangerous).

Lesions of the hypothalamus
- The anterior hypothalamus controls heat loss (e.g. vasodilatation
and sweating) whereas the posterior hypothalamus controls heat
gain (e.g. shivering).
- Damage involving the anterior hypothalamus causes hyperthermia
in hot environments (due to failure of heat loss) whereas damage
involving the posterior hypothalamus causes hypothermia in cold
environments (due to failure of heat gain).
Malignant hyperthermia
- This is a life threatening condition that occurs due to a mutation in the
gene coding for the ryanodine receptors in skeletal muscles.
- Anesthetic drugs such as halothane and suxamethonium trigger
excessive release of calcium through these receptors from the
sarcoplasmic cisternae into the sarcoplasm, causing prolonged
contraction. Calcium causes contraction of muscles, this results in
sudden rise in body temperature and eventually death.
Heat cramps
- These are brief, painful muscle spasms occurring in the abdomen,
thigh or calf muscles.
- They occur during or after exercise, especially in the un-acclimatized
subjects, due to loss of large amounts of water and salts in sweat.
- Acclimatization involves elevation of aldosterone level which
reabsorbs sodium from sweat glands to prevent its loss in sweat.
- Treatment measures include resting of the muscles, rehydration and
correction of sodium and potassium loss.

THE METABOLIC RATE
- The word metabolism refers to all chemical transformations that
occur within the body.
- It includes:
 Anabolic reactions:
o Synthesis of complex molecules from simpler ones
o Example: glycogen from glucose, protein from amino acids…
o Involves consumption of energy for synthesis
 Catabolic reactions:
o Degradation of complex molecules to simpler ones
o Example: glycogen to glucose, protein to amino acids…
o Involves release of energy during degradation
THE BASAL METABOLIC RATE

 The metabolic rate is defined as the rate of energy release per unit
time.
 If it is measured at certain standard conditions; it is called the
basal metabolic rate (BMR).
 The standard conditions for its measurement are:
o Complete physical and mental rest
o Fasting for at least 12 hours
o Comfortable temperature
 The energy released by the body at these standard conditions is
used to maintain basal functions in the body such as:
o Beating of the heart
o Respiration

o Activity of the nervous system
o Sodium-Potassium ATPase pump
Measurement of the BMR

 Normal BMR = 2000 kcal/day or 40 kcal/m2/h
 Measurement of the BMR was formerly used to diagnose thyroid
problems:
o If increased by 15% = it indicates hyperthyroidism
o If decreased by 15% = it indicates hypothyroidism
BMR is measured by 2 methods:
 Direct Calorimetry
(Not preferred because it is difficult and needs special laboratories)
 Indirect Calorimetry
(Preferred)
Direct Calorimetry
 Involves incubation of a subject in a vessel container for a certain
period of time.
 The vessel container is surrounded by a known volume of water
and covered from outside by insulator.
 The energy released during this period of time, in the form of heat,
will raise the temperature of the water around the container.
 This change in temperature is used to calculate the BMR.
Indirect Calorimetry
 Involves indirect measurement of the BMR by measuring certain
substances consumed or produced during the catabolic reactions.
 For example, take the reaction:

C6 H12 O6 + (6) O2 = (6) CO2 + (6) H2 O + energy (heat)
 Here the amount of energy released is known
 Using the above information, the metabolic rate can be calculated
indirectly by measuring any of the following during a certain period
of time:
o the amount of oxygen consumption
o the amount of glucose consumption
o the amount of carbon dioxide production
o the amount of water production
Using the oxygen consumption:

 The amount of energy produced when one liter of oxygen is
consumed is called the joule equivalent (JE)
 It differs according to difference in the foodstuff being oxidized. This
is because the ratio of carbon to oxygen atoms differs in different
types of foodstuff.
 The difference in the ratio of carbon to oxygen atoms also results
in difference in the respiratory quotients (RQ) of foodstuffs.
 The RQ of each foodstuff is defined as the ratio of carbon dioxide
produced to oxygen consumed in the steady state, when
equilibrium is reached at rest.
 It differs from the respiratory exchange ratio (R) which is the ratio
of CO2 to O2 at any given time (see below).
 The RQ for;
o CHO = 1, Protein = 0.82, Fat = 0.7, Mixed diet = 0.85
 The RQ can be used to calculate the joule equivalent (JE) for each
foodstuff as follows: JE = 17.15 + (RQ x 3.5)

 Now the BMR can be calculated as follows:
 BMR = oxygen consumption x joule equivalent
(in joule/unit time)
 BMR = oxygen consumption x joule equivalent/surface area x 4.2
(in kcal/m2 /h).
Note: The volume of oxygen consumption should be corrected for

standard temperature & pressure (STP) by multiplying it by a factor,
obtained from nomograms (e.g. the correction factor at STP when air
temperature = 21◦c & ambient pressure = 741 mmHg equals 0.883)
Notes to remember about the respiratory exchange ratio (R)
 It is affected by hyperventilation (e.g. during exercise or metabolic
acidosis); here R is increased (due to expiration of more CO 2 by the
hyperventilation). Then following exercise, R is decreased (due to
the oxygen debt mechanism).
 The respiratory quotient (RQ) and the respiratory exchange ratio
(R) of individual organs give information about their activities.
 For example the RQ for the brain (measured during the steady
state) = 0.99; indicating that its main source of energy is glucose.
 The R for the stomach (measured during active secretion of HCl)
is negative, indicating that more CO2 is consumed than produced;
this is used in synthesis of HCL (see the GIT in volume 2).
Measurement of oxygen consumption

 Requirement
 Bell-type spirometer (Benedict’s Roth)
 Kymograph

 Method
 The subject puts the mouth piece of the spirometer in his mouth
 Firstly, the spirometer is connected to the atmosphere to familiarize
the subject to the procedure before recording
 Then the atmospheric opening is closed to allow the subject to
consume the oxygen inside the cylinder of the spirometer
 Oxygen consumption is obtained from a recording on a kymograph
paper of a spirometer by measuring the slope of the line A-B as in
this example:
Fig 4.1: Measurement of oxygen consumption
 Calculation
 BMR = oxygen consumption x correction factor for STP x Joule
equivalent/ Surface area x 4.2

Remember that:
 If the standard conditions mentioned above are not fulfilled; the
value obtained is a metabolic rate (not BMR)
 To calculate the joule equivalent using the formula (JE = 71.15 +
(3.5 x RQ)), the type of foodstuff consumed by the subject over the
past few days should be known; this gives the RQ
 The surface area can be obtained, using the height and weight of
a subject, from nomograms or certain equations
Factors affecting the metabolic rate

 Age
- Higher in neonates> children > adults> old subjects
- Due to increased metabolism of the growing tissues. Here the
metabolic rate should be expressed per surface area for comparison.
 Gender
- Higher in males than females of the same age and weight.
- Due to presence of higher percentage of fats in females.
 At and following ovulation
- Due to the higher body temperature caused by progesterone.
 Pregnancy and lactation
- Due to presence of more metabolically active tissues (fetal and
breast tissues); & higher level of progesterone.
 Circulating hormones
- Normal variation in levels of thyroid hormones and catecholamines
results in equivalent variation in the metabolic rate.
 Emotions
- Due to unconscious tensing of muscles.

 Sleep and exercise
- The metabolic rate rises with activity.
 Recent ingestion of food (SDA)
- Due to the specific dynamic action of food (SDA). As mentioned
earlier it is the obligatory energy release following ingestion of food,
due to its assimilation within the GIT. However, its exact cause is
unknown. It lasts for 6 hours. The rise in metabolic rate is highest
following protein ingestion and lowest following fat ingestion.
 Body temperature and environmental temperature
- The relation between environmental temperature and the rate of
metabolism is generally an inverse relationship (increased
environmental temperature = decreased metabolic rate). However, the
relation between body temperature and the rate of metabolism isa
direct relationship (increased body temperature = increased metabolic
rate).
- The relation between the environmental temperature and the rate of
metabolism is explained by the body responses to hot or cold
environment. - For example, the rate of metabolism rises in a cold
environment and drops in a hot one (see above).
- However, when the environmental temperature rises enough to
elevate the body temperature or drops enough to decrease the body
temperature, the metabolic rate increases or decreases respectively
(i.e. the relation becomes a direct relationship).
- It is calculated that for each one Celsius degree rise in body
temperature, the metabolic rate increases by 14%.

1. The most accurate site for measurement of body temperature is:
a. The mouth
b. The axilla
c. The rectum
d. The nose
e. The skin
2. Whenever the body temperature is lower than the set point of the
thermostat in the hypothalamus:
a. Sweating is increased
b. Skin blood vessels dilate
c. Rate of metabolism is increased
d. Subjects feel hot sensation
e. Appetite to food is inhibited
3. Features of heat stroke include all the following except:
a. Hypotension
b. Dehydration
c. Low urine output
d. Absence of sweating
e. Convulsions
4. Heat exhaustion:
a. Occurs in hot dry environments
b. Is due to failure of sweating
c. Is best treated with ice water immersion
d. Is associated with low plasma osmolarity
e. Is associated with dehydration
5. At the onset of fever, patients develop:
a. Hot sensation
b. Sweating
c. Convulsions
d. Skin vasoconstriction
e. Nausea and vomiting
6. Exposure to a cold environment is not excepted to cause:
a. Release of thyroid hormones
b. Peripheral cyanosis
c. Acceleration of metabolism
d. Reduction in blood pressure
e. Reduction in heart rate
7. The main way for heat loss from a body in a hot dry environment is
through:
a. Sweating
b. Hyperventilation
c. Evaporation

d. Radiation
e. Conduction
8. Concerning regulation of body temperature:
a. Birds and mammals are poikilothermic
b. The temperature regulatory centre is located in the medulla
c. Convection never causes heat gain
d. Shivering occurs when body temperature falls below 36.5 ◦C
e. Damage to the posterior hypothalamus is expected to cause
hypothermia
9. Heat stroke differs from heat exhaustion because it:
a. Usually occurs in both dry and humid environments
b. Is associated with elevated core body temperature
c. Causes tachycardia and impaired level of consciousness
d. Is not characterized by dehydration
e. Is not associated with sweating
10. Measurement of the basal metabolic rate requires:
a. fasting for two hours
b. ingestion of a heavy meal
c. moderate exercise during measurement
d. normal body temperature
e. suitable environmental temperature
11. Basal metabolism is mainly accounted for by:
a. Energy spent by cardio-respiratory functions
b. Secretions in the endocrine system
c. The sodium-potassium pump
d. Maintenance of body temperature
e. Renal tubular mechanisms
12. In the body the metabolism of 10 grams of protein would produce
approximately:
a. 10 kcal
b. 53 kcal
c. 41 kcal
d. 90 kcal
e. 20 cal
13. For measurement of the basal metabolic rate all the following
conditions are required except:
a. mental rest
b. physic rest
c. normal body temperature
d. 12 hours fasting prior to measurement
e. comfortable room temperature
14. The specific dynamic action of food is due to:
a. an increase in core body temperature
b. amino acid metabolism in the liver

c. energy expenditure during digestion
d. hypothalamic sympathetic stimulation
e. secretion of insulin
15. The basal metabolic rate:
a. is about 500 kcal/ kg body weight / day
b. is measured during exercise
c. is measured during exposure to cold environment
d. rises during menstruation and lactation
e. is usually measured two hour following a meal
16. All the following conditions are expected to increase the rate of
metabolism in a young woman EXCEPT:
a. Fasting
b. Fever
c. Menstruation
d. Second trimester of pregnancy
e. Cold environment
17. The respiratory exchange ratio is:
a. The ratio of CO2 production to O2 consumption during steadystates
b. Used to calculate the joule equivalent
c. Used to calculate oxygen debt of organs
d. Negative for the stomach during active secretion of HCL
e. Negative for the brain at rest
18. The metabolic rate is increased by all of the following except:
a. Rise in body temperature
b. Rise in environmental temperature
c. Increased sympathetic outflow
d. Stress
e. Hyperfunction of the thyroid gland
19. Which of the following is the main consumer of energy under basal
conditions?
a. Heart activity
b. Respiratory muscle activity
c. Sodium-potassium pump
d. Skeletal muscle activity
e. Liver metabolism

PHYSIOLOGY Short Note 2

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Core 1 ED 3 General Physiology

Edna Adan University

Dr. Abdiaziz Omar

The core of medical physiology (1) – 3rd edition Page 1

The core of medical physiology (1) – 3rd edition Page 2

The core of medical physiology (1) – 3rd edition Page 3

The core of medical physiology (1) – 3rd edition Page 4

The core of medical physiology (1) – 3rd edition Page 5

Fig 2: The cell organelles

The core of medical physiology (1) – 3rd edition Page 6

The core of medical physiology (1) – 3rd edition Page 7

Fig 2: Passive transport

The core of medical physiology (1) – 3rd edition Page 8

Fig 3: Active transport

The core of medical physiology (1) – 3rd edition Page 9

 Other transport mechanisms

The core of medical physiology (1) – 3rd edition Page 10

 Transport proteins "carriers, pumps & ion channels"

The core of medical physiology (1) – 3rd edition Page 11

The core of medical physiology (1) – 3rd edition Page 12

The core of medical physiology (1) – 3rd edition Page 13

The core of medical physiology (1) – 3rd edition Page 14

The core of medical physiology (1) – 3rd edition Page 15

Table1.1: % of TBW in males and females of different ages

 Body Fluid Compartments

The core of medical physiology (1) – 3rd edition Page 16

The core of medical physiology (1) – 3rd edition Page 17

Table 1.2: Differences between ECF and ICF in a 70 kg adult male

Difference Extracellular fluid Intracellular fluid

Volume 15L 25L

Osmolarity 280-300 mOsm/L 280-300 mOsm/L

The core of medical physiology (1) – 3rd edition Page 18

The core of medical physiology (1) – 3rd edition Page 19

The core of medical physiology (1) – 3rd edition Page 20

Factors Affecting Body Fluid Compartments

The core of medical physiology (1) – 3rd edition Page 21

Osmolarity, Osmolality & Tonicity

The core of medical physiology (1) – 3rd edition Page 22

Fig 1.2: The osmotic pressure

Osmotic pressure prevents

The core of medical physiology (1) – 3rd edition Page 23

The core of medical physiology (1) – 3rd edition Page 24

Table 1.3: Effects of I.V. solutions on volumes and osmolarities

Isotonic The same The same The same

- From the above table:

The core of medical physiology (1) – 3rd edition Page 25

B. From the Molarity

The core of medical physiology (1) – 3rd edition Page 26

Q: Calculate the osmolality of a solution containing 110 mmol NaCl,

The core of medical physiology (1) – 3rd edition Page 27

3- Gibbs Donnan equilibrium

The core of medical physiology (1) – 3rd edition Page 28

From the above relationships:

The core of medical physiology (1) – 3rd edition Page 29

Effects of Donnan equilibrium in the body:

The core of medical physiology (1) – 3rd edition Page 30

Table 1.2: Differences between plasma and ISF in an adult male

Difference Plasma Interstitial fluid