General Introduction

&
Cell Physiology

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Introduction to Human Physiology
• What is Physiology?
Physiology is refers to the study of the normal function
of the living structures.
The human physiology is concerned with the way the
various systems of the body functions & the way each
contributes to the functions of the body.
In other words, human physiology is concerned with
specific characteristics & mechanisms of the human
body that make it a living being & the mechanisms which
help in the adaption & homeostasis.

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Introduction, cont’d
• Historical background: Physiology is an experimental
science to which a number of scientists contributed a lot:
 William Harvey in 1628:
He correctly described the direction of blood circulation.
 Claud Bernard, a French physiologist in 19th C:
Described that every cell in the body is bathed with fluid
environment called extra cellular fluid (ECF).
ECF contains all the needed substances for cells.
He called ECF is the “internal environment of the body”
 Walter cannon:
Another physiologist, in 19th century, termed maintenance
of the constant conditions in the ECF as homeostasis.

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Introduction, cont’d
• Fields of Physiology
Each type of life, from simple virus to complicated human
being, has its own functional characteristics.
Therefore, the field of physiology can be divided into:
─Viral physiology,
─Bacterial physiology,
─Cellular physiology,
─Plant physiology,
─Human physiology, &
 Subdivisions: CVS, Renal, RS, CNS physiology, etc.
• Goal of Physiology
─ To explain the physical & chemical factors that are responsible
for the origin, development & progression of life.

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Introduction, cont’d
• Relationship b/n physiology & other sciences
Physiology has a strong link with other disciplines, such as
 Anatomy
 Biochemistry
 Pathology
 Pharmacology &
 Physics
• Physiology as a quantitative science
All physiological parameters are expressed in numbers & units.
E.g:- Blood pressure, blood glucose level & body temperature.

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 Homeostasis
• The maintenance of relatively constant or steady-state of the
internal conditions is referred to as homeostasis.
• In order for the body to function optimally, conditions within
the body, referred to as the internal environment, must be
very carefully regulated.
• ECF is in constant motion throughout the body. This is not to
say that the internal environment is fixed or unchanging.
• It is more accurate to say that the internal environment is in a
dynamic steady state — one that is constantly changing, but
in which optimal conditions are physiologically maintained.

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Homeostasis, cont’d
• It is important b/c the cells & tissues of the body will survive
& function efficiently only when these internal conditions
are properly maintained.
• Therefore, many important variables, such as body To, BP,
BGC, O2 & CO2 content of the blood, & electrolyte balance,
are actively maintained within narrow physiological limits.
• Essentially all organs of the body perform their functions to
maintain constant conditions in the ECF.

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 Homeostasis, cont’d
For example:

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Regulatory Systems of Homeostasis
• Two regulatory systems in the body influence the activity of
all the other organ systems so that maintain homeostasis:
– Nervous system (NS) and
– Endocrine system (ES)
• They are control & regulatory bodies of the homeostasis.
• In general,
– nervous system primarily regulates muscular activity &
glandular secretion and
– endocrine system primarily regulates metabolic activity in the
body’s cells.
– However, these two systems may work together in the regulation of
many organs, as well as influence each other’s activity. 9
 Regulatory Systems, cont’d
1. Nervous regulatory mechanism
• The nervous system has 3 major components: sensory,
integrative & motor portions.
a) Sensory portion: receptors detect any changes in the
body (e.g. BGC, BT, BP, pain), & send impulse to CNS
via afferent neurons.
b) CNS: integrative portion consists brain & spinal cord.
√ Brain receives, processes, and stores sensory input;
generates thoughts; and determines appropriate response
to the input & sends impulse via motor neurons.
√ Spinal cord is important in processing reflexes.

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 NS regulatory mechanism, cont’d
√ It is within this integration area (CNS) of the NS that the actual
value of a physiological variable as measured by a sensory
receptor is compared to its set point or optimal value.
√ One or more compensatory responses are then determined.

c) Motor division: carry out the appropriate physiological

responses to the effector tissues (organs, muscles, or glands)
to bring the variable back to within its normal limits.

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 Regulatory system, cont’d
2. Hormonal regulatory mechanism
• Endocrine system is another regulatory system w/c contributes
in the maintenance of homeostasis by secreting hormones.
• Hormones are transported in the blood to specific tissues upon
which they exert their effects.
Examples
 PTH  acts on kidneys, bone, intestine [Ca2+]
 Aldosterone  acts on the kidneys, intestine [Na+]
 ADH  acts on the kidneys to promote H2O re-absorption
Therefore, these hormones control water-electrolyte balance.
 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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 Homeostatic Values
1. Body fluid volume = 42 L
 ECF = 14 L
 ICF = 28 L
2. Osmolality = 300 mosm/L (285–300 mosm/L)
3. Body T. = 36.2–37.2OC
4. pH = 7.35 – 7.45
5. Blood Gases:
 PCO2 = 35–45 mm Hg
 PO2 = 40–104 mm Hg
6. Electrolytes (ECF):
 Na+ = 142 meq/L
 K+ = 4 meq/L
 Ca2+ = 10 mg/dL or 5 meq/L
 Cl- = 103 meq/L
 HCO3- = 27 meq/L
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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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Figure. Fluid compartments of the body. Volumes are for an average
70-kg person. TBW = total body water; ECF = extracellular fluid.
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Homeostatic Values, continued
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 (PP) = SBP–DBP = 40 mm Hg
 Mean ABP = DBP + 1/3(PP) = ≈ 90 mm Hg
 Pulmonary ABP = 25/10
 Cardiac output (CO) = Blood Volume = 5 L/min
10. RBC count = 4–6 millions/mm3
11. WBC count = 4000–11,000/mm3
12. Hemoglobin (Hb) = 12–16 g/dL in F & 14–18 g/dL in M
Deviations from normal ranges = Pathology.

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 Feedback Control Mechanisms
of the Homeostasis
• The body organs receive information (feedback) about the
extent of their activities through the regulatory mechanisms
(NS or ES).
• These feedback systems alter the function of organs by
increasing or decreasing their activities.
• There are 2 types of feedback mechanisms:
A. Negative Feedback Mechanism (NFM)
B. Positive Feedback Mechanism (PFM)

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Negative Feedback Mechanism
• It works by producing an effect which opposes the previous
condition (the initiating stimulus) of the organ.
− Example: when blood CO2 level is ↑, the NFM stimulates
the respiratory center, which has an effect to ↓CO2 to the
normal level by increasing pulmonary ventilatory rate (PVR).
• In general, if some factors (parameters) become excessive or
too little, a control system initiates NFM, which consists of a
series of changes that returns the factors toward certain
mean/normal values (set point), thus maintain homeostasis.
• Most of the body’s compensatory homeostatic mechanisms
function by way of negative feedback.
Examples
(1) Control of BP (2) Control of BGL (3) Control of body temperature
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Positive Feedback Mechanism
• It works by producing an effect which enhances or repeats
the same action like that of the starting stimulus.
• Most of the action of this mechanism disturbs the internal
environment, and cause disease & death.
• Example: If a person suffers from a heart attack that damages
the heart function, then the heart pumps less amount of blood
to tissues, including the heart muscle & the brain.
• If heart muscle does not get sufficient nutrients & O2, activity
of the heart becomes weaker and weaker & the weaker the
heart the lesser blood is pumped, and then death may occur.

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

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LH surge: Positive feedback mechanism

GnRH HT

Pituitary
Activates

LH

Ovary

Estrogen
>200 µg/ml
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 Levels of Organization of Human Body
• Chemical level: atoms, the smallest units of matter that
participate in chemical reactions, & molecules, two or more
atoms joined together. Certain atoms, such as carbon,
hydrogen, oxygen, nitrogen, phosphorus, calcium, & sulfur,
are essential for maintaining life. Two familiar molecules
found in the body are DNA (genetic material passed from one
generation to the next, & glucose (blood sugar).
• Cellular level: molecules combine to form cells, the basic
structural & functional units of an organism. Cells are the
smallest living units in the human body. Among the many
kinds of cells in our body are muscle cells, nerve cells &
epithelial cells.
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Structural levels of organization of human body
Muscle cells
Nerve cells
Cells: 4 types Epithelial cells
Cells in connective tissues
Muscle tissue
Tissues: 4 types Nerve tissue
Epithelial tissue
Connective tissues
Organs: e.g. Heart, lungs that are made up of 4 types of tissues.

Organ systems: e.g. Respiratory system, CVS, CNS, etc.

Organism: Human organism

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Organization of the cell (Generalized cell)

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 Generalized cell
Components of the cells:
• A typical cell that seen by the light microscope has two
major parts: Nucleus & Cytoplasm.
• Nucleus: separated from cytoplasm by nuclear membrane.
• Cytoplasm: separated from the surrounding fluid (ECF) by
plasma membrane.
• Different substances that make up the cell are collectively
called protoplasm.
• Five basic substances that composed in protoplasm are:
H2O, electrolytes, proteins, lipids, and CHO.

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Physical structure of the cell
1. Cell membrane (plasma membrane)
2. Cytoplasm & its organelles
• The cytoplasm is filled with both minute and large
dispersed particles & the organelles.
• Dispersed in the cytoplasm are dissolved proteins,
electrolytes, glucose, and cellular organelles:
endoplasmic reticulum (ER), Golgi apparatus,
mitochondria, ribosomes, and lysosomes.

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 Plasma membrane
• It is a sheet-like structure that surround (enclose) the cell,
separating cellular contents from ECF.
• Composed of proteins & lipids in a ratio of 55:42
respectively, and carbohydrates, 3%

Percentage proportion:
1. Proteins: 55%
Phospholipids = 25%
2. Lipids: 42% Cholesterol = 13%
Neutral fats = 4%
3. Carbohydrate: 3%
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Functions of the plasma membrane
1. Separates cellular contents from the ECF.
2. Regulates the passage of substances in and out. It is a semi-
permeable allowing some substances to pass thru it,
excluding others.
─ This creates unequal distribution of ions on both sides of the
membrane.
3. Provides receptors for neurotransmitters, hormones & drugs.
4. It is a means of cell-to-cell contacts.
5. Roles in the generation & transmission of electrical impulses
in the nerve & muscle cells.

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Lipid component of cell membrane
• A plasma membrane is a fluid
in its nature.
• Cell membrane consists of an
organized arrangement of ECF ICF
proteins, lipids, & CHO.
• The major lipids are
phospholipids & cholesterol.
• Lipids form the basic
structure of the membrane.
• Lipid molecules are arranged
in two parallel rows, forming
a lipid bilayer.
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Plasma membrane, continued
• The lipid component (primarily phospholipid) is organized
into a double layer with their hydrophobic (tail) directed
toward the center of the membrane & the polar heads
(hydrophilic) directed out ward facing the ECF & ICF.

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 Plasma membrane, continued
• The lipid bilayer portion of the cell membrane is impermeable to
H2O & H2O soluble substances such as ions, glucose, urea & others.
• On the other hand, fat soluble substances such as O2, CO2, alcohol
& drugs can penetrate this portion of membrane.

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Fig. Functional structure of the cell membrane
Membrane Proteins
There are 2 types of membrane proteins: integral & peripheral.
1. Integral or intrinsic proteins:
• Transmembrane proteins are integral proteins that span the
entire lipid bilayer.
• They serve as:
Channels through which ions pass.
Pumps which actively transport ions.
Carriers which actively transports materials across the
bilayer, e.g. glucose.
Receptors for neurotransmitters & hormones.
Integral proteins that are present only on one side of the
membrane, serve primarily as enzymes.
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Membrane proteins, continued
2. Peripheral or extrinsic proteins:
– They 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 glycocalyx, which cover cell membrane.

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Membrane Carbohydrates
• Attached invariably on the outside surface of membrane,
binding with protruded integral proteins & lipid, they form
glycoprotein & glycolipid (glycocalyx) respectively.

• They play a role in the

1. Immune reaction (antigenic importance).
2. Cell to cell attachment.
3. Act as receptors for NTs, hormones and drugs.

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 Nucleus
• Nucleus is the control center for cells.
• Contains genes, which are the units of heredity.
• Chemically each gene consists of highly compressed
DNA in the form of chromosomes.
• The nucleus is also the site of RNA synthesis.
• There are three kinds of RNA:
– Messenger RNA (mRNA)
– Ribosomal RNA (rRNA)
– Transfer RNA (tRNA)

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 Cellular Organelles
• Embedded within the cytoplasm are organelles or inner
organs of the cell.
• These include the ribosomes, endoplasmic reticulum (ER),
Golgi apparatus, mitochondria, lysosomes, and the
cytoskeletal system (microtubules & microfilaments).

• Ribosomes
– are the site of protein synthesis in the cells.
– small particles composed of rRNA & proteins.
– found in two forms: attached to the wall of ER or as
free ribosomes.
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Endoplasmic Reticulum (ER)
• An extensive membranous structure that connects various
parts of the inner cell.
• ER is also connected to the nuclear membrane.
• Two types of ER are: rough ER & smooth ER.
– rER is studded with ribosomes
– rER is the site of protein synthesis
– sER is free of ribosomes.
– Function of the sER varies in different cells.
– Sarcoplasmic reticulum (SR) of skeletal & cardiac muscle
cells are forms of sER.

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ER, continued
• Calcium ions needed for muscle
contraction are stored & released
from SR of muscle cells.
• In liver, sER involves in storage
of glycogen & drug metabolism.
• ER can synthesize a group of
drug metabolizing enzymes
called microsomal system.
• Functions of sER:
1. Glycogen storage
2. Calcium storage
3. Lipid biosynthesis
4. Drug metabolism Endoplasmic reticulum (rER & sER)
(detoxification)
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Golgi Complex
• The Golgi complex
communicates with ER, and
acts as a receptacle for
hormones & other
substances that produced
from the ER.
• It then modifies & packages
these substances into the
secretary granules.

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Mitochondria
• Are the “power plants” of the cell,
capable of producing the energy
rich compound, ATP which is
required for various cellular
activities.
• They require oxygen to produce
energy (ATP) from food stuffs.

Lysosomes
• Membranous structures in the cytoplasm that contains aggregates
of enzymes. Well developed in the macrophages.
Function:
• Degrade old dead cells & phagocytosis of microorganisms.
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 Cytoskeletal system of the cell
• They are microfilament and
microtubules, rigid threadlike
structures dispersed through
out the cytoplasm.
Functions
1. Maintain shape of the cells.
2. Serve as a transport system
for movement of molecules &
organelles within the cell.
e.g. axoplasmic transport.
3. Provide for support &
movement of cilia & flagella.
4. Cell to cell contact: to fasten
cell membranes together. Microtubules organized as 9+2 doublets

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 Transport through the cell membrane
• Substances are
transported through the
cell membrane by: Passive
process
1. Simple diffusion
2. Facilitated diffusion
3. Osmosis ECF
4. Active transport
(1O & 2O) and
ICF
5. Vesicular transport
mechanisms.

Diffusion through the cell membrane is divided into two subtypes

called simple diffusion & facilitated diffusion.
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 Simple Diffusion
• It is a passive movement of substances down their conc. gradient.
• Factors affecting rate of diffusion:
– Lipid solubility of the substances
– Membrane permeability
– Concentration differences or pressure differences
– Electrical potential differences of ions
• Membrane permeability can be affected by:
– Membrane thickness
– Lipid solubility
– Number of ion channels per unit area
– Temp.: T  thermal motion of molecules  permeability
– MW
• E.g:- Substances that are transported by simple diffusion are CO2,
O2, alcohol, lipid soluble drugs, & ions through specific channels
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 Facilitated diffusion
• Also called carrier-mediated diffusion.
• Carriers are saturable, do not need
energy.
Glucose
• Transports substances down their conc.
gradient.
• Among most important substances that ECF
cross cell membranes by facilitated Cell membrane
diffusion are glucose & amino acids.
ICF
• Insulin can ↑ rate of facilitated diffusion
of glucose as much as 10 to 20-fold
– the principal mechanism by w/c insulin Carrier protein
controls glucose use in the body.

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 Osmosis (“Net Diffusion” of Water)
• Is the power of movement of H2O
from an area of higher amount of H2O
to an area of lower amount of H2O
through semi-permeable membrane.
• Net movement of water caused by a
concentration difference of H2O is
called osmosis.
• The direction of movement of H2O is
governed by the amount of osmotically
active particles (solutes).
• The pressure that opposes osmosis of
H2O is called osmotic pressure.
• The H2O molecules can not transverse
the lipid bilayer simply. Instead they
pass through specific H2O channels
called aquaporins. 45
 “Active Transport” of Substances
Through the Membranes
• Substances are transported “uphill” Common examples:
against concentration gradient, or 1. Na+-K+ ATPase
( “uphill” against an electrical or 2. H+-K+ ATPase
pressure gradient). 3. Ca2+ ATPase
• Used for transport of Na+, K+, Ca2+,
H+, Cl-, iodide ions, different sugars,
& most of the amino acids.
• Consumes energy in form of ATP.

Primary active transport:

- Carrier protein is involved.
- Consumes energy from ATP.
- Carrier protein is anti-porter. 46
Primary active transport: Na+-K+ ATPase
Na+-K+ Pump
• It pumps 3Na+ outward & 2K+ inward.
• It maintains Na+ outside & ↑K+ inside.
• It maintains electro-positivity outside &
electro-negativity inside.
• Na+-K+ pump is a carrier protein that is
made up of two subunits. It has 3
binding sites for Na+ inside, and 2
binding sites for K+ on the outside.
• It has ATPase activity inside.
ATP = ADP + ---P + energy.
• Energy brings conformational change of
the pump, so that, Na+ pumped outward
& K+ inward.
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 Secondary active transport
(Co-Transport & Counter-Transport)
Secondary active transport:
- Carrier protein is involved
- Consumes energy
- Carrier protein is symporter
Examples
1. Na+ co-transport of glucose &
amino acids.
2. Na+ counter-transport of Ca2+
& H+ Ions.
Uniport carriers: Carry a single substance to one direction
Antiport carriers: Carry two substances in the opposite directions
Symport carriers: Carry two substances into the same direction 48
Vesicular transport
Substance to be endocytosed
 There are two types:

1. Endocytosis:- two forms:

a. Pinocytosis
- taking in of the fluid substances
b. Phagocytosis
- taking in of the solid particles

2. Exocytosis
- removal of substances out of cell

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