INTRODUCTION TO HUMAN PHYSIOLOGY

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 General introduction
What is Physiology?
Fields of Physiology:
Human physiology (cell physiology, CV physiology, renal,
respiratory, GIT, endocrine, CNS physiology etc)

Historical background: physiology as an experimental

science
William Harvey in 1628, correctly described the direction of
circulation of blood
Claud Bernard(one of the greatest of all men of science), a French
physiologist in the 19th C. described that every cell in body is bathed with the
fluid environment called ECF. ECF contains all the needed substances for cells.
He called ECF is the internal environment of the body, Mileue
interieore.
Walter cannon, another great physiologist of the 1st half of 19th century, termed
the maintenance of constant conditions in the ECF as homeostasis .
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 General introduction
•Relationship b/n Physiology and other sciences
-Physiology has a strong link with other
disciplines of biomedical sciences
•Physiology as a quantitative science
-All physiological parameters are expressed in
numbers

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The fluid environment of the body

• 60% of human body is made up of fluid

• Body fluid is distributed in 2 compartments
1. Intracellular fluid compartment (ICF)
2. Extracellular fluid compartment (ECF)

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 Fluid compartments

ECF
ICF
• Water
• High Na+, Cl- , Ca2+ and
HCO3- •Water
• Nutrients: glucose, aa, lipids •High K+, Po43-,
• Gases: O2, CO2 Mg2+
•Nutrients, gases
• Hormones •Hormones
• Enzymes

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 Composition of Human Body
The approximate composition of an average adult human per
body weight is that
• Water = 60%
• Proteins = 18%
• Fats = 15%
• Minerals = 7%

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 Homeostasis
• The term homeostasis is used by physiologists to mean that
maintenance of static or constant conditions in the internal
environment (ECF).
• Essentially all organs of the body perform their functions to
maintain constant conditions in the ECF.
For example
– Lungs maintain the normal concentration of respiratory gases in
blood.
– The CVS transports required substances and removes waste produces,
– The kidneys maintain constant ionic concentration and
– The GIT provides nutrients.

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Regulatory systems of homeostasis
• The nervous system and the endocrine system are the two
controlling bodies of homeostasis
1. The nervous regulatory mechanism
• The nerves system is composed of three major components
– the sensory portion, the integrative portion and the motor
portion.
• The sensory receptor detects any change in the body (BGC, BT, BP, pain etc)
and send impulse to the brain, spinal cord (CNS).
• The CNS associate the information store some, generate thought and send
appropriate response to the effecter organs (muscle + glands) through the
motor system.

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Regulatory systems of homeostasis
2. The hormonal regulatory mechanism
• Hormones are chemical messengers secreted by endocrine
glands, and transported in blood to the target gland (organs).
Examples:
– Parathyroid hormone  acts on the kidney, bone, intestine =
[Ca2+]
– Aldosterone  acts on the kidney, intestine and  [Na+]
– Anti diuretic hormone(ADH) → acts on kidneys to promote re-
absorption of water.
 An organism is said to be in homeostasis when its internal environment
contains an optimum amount of nutrients, gases, electrolytes, water,
hormones, enzymes and temperature.

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Ca-homeostasis

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 Blood glucose homeostasis
1.
• The L
i
• Glyco ver IT
g
• Glyco enesis 2. G u c o s e
Glu geno Gl p t ion
r
co n l
eog ysis abso
en e
sis
Normal BGC 4. Brain
80-120 mg/dl All neurons
Feeding center

K id n eys
3. se
Gluco ption
r
reabso
5. Hormones
Hyperglycemic hormones
Hypoglycemic hormones

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 Homeostatic values
1. Body fluid volume = 40 L
ECF = 15L
ICF = 25L
2. Osmolality = 300 mosm/L, (285 – 300 mosm/L)
3. Body T. = 36.3 – 37.1OC
4. pH = 7.35 – 7.45
5. Blood Gases
PCO2 = 35 – 45 mm Hg
PO2 = 40 – 104 mm Hg
6. Electrolytes (ECF)
Ca2+ = 10 mg/dL or 5 meq/L
K+ = 4 meq/L
Na+ = 142 meq/L
Cl- = 103 meq/L
HCO3- = 27 meq/L
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 Homeostatic values
7. Waste Products
Bilirubin = 0.5 mg/dl
Creatinine = 0.6 – 1.5 mg/dL
Blood urea nitrogen (BUN) = 8 – 25 mg/dL
Uric acid (s): Women = 2.3 – 6.6 mg/dL
Men = 3.6 – 8.5 mg/dL
8. Blood Glucose level (fasting): 70 – 110 mg/dL
9. Arterial Blood pressure (systemic circulation).
Systolic pressure = 120 mm Hg (90 – 140 mm
Hg)
Diastolic pressure = 80 mm Hg (60 – 90 mm
Hg)
Pulse pressure = 40 mm Hg
Mean BP = 96 mm Hg
Pulmonary AP = 25/10
Cardiac output = 5 L/min
Blood Flow = 5 L /min
10. RBC count = 4-6 millions/mm3
11. WBC count = 4000-11,000/mm3
12. Hb = 12-18
Yohannes M g/dl in F, 14-20 g/dl in M 13
•
 Feedback control mechanisms of the homeostasis

There are two types of feed back mechanisms:

a. The Negative Feedback Mechanism (NFM)
b.The Positive Feedback Mechanism (PFM)

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Negative Feedback Mechanism (NFM)
• It works by producing an effect which opposes the previous
condition (the initiating stimulus) of the organ.
• For example: if the PCO2 is increased in the blood, the NFM
stimulates PVR, which has an effect on decreasing PCO2 in
blood to normal.
• In general, if some factors (parameters) become excessive or
too little, a control system initiates the NFM, which consists
of a series of changes that returns the factors toward certain
mean values (set point or normal values), thus, maintaining
homeostasis.
• Most homeostatic values of the body are controlled by
NFM.
1. Control of ABP
2. Control of BGL
3. Control of BT
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The Positive Feedback Mechanism (PFM)
• It works by producing an effect which enhances or repeats the
same action like that of the starting stimulus.
• The PFM also called viscous circle. Most of the action of this
mechanism disturbs the internal environment and cause
disease and death.
• Fore example, if a person suffers from a heart attack that
damages the heart function, then the heart pumps less amount
of blood to the tissues including the heart muscle and brain.
• If the heart muscle does not get sufficient nutrients and O2, the
activity of the heart becomes weaker and weaker and the
weaker the heart the lesser blood is pumped and then death
may occur.

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 Examples of the PFM
• Blood clotting is an example of a very valuable use of PFM.
• Generation and propagation of the action potential.
Stimulated nerve fiber  opening of Na+ channels 
entry of few Na+ stimulates the opening of more and
more Na+ channels.
• Labor during child birth, uterine contraction is enhanced as the
head of the baby stretches the cervix.
• LH-surge

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Structural levels of organization of human body
Muscle cells
Nerve cells
Cells: 4 types Epithelial cells
Cells in the connective tissues
Muscle tissue
Tissues4 types Nerve tissue
Epithelial tissue
connective tissues
Organs: Example: Heart, lungs

Organ system: Example: Respiratory system, CVS

Organism: Human organism

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 Generalized cell
• There are about 100 trillion cells in a human being.
• Each of the 100 trillion cells in a human being is a living
structure that can survive for months or many years, provided
its surrounding fluids contain appropriate nutrients.
• Of the 100 trillion cells 25 trillion are RBCs.
• A basic knowledge of cell biology is essential to an
understanding of the organ systems in the body and the way
they function(physiology).
• The specialization of the cells in the various organs is very
great, and no cell can be called "typical" of all cells in the
body.
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 Generalized Cell

Components of cells
• Cell has two parts: nucleus and cytoplasm.
• The nucleus is separated from the cytoplasm by a nuclear
membrane and
• The cytoplasm is separated from the surrounding fluid (ECF)
by the plasma membrane.
• The different substances that make up the cell are
collectively called protoplasm.
• Protoplasm is composed mainly of five basic substances:
water, electrolytes(ions), proteins, lipids, and carbohydrates.
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 Generalized Cell
Water:
• The principal fluid medium of the cell is water, which is present in most
cells, except for fat cells, in a concentration of 70 to 85 per cent.
• Many cellular chemicals are dissolved in the water. Others are suspended
in the water as solid particulates.
• Chemical reactions take place among the dissolved chemicals or at the
surfaces of the suspended particles or membranes.
Electrolytes:
• The most important ions in the cell are potassium, magnesium,
phosphate, sulfate, bicarbonate, and there are also smaller quantities
of sodium, chloride, and calcium.
• These are important for the interrelations between the intracellular and
extracellular fluids.
• They also provide inorganic chemicals for cellular reactions. Moreover,
they are necessary for operation Yohannes
of some M of the cellular control 21
 Generalized Cell
Proteins
• After water, the most abundant substances in most cells are
proteins, which normally constitute 10 to 20 per cent of the
cell mass.
• They can be divided into two types: structural proteins and
functional proteins.
• Structural proteins are present in the cell mainly in the form of
long filaments.
• The functional proteins are an entirely different type of protein,
usually composed of combinations of a few molecules in
tubular-globular form. These proteins are mainly the enzymes
of the cell and, in contrast to the fibrillar proteins, are often
mobile in the cell fluid. Yohannes M 22
 Generalized Cell

Lipids:
• Lipids are several types of substances that are grouped
together because of their common property of being soluble in
fat solvents.
• Especially important lipids are phospholipids and cholesterol,
which together constitute only about 2 per cent of the total cell
mass.
• In addition to phospholipids and cholesterol, some cells contain
large quantities of triglycerides, also called neutral fat. The fat
stored in these cells represents the body’s main storehouse of
energy-giving nutrients that can later be dissoluted and used to
provide energy wherever in the body it is needed.
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 Generalized Cell
Carbohydrates:
• Carbohydrates have little structural function in the cell except
as parts of glycoprotein molecules, but they play a major role
in nutrition of the cell.
• Most human cells do not maintain large stores of
carbohydrates; the amount usually averages about 1% of their
total mass but increases to as much as 3 per cent in muscle
cells and, occasionally, 6 per cent in liver cells.
• Carbohydrate in the form of dissolved glucose is always
present in the surrounding extracellular fluid so that it is
readily available to the cell.

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 PARTS FUNCTIONS
Centrioles found within the centrosome; aid in reproduction
Centrosome contain the centrioles; aid in reproduction
Golgi body (complex) manufactures carbohydrates and packages it with protein
Nucleus control center
Nucleolus produces ribosomes and RNA
Nuclear membrane allows material in and out of the nucleus
Nucleoplasm gives the nucleus shape
Plasma (cell) membrane allows material in and out of the cell
Microvilli projections that increase cell's surface area
Mitochondria produce energy
Cytoplasm gives the cell shape and holds the organelles
Lysosome contain digestive enzymes
smooth ER synthesize lipids (without ribosomes)
rough ER transports material through cell ( with ribosomes)
Ribosomes produces protein
indentation in the cell membrane that allows for entrance of
Pinocytic vessicle
large molecule
Vacuole storage areas for food and/or water
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 Membranous Structures of the Cell

• Most organelles of the cell are covered by membranes

composed primarily of lipids and proteins.
• These membranes include the cell membrane, nuclear
membrane, membrane of the endoplasmic reticulum, and
membranes of the mitochondria, lysosomes, and Golgi
apparatus.
• The lipids of the membranes provide a barrier that
impedes the movement of water and water-soluble
substances from one cell compartment to another.

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 The plasma membrane
• It is a sheet-like structure that surround (enclose) the
cell, separating the cellular contents from the ECF.
• It is entirely composed of proteins and lipids in a
ratio of 55:43 respectively, and 3% of carbohydrates.
Percent proportion:
1. Proteins: 55 %
• Phospholipids 25
%
2. Lipids: 42 % Cholesterol 13
%
• Neutral fats 4
%
3. Carbohydrate: 3 %
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 Function of the plasma membrane
1. Separates cellular contents from the
ECF
2. Regulates the passage of substances
in and out. It is semi-permeable
allowing some subs to pass through it
excluding others. This creates
unequal distribution of ions on both
sides of the membrane.
3. It provides receptors for
neurotransmitters, hormones and
drugs.
4. It is a means of cell to cell contact.
5. Plays an important role in the
generation and transmission of
electrical impulse in nerves muscle.
6. Involved in the regulation of cellYohannes M 28
 Lipid component of the cell membrane
• A plasma membrane is a fluid in its nature,
according to the fluid Mosaic model of the
membrane. ECF
• The cell membrane consists of an organized
arrangement of proteins, lipids and CHOs.
• The major lipids are phospholipids such as
phosphatidyl choline and phosphatidyl-
ethanolamine, and cholesterol.
• Lipids form the basic structure of the
membrane.
• The lipid molecules are arranged in two
parallel rows, forming a lipid bilayer.
ICF

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 The plasma membranecont’d
• It is believed that globular proteins are embedded in
the lipid bilayes and that these proteins participate in
the transport of lipid-insoluble particles through the
plasma membrane, some integral proteins act as
carriers and channels.
• The cell membrane is surrounded by a cell coat or
glycocalyx, which is made up of glycolipids and
glycoproteins.
• The cell coat is the site of hormonal receptors and
antigenic activity in ABO blood groups.

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 The plasma membranecont’d
• The phospholipids
component is organized into
a double layer with their
hydrphophic (tail) directed
toward the center of the
membrane and polar heads
directed out ward facing
ECF and ICF.
• Because the hydrophobic
portions of the phospholipid
molecules are repelled by
water but are mutually
attracted to one another, they
have a natural tendency to
attach to one another in the
middle of the membrane. Yohannes M 31
 The plasma membranecont’d
• The lipid molecules (primarily phospholipids) contain
a polar phosphate heads, soluble in water
(hydrophilic) and a non-polar tails that does not mix
with water (hydrophobic).
• The physical orientation of the lipid bilayer structures
is that the hydrophilic ends of the lipid molecules line
up facing the ICF and ECF.
• The hydrophobic tails of the molecules face each
other in the interior of the bilayer.
• The lipid bilayer portion of the cell membrane is
impermeable to water and water soluble substances
such as ions, glucose, urea and others. On the other
hand, fat soluble substances such as O2, CO2, alcohol
and drugs can penetrateYohannes
thisMportion of the membrane.32
 Membrane proteins
• Are globular masses floating in the lipid bilayer.
• Most of the membrane proteins are found in the form of glycoproteins.
Types
A. Integral or intrinsic proteins: are found deep in the hydrophobic
center of the lipid bilayer
• Transmembrane proteins are integral proteins that span the entire
bilayer. Transmembrane proteins serve as:
‾ Channels through which ions pass. These protein channels also have
selective properties that allow preferential diffusion of some substances
over others.
‾ Carriers which actively transports material across the bilayer e.g.
glucose.
‾ Pumps which actively transport ions
‾ Receptors for water soluble chemicals( neurotransmitters and hormones).
• Integral proteins that are present only on one side of the membrane,
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serve primarily as enzymes.
Membrane proteins: channels

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 Membrane proteinscont’d
B. Peripheral proteins: bind
to the hydrophilic polar
heads of the lipid or on
integral proteins.
• Peripheral proteins that bind
to the intracellular surface
contribute to the
cytoskeleton.
• Peripheral proteins that bind
to the external surface
contribute to the glyco-
calyx, a cell coat that is
composed of glycol-lipids
and glycol-proteins to cover
the cell membrane. Yohannes M 35
 Membrane carbohydrates
• Attached invariably on the outside surface of the membrane, binding
with protruded integral proteins and lipid, they form glycoproteins and
glycolipid respectively.
• Many other carbohydrate compounds, called proteoglycans, which are
mainly carbohydrate substances bound to small protein cores, are loosely
attached to the outer surface of the cell as well.
• Thus, the entire outside surface of the cell often has a loose carbohydrate
coat called the glycocalyx.
• Membrane CHOs play a role in:
1. Immune reaction (antigenical importance),
2. Cell to cell attachment
3. Act as receptors for NTs, hormones and drugs
4. Many of them have a negative electrical charge, which gives most cells
an overall negative surface charge that repels other negative substances.
• In fact, most of the integral proteins are glycoproteins, and about one tenth
of the membrane lipid molecules Yohannes
are glycolipids.
M 36
 The nucleus
• The nucleus is the control center for the cells. If a cell is cut in
half, the anucleate portion eventually dies without dividing.
• It contains the genes, which are units of heredity.
• Chemically, genes are part of highly compressed DNA in the
form of chromosomes
• Genes control cellular activity by determining the type of
proteins, enzymes, and other substances that are made by the
cell.
• The nucleus is also the site of RNA synthesis.
• There are three kinds of RNA
– Messenger RNA (mRNA), which carries the instruction from
DNA for protein synthesis to the cytoplasm
– Ribosomal RNA (rRNA), which moves to the cytoplasm
where it becomes the site of protein synthesis
– Transfer RNA (tRNA), serves as an amino acid transporter
system within the cell for protein synthesis.
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 The nucleuscont’d
• DNA and RNA are made up of
nucleotides
• Nucleotides are composed of
nitrogen containing bases purine (A,
G) and pyrimidin (C, T) as well as 5
carbon sugar conjugated by
phosphate.
• In RNA, the pyrimidin base T is
replaced by U and the 5-carbon sugar
is ribose.
• The pores present in the nuclear
membrane allow fluids, electrolytes,
RNA, and other materials to move
between the nuclear and cytoplasmic
comportments.
• The interior of the nucleus has a
skeleton of fine filaments that are
attached to the nuclear membrane.
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 The nucleuscont’d
• The nuclei of most cells contain one or more highly staining
structures called nucleoli.
• The nucleolus does not have a limiting membrane. Instead, it is
simply an accumulation of large amounts of RNA and proteins
of the types found in ribosomes.
• The nucleolus becomes considerably enlarged when the cell is
actively synthesizing proteins.
• Formation of the nucleoli (and of the ribosomes) begins in the
nucleus. First, specific DNA genes in the chromosomes cause
RNA to be synthesized. Some of this is stored in the nucleoli,
but most of it is transported outward through the nuclear pores
into cytoplasm. Here, it is used in conjunction with specific
proteins to assemble “mature” ribosomes that play an essential
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role in forming cytoplasmic proteins.
 Nuclear Membrane

• The nuclear membrane, also called the nuclear envelope, is actually two
separate bilayer membranes, one inside the other.
• The outer membrane is continuous with the endoplasmic reticulum of the
cell cytoplasm, and the space between the two nuclear membranes is also
continuous with the space inside the endoplasmic reticulum.
• The membrane is permeable only to small molecules. However, it
contains nuclear pore complexes.
• Each complex has eightfold symmetry and is made up of about 100
proteins organized to form a tunnel through which transport of proteins
and mRNA occurs.
• There are many transport pathways, and proteins called importins and
exportins have been isolated and characterized. A protein named Ran
appears to play an organizing role.
• Much current research is focused on transport into and out of the nucleus,
and a more detailed understanding of these processes are expected to
emerge in the near future. Yohannes M 40
 Nucleotides

Function
1. Building units of nucleic
acid DNA, RNA
2. High energy molecules
(ATP, GTP)
3. Biosynthetic mediators
(UDP-glycogen)
4. Regulator of chemical
reaction in the cell eg.
cAMP
5. Act as coenzyme (NAD,
FAD)

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 Cytoplasm and Its Organelles
• The cytoplasm is filled with both minute and large
dispersed particles and organelles.
• The clear fluid portion of the cytoplasm in which the
particles are dispersed is called cytosol.
• Dispersed in the cytoplasm are neutral fat globules,
glycogen granules, ribosomes, secretory vesicles, and five
especially important organelles: the endoplasmic
reticulum, the Golgi apparatus, mitochondria, lysosomes,
and peroxisomes.
• There are also cytoskeletal system of the cell
(microtabules, intermediate filaments and
microfilaments).
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 Cellular organelles
• Ribosomes:
• small particles composed of rRNA and proteins
• are the sites of protein synthesis in the cell
• found in two forms: attached to the wall of ER or as free
ribosomes.
• Free ribosomes are found in two forms
» scattered in the cytoplasm and
» clustered (aggregated) to form functional units called
polyribosomes
• The ribosomes that become attached to the endoplasmic reticulum
synthesize all transmembrane proteins, most secreted proteins,
and most proteins that are stored in the Golgi apparatus,
lysosomes, and endosomes.
• The free ribosomes synthesize cytoplasmic proteins such as
hemoglobin and the proteins found
Yohannes Min peroxisomes and mitochondria.
43
 Endoplasmic reticulum (ER)
• It is an extensive membranous structure that connects various parts of the
inner cell. ER is also connected with the nuclear membrane.
• The space inside the tubules and vesicles of ER is filled with endoplasmic
matrix, a watery medium that is different from the fluid in the cytosol
outside the endoplasmic reticulum.
• Substances formed in some parts of the cell enter the space of the
endoplasmic reticulum and are then conducted to other parts of the cell.
• Also, the vast surface area of this reticulum and the multiple enzyme
systems attached to its membranes provide machinery for a major share of
the metabolic functions of the cell.
• There are two types of ER: granular or rough ER(rER) and agranular or
smooth ER(sER).
• The rER is studded with ribosomes.
• The function of rER is to segregate proteins that are being exported from the
cell.
• rER is also the site of protein synthesis
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• The sER is free of ribosome.
• Function of sER varies in different Endoplasmic reticulumcont’d
cells.
• The sarcoplasmic reticulum of
skeletal and cardiac muscle cells
are forms of sER.
• Ca++ needed for muscle contraction
are stored and released from the
sarcoplasmic reticulum of muscle
cells.
• In the liver, the sER is involved in
glycogen storage and drug
metabolism.
• ER can synthesize a group of drug
metabolizing enzymes called
microsomal system.
• Function of sER:-
1. Glycogen storage
2. Calcium storage
3. Lipid biosynthesis rER and sER
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4. Drug metabolism (detoxify)
 Golgi Complex

• The Golgi complex consists of

flattened membranous saccules
and cisterns that communication
with the ER and acts as a
receptacle for hormones and
others substances that the ER
produces.
• It then modifies and packages
these substances into secretary
granules.
• The Golgi apparatus is closely
related to the ER.

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 Golgi Complexcont’d

• Small “transport vesicles” (also

called endoplasmic reticulum
vesicles) continually pinch off
from ER and shortly thereafter
fuse with the Golgi apparatus.
• In this way, substances entrapped
in the ER vesicles are transported
from the ER to the Golgi
apparatus.
• The transported substances are
then processed in the Golgi
apparatus to form lysosomes,
secretory vesicles, and other
cytoplasmic components
Yohannes M 47
Rough ER and Golgi complex

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 Lysosomes

• Lysosomes are vesicular organelles that form by breaking

off from the Golgi apparatus and then dispersing
throughout the cytoplasm.
• The lysosomes provide an intracellular digestive system
that allows the cell to digest:
1. damaged cellular structures
2. food particles that have been ingested by the cell, and
3. unwanted matter such as bacteria.
• It is surrounded by a typical lipid bilayer membrane and is
filled with large numbers of small granules which are
protein aggregates of as many as 40 different hydrolase
(digestive) enzymes. Yohannes M 49
 Lysosomes

• Ordinarily, the membrane surrounding the lysosome

prevents the enclosed hydrolytic enzymes from
coming in contact with other substances in the cell
and, therefore, prevents their digestive actions.
• However, some conditions of the cell break the
membranes of some of the lysosomes, allowing
release of the digestive enzymes.
• These enzymes then split the organic substances with
which they come in contact into small, highly
diffusible substances such as amino acids and
glucose.
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 Peroxisomes

• Peroxisomes are similar physically to lysosomes, but they are

different in two important ways.
– First, they are believed to be formed by self-replication (or perhaps by
budding off from the smooth endoplasmic reticulum) rather than from the
Golgi apparatus.
– Second, they contain oxidases rather than hydrolases.
• Several of the oxidases are capable of combining oxygen with
hydrogen ions derived from different intracellular chemicals to form
hydrogen peroxide .
• Hydrogen peroxide is a highly oxidizing substance and is used in
association with catalase, another oxidase enzyme present in large
quantities in peroxisomes, to oxidize many substances that might
otherwise be poisonous to the cell.
• For instance, about half the alcohol a person drinks is detoxified by
the peroxisomes of the liver cells in this manner.
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 Secretory Vesicles

• One of the important functions of many cells is

secretion of special chemical substances.
• Almost all such secretory substances are formed by
the endoplasmic reticulum–Golgi apparatus system
and are then released from the Golgi apparatus into
the cytoplasm in the form of storage vesicles called
secretory vesicles or secretory granules.
• Typical secretory vesicles are seen in areas such as
pancreatic acinar cells, endocrine glands, and the
others.

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 Mitochondria
• The mitochondria are literally the
“power plants” of the cell, capable
of producing the energy rich
compound ATP, which is required
for various cellular activities.
• The mitochondria require oxygen
to produce energy from food stuffs.
• Mitochondria are present in all
areas of each cell’s cytoplasm, but
the total number per cell varies
from less than a hundred up to
several thousand, depending on the
amount of energy required by the
cell. Yohannes M 53
 Mitochondriacont’d
• Has outer and inner membrane.
• Many infoldings of the inner membrane form shelves onto which
oxidative enzymes are attached.
• In addition, the inner cavity of the mitochondrion is filled with a
matrix that contains large quantities of dissolved enzymes that
are necessary for extracting energy from nutrients.
• These enzymes operate in association with the oxidative
enzymes on the shelves to cause oxidation of the nutrients,
thereby forming carbon dioxide and water and at the same time
releasing energy.
• The liberated energy is used to synthesize a high-energy
substance.
• Mitochondria are self-replicative. The rate of replication is
higher whenever there is a need in the cell for increased amounts
Yohannes M 54
 Cytoskeletal system of the cell
• Extending throughout the
cytosol, the cytoskeleton is a
network of three different
types of protein filaments:
microfilaments,
intermediate filaments, and
microtubules.
• The thinnest elements of the
cytoskeleton are the
microfilaments which are
concentrated at the periphery
of a cell and contribute to the
cell’s strength and shape. Yohannes M 55
 Cytoskeletal system of the cell cont’d
• Microfilaments have two general
functions:
– providing mechanical support and
helping generate movements.
– anchor the cytoskeleton to integral
proteins and provide support for
microscopic, fingerlike projections
of the plasma membrane called
microvilli.
• With respect to movement,
microfilaments are involved in
muscle contraction, cell division,
and cell locomotion.
Yohannes M 56
Cytoskeletal system of the cell cont’d
• Microfilament-assisted movements include
– the migration of embryonic cells during development,
– the invasion of tissues by white blood cells to fight infection,
and the migration of skin cells during wound healing.
• As their name suggests, intermediate filaments are
thicker than microfilaments but thinner than
microtubules
• Intermediate filaments are found in parts of cells
subject to tension (such as stretching), help hold
organelles such as the nucleus in place, and help attach
cells to one another.
Yohannes M 57
 Cytoskeletal system of the cell cont’d
• The largest of the cytoskeletal
components, microtubules
are long, hollow tubes.
• Microtubules help determine
cell shape and function in
both the movement of
organelles, such as secretory
vesicles, within a cell and the
migration of chromosomes
during cell division.
• They also are responsible for
movements of cilia and
flagella.
Yohannes M 58
Cytoskeletal system of the cell cont’d
Function of cytoskeletal system:
1. Maintain shape of the cells.
eg. Neurofibrils in axon
2. Serve as a transport system for the
movement of compounds and organelles
within the cell.
Eg. axoplasmic transport
3. Construct the mitotic spindle
eg. Centroils (9+3 triplets)
4. Provide for the support and movement of
cilia and flagella (9+2 doublets)
5. Cell to cell contact: to fasten cell
membranes together
Yohannes M 59
 Clinical correlates
• Microtubules are the target of a number of antitumor drugs
(e.g., vincristine and taxol) because disruption of these
structures impairs cell division in the highly mitotic tumor cells.
• Kartagener's syndrome is an autosomal recessive disorder in
which dynein ( a motor protein that drives the movement of both
cilia and flagella) is missing in cilia and, in males, the flagella of
sperm. Accordingly, males with this syndrome are infertile.
Because the cilia of the epithelial cells that line the respiratory
track work to remove inhaled pathogens, a process termed
mucociliary transport, both men and women with this
syndrome are susceptible to repeated lung infections.

Yohannes M 60
 Transport through the cell membrane
• Substances are
transported through
the cell membrane
by:
ECF
1. Simple diffusion
2. Osmosis
3. facilitated diffusion
ICF
4. active transport (1O
and 2O) and
5. vesicular transport
mechanisms.

Yohannes M 61
 Simple Diffusion
• Diffusion is passive movement of substances down their
concentration gradient.

• Rate of diffusion is determined by the following factors

summarized in the formula shown below.
• S. A. T. C
• Rate of diffusion =
D MW

Where, C = Change of concentration

S = Solubility in lipid
A = Surface area of the membrane
T = Temperature
D = Distance or membrane thickness
MW = Molecular wt of substances

• Substances that are transported byMsimple diffusion are CO 2, O2,

Yohannes 62
 Osmosis
• It is the power of movement of H2O
from an area of higher amount of
water to an area of lower amount of
water through the semi permeable
membrane.
• The direction of movement of water
is governed by the amount of
osmoticaly active particles (solutes).
• The pressure that opposes osmosis of
water is called osmotic pressure. It is
the exact amount of pressure
required to stop osmosis.
• H2O molecules are polar, so that they
can not traverse the lipid bilayer
simply. Instead they pass through
specific water channels called
aquaporins: Five different types of
aquapurins (AQ1….AQ5) haveYohannesbeenM 63
identified in the body.
 Osmolality —The Osmole

• To express the concentration of a solution in terms of numbers

of particles, the unit called the osmole is used in place of grams.
• One osmole is 1 gram molecular weight of osmotically active
solute. Thus, 180 grams of glucose, which is 1 gram molecular
weight of glucose, is equal to 1 osmole of glucose because
glucose does not dissociate into ions.
• Conversely, if a solute dissociates into two ions, 1 gram
molecular weight of the solute will become 2 osmoles because
the number of osmotically active particles is now twice as great
as is the case for the nondissociated solute.
• Therefore, when fully dissociated, 1 gram molecular weight of
sodium chloride, 58.5 grams, is equal to 2 osmoles.
Yohannes M 64
 Facilitated diffusion

• Is Carrier mediated diffusion

Glucose

ECF
Cell membrane

ICF

Carrier protein

Yohannes M 65
• There are times at which a large
concentration of a substance is Active transport
required in the intracellular fluid
even though the extracellular fluid
contains only a small conc. This is Common examples
true, for instance, for potassium 1. Na+ - K+ ATPase
ions. 2. H+ - K+ ATPase
3. Ca2+ ATPase
• Conversely, it is important to keep
the concentrations of other ions
very low inside the cell even
though their concentrations in the
extracellular fluid are great. This is
especially true for sodium ions.
• Neither of these two effects could
occur by simple diffusion, because
simple diffusion eventually
equilibrates concentrations on the
two sides of the membrane. Yohannes M 66
 Primary active transport

• Active transport is divided into two types according to the source of

the energy used to cause the transport: primary active transport and
secondary active transport.
• In primary active transport, the energy is derived directly from
breakdown of ATP or of some other high-energy phosphate
compound. In secondary active transport, the energy is derived
secondarily from energy that has been stored in the form of ionic
concentration differences of secondary molecular or ionic substances
between the two sides of a cell membrane, created originally by
primary active transport.

Features of primary active transport

- Carrier protein in involved
- Consumes energy from ATP Yohannes M 67
Yohannes M 68
 Secondary active transport
• When sodium ions are transported out
of cells by primary active transport, a
large concentration gradient of sodium
ions across the cell membrane usually
develops—high concentration outside
the cell and very low concentration
inside.
• This gradient represents a storehouse of
energy because the excess sodium
outside the cell membrane is always
attempting to diffuse to the interior.
• Under appropriate conditions, this
diffusion energy of sodium can pull
other substances along with the sodium
through the cell membrane. This
phenomenon is called co-transport; it is
one form of secondary active transport.
Yohannes M 69
 Clinical correlates
• Cystic fibrosis is an autosomal recessive disease
characterized by chronic lung infections, pancreatic
insufficiency, and infertility in males.
• It is caused by defective chloride ion channel which causes
impeding of mucocilliary transport in respiratory tract.
• Inflamation occurs because of dust and bacteria
accumulation in the tract.
• The inflammatory process that accompanies these
infections ultimately destroys the lung tissue and causes
respiratory failure and death.
• It is most prevalent in the white population, occurring in 1
in 3000 live births, and is the most common lethal genetic
disease in this population. Yohannes M 70
 Vesicular transport
• Solute and water can be brought into the cell by the process of
endocytosis and released from the cell by the process of
exocytosis.
• In both processes the integrity of the plasma membrane is
maintained, and the vesicles that are formed allow transfer of the
contents between cellular compartments.
• In some cells (e.g., the epithelial cells lining the gastrointestinal
tract), endocytosis across one membrane of the cell is followed
by exocytosis across the opposite membrane. This allows the
transport of substances across the epithelium, a process termed
transcytosis.
• Endocytosis:
a. Pinocytosis
Yohannes M 71
b. Phagocytosis
 Intercellular connections
1. Tight junctions
• Tight junctions characteristically surround the apical margins of the
cells in epithelia such as the intestinal mucosa, stomach, the walls of
the renal tubules, and the choroid plexus where materials are
required to pass transcellularly.
2. Desmosomes
• Desmosomes are patches characterized by apposed thickenings of the
membranes of two adjacent cells.
3. Hemidesmosomes
• Hemidesmosomes look like half-desmosomes that attach cells to the
underlying basal lamina and are connected intracellularly to
intermediate filaments.
4. Gap junctions(communicating junctions)
• Are important for exchange of Yohannes
molecules
M
and ions between cells. 72
 Intercellular communicationscont’d
• Extracellular signaling molecules, or messengers, mediate four
kinds of communication: contact dependent, endocrine,
paracrine and synaptic communication.
– Contact-dependent signaling is important during development and
in immune responses.
– In endocrine signaling , hormones are carried in the blood to
target cells (ie, cells with specific receptors to a hormone)
throughout the body;
– In paracrine signaling , chemical mediators are rapidly
metabolized so that they act on local cells only; and
– In synaptic signaling , neurotransmitters act only on adjacent
nerve cells through special contact areas called synapses.
• In some cases, paracrine signals act on the same cell type that
produced the messenger molecule, a phenomenon called
Yohannes M 73
autocrine signaling.
Intercellular signaling

Yohannes M 74
 Cell Receptors
• All signaling molecules bind to specific receptors that act as signal
transducers, thereby converting a ligand-receptor binding event into
intracellular signals that affect cellular function.
• Receptors can be divided into two basic classes based on their structure
and mechanism of action: plasma membrane receptors and nuclear
receptors.
• There are four major types of plasma membrane receptors defined by the
intracellular signaling pathways that they use:
1. Ion channel-linked receptors( also called ligand gated ion channels-
mediate direct and rapid synaptic signaling between electrically excitable
cells. Neurotransmitters bind to the receptors and either open or close the
ion channel, thereby changing the ionic permeability of the plasma
membrane and altering the membrane potential. For example, activation of
the ryanodine receptor (RyR), located in the membrane of the sarcoplasmic
reticulum of skeletal muscle, by Ca++, caffeine, ATP, or metabolites of
arachidonic acid releases Ca++ into the cytosol, which facilitates muscle
Yohannes M 75
contraction
 Cell receptorscont’d
2. G protein-coupled receptors (GPCRs)- GPCRs regulate the
activity of other proteins, such as enzymes and ion channels. In this
type of receptor the interaction between the receptor and the target
protein is mediated by heterotrimeric G proteins, which are
composed of α, β, and γ subunits. Stimulation of G proteins by
ligand-bound receptors activates or inhibits downstream target
proteins that regulate signaling pathways if the target protein is an
enzyme or change membrane ion permeability if the target protein is
an ion channel.
3. Catalytic receptors- Catalytic receptors either function as
enzymes or are associated with and regulate enzymes .
Most enzyme-linked receptors are protein kinases or are associated
with protein kinases, and ligand binding causes the kinases to
phosphorylate a specific subset of proteins on specific amino acids,
which in turn activates or inhibits
Yohannesprotein
M activity. 76
 Cell receptors cont’d
4. A fourth class of transmembrane receptors that when activated,
release transcription factors that undergo proteolytic cleavage and
liberate a cytosolic fragment that enters the nucleus and modulates
gene expression.
Nuclear receptors - are receptors for lipophilic substances such as
steroidal hormones, thyroid hormones and vitamin D.
 Several diseases have been shown to be due to defective
receptors. For example, pseudohypoparathyroidism and a
type of dwarfism are due to nonfunctioning parathyroid and
growth hormone receptors. In these two conditions the
glands produce the respective hormones, but the target cells
do not respond, because they lack normal receptors.
Yohannes M 77
Yohannes M 78