2. General introduction
What is Physiology?
Fields of Physiology:
Human physiology (cell physiology, CV physiology,
renal, respiratory, GIT, endocrine, CNS
physiology etc)
• 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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3. 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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4. Fluid compartments
ECF
• Water
• High Na+, Cl- , Ca2+ and
HCO3
-
• Nutrients: glucose, aa, lipids
• Gases: O2, CO2
• Hormones
• Enzymes
4
•Water
•High K+, Po4
3-,
Mg2+
•Nutrients, gases
•Hormones
ICF
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5. 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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6. 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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7. 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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8. 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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12. 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 g/dl in F, 14-20 g/dl in M
• Deviations in normal ranges = pathology 12
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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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14. 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 14
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15. 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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16. 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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17. 17
Structural levels of organization of human body
Muscle cells
Nerve cells
Cells: 4 types Epithelial cells
Cells in the connective tissues
Muscle tissue
Tissues 4 types Nerve tissue
Epithelial tissue
connective tissues
Organs: Example: Heart, lungs
Organ system: Example: Respiratory system, CVS
Organism: Human organism
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18. 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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19. 19
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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20. 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 of some of the cellular
control mechanisms.
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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. 21
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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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23. 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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24. 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
Pinocytic vessicle
indentation in the cell membrane that allows for entrance of
large molecule
Vacuole storage areas for food and/or water 24
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25. 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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26. 26
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 %
The level of cholesterol determines fluidity of the
membrane
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27. 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 cell
growth and proliferation.
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28. 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.
• 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
ECF
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29. 29
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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30. 30
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.
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31. 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 penetrate this portion of the membrane.
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32. 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,
serve primarily as enzymes.
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34. 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.
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35. 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 are glycolipids.
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36. 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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37. 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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38. 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
role in forming cytoplasmic proteins.
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39. 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. 39
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40. 40
Nucleotides
Function
1. Building units of nucleic
acid DNA, RNA
2. High energy molecules
(ATP, GTP)
3. Biosynthetic mediators
4. Regulator of chemical
reaction in the cell eg.
cAMP
5. Act as coenzyme (NAD,
FAD)
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41. 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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42. 42
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 in peroxisomes and
mitochondria.
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43. 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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44. 44
Endoplasmic reticulumcont’d
• The sER is free of ribosome.
• Function of sER varies in different
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
4. Drug metabolism (detoxify)
rER and sER
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45. 45
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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46. 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
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48. 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.
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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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50. 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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51. 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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52. 52
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.
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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
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54. 54
Transport through the cell membrane
• Substances are
transported through
the cell membrane
by:
1. Simple diffusion
2. Osmosis
3. facilitated diffusion
4. active transport (1O
and 2O) and
5. vesicular transport
mechanisms.
ECF
ICF
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55. 55
Simple Diffusion
• Diffusion is passive movement of substances down their
concentration gradient.
• Diffusion never ceases under any condition except at absolute
zero temperature.
• Simple diffusion can occur through the cell membrane by
two pathways:
1. through the interstices of the lipid bilayer if the
diffusing substance is lipid soluble - Oxygen is transported
in this way. Oxygen can be delivered to the interior of the
cell almost as though the cell membrane did not exist.
2. through watery channels. Even though water is highly
insoluble in the membrane lipids, it readily passes through
channels in protein molecules that penetrate all the way
through the membrane.
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56. Simple Diffusion
• The rapidity with which water molecules can move through
most cell membranes is astounding. As an example, the total
amount of water that diffuses in each direction through the red
cell membrane during each second is about 100 times as great
as the volume of the red cell itself.
• Other lipid-insoluble molecules can pass through the protein
pore channels in the same way as water molecules if they
are water soluble and small enough. However, as they
become larger, their penetration falls off rapidly.
• For instance, the diameter of the urea molecule is only 20 per
cent greater than that of water, yet its penetration through the
cell membrane pores is about 1000 times less than that of
water. Even so, given the astonishing rate of water
penetration, this amount of urea penetration still allows rapid
transport of urea through the membrane within minutes. 56
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57. Simple Diffusion
Factors affecting the net rate of diffusion
– Lipid solubility of the subs
– Membrane permeability
– Concentration difference or Pressure difference
– Electrical potential difference of ions
Membrane permeability is affected by
– Membrane Thickness
– Lipid solubility
– No of ion channels per unit area
– Temperature: T = thermal motion of molecule
permeability
– MW
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58. 58
Simple Diffusion
• 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 by simple diffusion are CO2,
O2, alcohol, lipid soluble drugs and ions through specific
channels.
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59. Diffusion Through Protein Channels
• The protein channels are distinguished by two important
characteristics:
• 1. selectively permeability. Many of the protein channels
are highly selective for transport of one or more specific
ions or molecules. This results from the characteristics of
the channel itself, such as its diameter, its shape, and the
nature of the electrical charges and chemical bonds along
its inside surfaces.
• 2. presence or absence of gates. Gating of protein
channels provides a means of controlling ion permeability
of the channels. The opening and closing of gates are
controlled in two principal ways:
a. Voltage gating.
b. Chemical (ligand) gating.
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60. 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) have been
identified in the body.
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61. 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.
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62. 62
Facilitated diffusion
• Carrier mediated transport
• Carriers are saturable, do not need
energy
• Transports substances down their
concentration gradient.
• Facilitated diffusion differs from
simple diffusion in the following
important way:
– Although the rate of simple
diffusion through an open channel
increases proportionately with the
concentration of the diffusing
substance, in facilitated diffusion
the rate of diffusion approaches a
maximum, called Vmax, as the
concentration of the diffusing
substance increases.
• Examples: transport of glucose,
proteins. (Macromolecules)
Glucose
Carrier protein
Cell membrane
ECF
ICF
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63. 63
Active transport
• There are times at which a large
concentration of a substance is
required in the intracellular fluid
even though the extracellular fluid
contains only a small conc.
• This is true, for instance, for
potassium ions.
• 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.
Common examples
1. Na+ - K+ ATPase
2. H+ - K+ ATPase
3. Ca2+ ATPase
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64. Active transport
• Instead, some energy
source must cause excess
movement of potassium
ions to the inside of cells
and excess movement of
sodium ions to the
outside of cells.
• In active transport,
substances are
transported against
concentration,
electrochemical gradient,
up hill direction.
• Used for the transport of
Na+, K+, Ca2+, Fe2+, H+,
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65. Primary Active Transport of Hydrogen Ions
• At two places in the body, primary active transport of
hydrogen ions is very important:
– in the gastric glands of the stomach, and
– in the late distal tubules and cortical collecting ducts of the
kidneys.
• In the gastric glands, the deep-lying parietal cells have the
most potent primary active mechanism for transporting
hydrogen ions of any part of the body.
• This is the basis for secreting hydrochloric acid in the
stomach digestive secretions.
• At the secretory ends of the gastric gland parietal cells, the
hydrogen ion concentration is increased as much as a
millionfold and then released into the stomach along with
chloride ions to form hydrochloric acid.
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67. Primary Active Transport of Hydrogen Ions
• In the renal tubules are special intercalated cells in
the late distal tubules and cortical collecting ducts
that also transport hydrogen ions by primary active
transport.
• In this case, large amounts of hydrogen ions are
secreted from the blood into the urine for the purpose
of eliminating excess hydrogen ions from the body
fluids.
• The hydrogen ions can be secreted into the urine
against a concentration gradient of about 900-fold.
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68. 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.
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69. Secondary active transportcont’d
• For sodium to pull another substance along with it, a
coupling mechanism is required. This is achieved by
means of still another carrier protein in the cell
membrane.
• The carrier in this instance serves as an attachment
point for both the sodium ion and the substance to be
co-transported.
• There are three different types of carriers:
– Uniport carriers: Carry single substance to one direction
– Antiport carriers: Carry two substances in opposite
directions
– Symport carriers: Carry two substances into the same
direction 69
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70. Co-Transport of Glucose and Amino Acids
Along with Sodium Ions
• Glucose and many amino acids are transported into most cells against
large concentration gradients; the mechanism of this is entirely by co-
transport.
• This transport carrier protein has two binding sites on its exterior
side, one for sodium and one for glucose.
• Also, the concentration of sodium ions is very high on the outside and
very low inside, which provides energy for the transport.
• A special property of the transport protein is that a conformational
change to allow sodium movement to the interior will not occur until a
glucose molecule also attaches.
• When they both become attached, the conformational change takes
place automatically, and the sodium and glucose are transported to the
inside of the cell at the same time. Hence, this is a sodium-glucose
co-transport mechanism.
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71. Co transport of glucose and cont’d
• Sodium co-transport of the amino acids occurs in the
same manner as for glucose, except that it uses a
different set of transport proteins.
• Five amino acid transport proteins have been identified,
each of which is responsible for transporting one subset
of amino acids with specific molecular characteristics.
• Sodium co-transport of glucose and amino acids occurs
especially through the epithelial cells of the intestinal
tract and the renal tubules of the kidneys to promote
absorption of these substances into the blood.
• Other important co-transport mechanisms in at least
some cells include co-transport of chloride ions, iodine
ions, iron ions, and urate ions.
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72. Sodium Counter-Transport of Ca++ and H+
• Two especially important counter-transport mechanisms are sodium-
calcium counter-transport and sodium-hydrogen counter-transport.
• Sodium-calcium counter-transport occurs through all or almost all
cell membranes, with sodium ions moving to the interior and calcium
ions to the exterior.
• Sodium-hydrogen counter-transport occurs in several tissues. An
especially important example is in the proximal tubules of the
kidneys, where sodium ions move from the lumen of the tubule to the
interior of the tubular cell, while hydrogen ions are counter-
transported into the tubule lumen.
• As a mechanism for concentrating hydrogen ions, counter-transport is
not nearly as powerful as the primary active transport of hydrogen
ions that occurs in the more distal renal tubules, but it can transport
extremely large numbers of hydrogen ions, thus making it a key to
hydrogen ion control in the body fluids 72
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73. Active Transport Through Cellular
Sheets(Transcytosis)
• At many places in the body, substances are transported all the
way through a cellular sheet instead of simply through the
cell membrane.
• Transport of this type occurs through the:
– intestinal epithelium
– epithelium of the renal tubules,
– epithelium of all exocrine glands
– epithelium of the gallbladder, and
– membrane of the choroid plexus of the brain and other
membranes.
• The basic mechanism for transport of a substance through a
cellular sheet is
(1) active transport through the cell membrane on one side of
the transporting cells in the sheet, and then
(2) either simple diffusion or facilitated diffusion through the
membrane on the opposite side of the cell.
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74. 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.
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75. 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
b. Phagocytosis 75
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76. 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 autocrine signaling. 76
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