1. Simple Diffusion

ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
Human Physiology Introduction and Homeostasis
Physiology - science that describes how
changing environments.
the bodyfunction and survive in continually
Levels of Organization:
 CHEMICAL LEVEL -includes all chemical substances (atoms, ions& molecules) necessary
for life.
 CELLULAR LEVEL - cells are the basic structural and functional units of the human
body,there are many different types of cells
(e.g., muscle, nerve, blood, etc..).
 TISSUE LEVEL - a tissue is a group of cells that
perform a specific function and the basic types
of tissues in the human body include epithelial,
muscle,
nervousand
connective
tissues.{Glands(Endocrine &Exocrine)-derived
from epithelial tissue, specialized for secretion}.
 ORGAN LEVEL - an organ consists of 2 or more
tissues that perform a particular function (e.g.; heart, liver, stomach)
 SYSTEM LEVEL - an association of organs that have a common function; there are 11
major systems in the human body, including;digestive, nervous, endocrine, circulatory,
respiratory, urinary, reproductive, muscular, lymphatic, skeletal, and integumentary.
Body Composition:
In the average young adult male, 18% of the body weight is protein and related
substances, 7% mineral and 15% fat. The remaining 60% is water.
THE INTERNAL ENVIRONMENT:
The body fluids are divided into two major functional compartments:
1. The fluid inside cells, is the intracellular fluid (ICF)compartment.
2. The fluid outside cells is the extracellular fluid (ECF) compartment, which is
subdivided into the interstitial fluid and the blood plasma.
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
The concept of an internal environment in the body correlates with the interstitial fluid
bathing cells. There is free
exchange of water and small solutes
in the ECF between interstitial fluid
and plasma across the blood
capillaries. In contrast,the exchange
of
most
substances
between
interstitial fluid and intracellular fluid
is highly regulated and occurs across
plasma cell membranes.
The volume of total body water is
approximately 60% of body weight
in men and 50% in women.
About 60% of total bodywater is ICF
and 40% is ECF. Approximately 80% of ECF isinterstitial fluid and the remaining 20% is blood
plasma, whichis contained inside the vascular system.
The basic compositions of body fluids; ECF is high in NaCl and lowin K+, whereas ICF is high
in K+and low in NaCl. Interstitialfluid is similar in composition to plasma, except that
interstitialfluid has almost no protein.
Osmolarity is the same in allcompartments.
I. Overview of Cell
A. Cells that make up human body are microscopic
B. Cells that make up a hummingbird, human, and an elephant are all
about the same size. Larger species have more cells.
C. Cells are complex, highly organized, compartmentalized structure
II. Cell Structure
A. 3 major subdivisions:
1. Plasma membrane; thin membrane composed mostly of lipids and proteins that
separates cell’s contents from its surroundings
 Physical barrier
 Its proteins selectively control movement of molecules between intracellular
fluid ICF and extracellular fluid ECF .
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
2. Nucleus
 Typically largest single cell component
 Surrounded by nuclear envelope perforated by nuclear pores
 Control center of cell
 Contains DNA; genetic material that:
1) directs protein synthesis
2) serves as genetic draft during cell replication
3. Cytoplasm
Portion of interior of cell not occupied by nucleus, Contains:
1) Cytoskeleton; interconnected system of protein fibers and tubes (microtubules,
microfilaments, intermediate filaments)extends throughout the cytosol, gives cell shape,
framework,regulates various movements.
2)Cytosol; intracellular fluid (ICF); semiliquid, gel-like mass
3) Organelles; structures suspended in ICF; each has specific role and work in integrated
manner. Most cells have 6organelles types:
 Endoplasmic reticulum (ER); series of membranes that contain protein-and
lipid-manufacturing factories(ribosomes;produce proteins)
 Golgi complex;raw proteins are processed, sorted, packaged, and directed to
proper destination
 Lysosomes;contain powerful enzymes that break down organic molecules,
vary in size and shape depending on what they are digesting.
-Average cell has about 300 lysosomes
-Digest extracellular material brought into cell
-Remove worn out organelles (Autophagy,Apoptosis)
 Peroxisomes;house oxidative enzymes that degrade toxic wastes produced
with cell or toxins that have entered cell (such as alcohol)
 Mitochondria;powerhouse of cell;extract energy from food nutrients and
transform it into usable form for cellular activities: Adenosine triphosphate
(ATP).
-Number varies widely depending on cell’s energy requirements
 Ribosomes;make proteins by translating ribonucleic acid (RNA) into chains
of amino acids in sequence controlled bydeoxyribonucleic acid(DNA)-exist free
in cytosol or attached to rough ER
 Vaults;first identified in 1990’s;may serve as cellular transport vehicles/may
play undesirable role in multidrug resistance displayed by some cancer cells
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
Cell Membrane or Plasma Membrane
I. Functions &Structure
A. General Functions:
1. Physical Isolation
2. supporting and hold the cytoplasm
3. Transport:Helps determine cell’s composition by selectively permitting certain
substances to pass between cell and its environment(selective barrier).
4. Structural-participates; in joining of cells to form tissues& organs.
5. Recognition;Plays key role in enabling cell to respond to changes in cell’s
environment(The immune response; is the ability to distinguish between self
and nonself,everybody cell carries distinctive molecules that distinguish it as
"self"). Normally the body's defenses do not attack tissues that carry a self
marker.Rather, immune cells coexist peaceably with other body cells in a state
known as self-tolerance.
B. Basic Structure
1. Fluid phospholipid bilayer embedded with proteins
 Phospholipids have a polar (electrically-charged) head and two nonpolar
(electrically neutral) fatty acid tails
 Polar heads are hydrophilic(water-loving);can interact with water molecules
 Nonpolar tails are hydrophobic (water-fearing);will not mix with water
 Hydrophilic heads line up on both sides in
contact with water (outer surface is exposed to
ECF and inner surface is in contact with ICF)
 Tails hidden in center away from water
 Cholesterol inserted in between phospholipids molecules it contributes to fluidity,
stability
cholestrol
2. Membrane carbohydrates;(glycoproteins,
glycolipids)small amount located only at outer
surface.
3. Membrane Proteins;attached to or inserted
within lipid bilayer. Anatomically, 2 groups:
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
a. Peripheral;attach loosely to other proteins that span the membrane or to lipid bilayer
b. Integral;tightly bound into the phospholipid bilayer.
•Transmembrane Proteins;integral proteins that extend all the way through the membrane.
Many of the proteins associated with the plasma membrane are tightly bound to it.


Proteins that penetrate the membrane are hydrophobic.
Membrane proteins have many functions:
o receptors for hormones; Recognize and bind
with specific molecules in environment of cell;
therefore, chemical messengers in blood, such
as hormones, are able to influence only the
specific cells(those have receptors for given
messenger)
e.g.Thyroid
stimulating
hormone(TSH) can only attach to thyroid gland.
o pumps for transporting materials across the membrane
o
ion channels;
 Create water-filled passageway to enable water-soluble substances that are
small enough to enter or pass through membrane without coming into direct
contact with hydrophobic lipid interior.
 Restricted to ions and water
--May be specific for 1 ion
--May allow ions of similar size & charge to pass
--May be open or gated
o
o
Adhesion molecules for holding cells to extracellular matrix
Cell recognition antigens;Recognitionof “self glycoproteins” on surface of
membrane structural proteins;maintain shape of cell
o
Carriers or transporters(membrane transport protein):
Transfer specific substances across membrane that are unable to cross on
their own.
Bind with specific molecule and carry across membrane by changing shape.
Never form a continuous passageway between ICF and ECF,only open to one
side.
4. Some membranes have microvilli, cilia, flagella
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
II. Membrane Transport:
A. Membrane Permeability:
Permeability refers to ability of substances to enter/leave cell.
1. Permeable
2. Impermeable
3. Selectively permeable
2 properties influence whether substance can pass through unassisted:


Solubility of particle in lipid (highly lipid-soluble particles dissolve & pass through)
Size of particle
B. Two General Types of Movement Across Membrane
1. Passive;does not require input of energy (uses only energy of molecular
movement)
2. Active;requires energy (ATP) to transport substance across.
Active transport of Na+ and K+ is one of the major energy-using processes in the body. On
the average, it accounts for about 24% of the energy utilized by cells, and in neurons it
accounts for 70%. Thus, it accounts for a large part of the basal metabolism.
C.Passive Transport (unassisted)
Terms you should know:
 concentration gradient;difference in concentration of substance between two
places (sometimes called chemical gradient)
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ELL;membrane, transport, communication, homeostasis

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Dr. Saad Kleman Abd
solution
solvent
solutes
net diffusion
Types of passive transport:
1. Simple Diffusion;movement from a region of high concentration
to region of low concentration (i.e. down a concentration gradient)
 Rate of diffusion affected by (Fick’s Law of Diffusion);
a. Surface area of membrane
b. Magnitude of concentration gradient
c. Molecule size & weight
d. Temperature
e. Thickness of cell membrane
f. Lipid solubility of substance
 Ions can also permeate membrane along
electrical gradient:Electrical forces;(like
charges repel, opposite charges attract).
2. Osmosis
a. Movement of water down its concentration gradient across a selectively permeable
membrane(many cell types have aquaporins that allow passage of water)
b. Water moves by osmosis to the area of higher
solute concentration, i.e. to dilute the area.
c. As solute concentration increases, the water
concentration decreases correspondingly.
d.Osmolarity; measure of a solutions total
concentration given in terms of number of ions
(osmole/liter),normal osmolarity of body fluids is
300mOsm/L (millosmole/liter)
(Osmolarity tendency of a solution to pull water in)
osmosis often produces significant volume changes,
causing swelling or shrinking;
a)
b)
c)
If the external solution balances the osmotic pressure of the cytoplasm it is said to
be isotonic.
If the external solution is more dilute than the cytoplasm it is hypotonic
if the external solution is more concentrated it is hypertonic.
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
Tonicity; the ability of solution to change the size and shape of the cell by altering the
amount of water they contains, it describes what would happen to cell volume if cell where
placed in the solution.
 Clinically important;IV fluids typically isotonic
 Isotonic saline (0.9% NaCL solution)
 Usually ECF is kept isotonic so not net diffusion of water occurs. Cells, esp. brain
cells do not function properly if swollen or shrunken.
 Sometimes use hypotonic or hypertonic fluids therapeutically to correct osmotic
imbalances
D.Carrier-Mediated Transport,Co-transport,or Assisted Membrane Transport;
Large, poorly lipid- soluble molecules, such as proteins, glucose, etc. cannot cross
plasma membrane on their own no matter what forces are acting on them so need the aid of
a carrier protein.
 Carrier protein spans thickness of plasma membrane
 Carrier proteins bind to specific substances and transport them by changing
shape.
 Carriermediated Transport, demonstrates 3 properties:
1) Specificity
2) Competition
3) Saturation
 2 forms of carrier-mediated transport depending on whether energy must be
supplied to complete the process:
1. Facilitated Diffusion;same properties as simple diffusion but uses a carrier (Special
Proteins) to assist the transfer.
carrier
An extracellular molecule binds to the
transport protein, the transport protein
then rotates and releases the molecule
inside the cell
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ELL;membrane, transport, communication, homeostasis
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Dr. Saad Kleman Abd
Examples:
Glucose transporters that cotransport Na+ and glucose
Water channels aquaporins transport water in the kidney
Properties of facilitated diffusion:
o
o
o
o
o
Facilitated diffusioncannot cause net transport of molecules from a low to a high
concentration,as this would require input of energy
ATP energy not required
Transport rate reaches a maximum when all of the protein transporters are being
used (saturation)
It's very specific it allows cell to select substances taken up
Sensitive to inhibitors that react with protein side chains
2. Active Transport;requires energy input from ATP and moves a substance against
its concentration gradient.
Pumps; are proteins that use energy to carry substances across the cell membrane
Can transport substances from a low concentration
pump
to a high concentration ("uphill" transport)
o ATP energy required
o Examples: The Na+/K+-ATPase (known as the
“sodium pump”), Ca2+-ATPases (the Ca pump), H+/
K+-ATPases, H+-ATPases, multidrug resistance
(MDR) transporters
o Transport rate reaches a maximum when all of the
protein transporters are being used (saturation)
o Very specific, allows cell to select substances taken up
o Sensitive to inhibitors that react with protein side chains
Extremely important in physiology: about a third of your basal metabolism is used in
active transport of various substances
o
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
Secondary Active Transport:
Many Molecules Enter Cells by Secondary Active Transport
Secondary Active Transport; Combines active transport and facilitated diffusionExamples:
Glucose transport across the wall of the gut.
 Na+ gradient is produced by the Na pump (active transport)
 The Na+ concentration gradient is used to produce secondary transport of sugars
and amino acids (facilitated diffusion)
 Some sugar and amino acid transporters must bind Na as well as the sugar or
amino acid (coupled transport)
 Both Na+ and the organic molecule must be present at the same time and on
the same side of the membrane
 Since there is more Na outside the cell, sugars and amino acids get transported
mainly from the outside to the inside
 The sugar and amino acid transporters do not use ATP directly, but ATP is
required to set up the Na gradient.
There are many examples of secondary active transporters:
 Cotransporters (symporters) couple the movement of two or more solutes in
the same direction. Examples of Na+-driven cotransporters include Na+/glucose
uptake in the intestineand Na+/Cl- uptake in the kidney.
 Exchangers (antiporters) couple the movement of two solutes in the opposite
direction. Na+-driven exchangers include Na+/Ca+2and Na+/H+exchange, which
are important for maintaining low intracellular [Ca+2]and [H+], respectively.
 Mechanism of Primary Active Transport {NA+K+ Pump};
1) Most important form of active transport in cells
2) Maintains concentration gradients of NA+ and K+ across cell membrane
3) Moves 3 sodium ions from inside cell to ECF
4) Moves 2 potassium ions from ECF into cell
5) Net movement =high Na+ concentration in ECF and high K+ concentration in
ICF.
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Dr. Saad Kleman Abd
ELL;membrane, transport, communication, homeostasis
6) Transmembrane potential;inside of cell has slight negative charge as
compared to outside of cell
7)Difference in charges=a potential;reflects unequal distribution of positive and
negative charged ions.
Comparison of Simple Diffusion, Facilitated Transport & Active Transport:
Simple
Diffusion
Property
Facilitated
Transport
Active
Transport
Requires special membrane proteins
No
Yes
Yes
Highly selective
No
Yes
Yes
Transport saturates
No
Yes
Yes
Can be inhibited
No
Yes
Yes
Hormonal regulation
No
Yes
Yes
Uphill transport
No
No
Yes
Requires ATP energy
No
No
Yes
E. Bulk Transport or Vesicular Transport
 Moves macromolecules that are too large to move through channels or carriers, such
as protein hormones, bacteria ingested by white blood cells (WBCs)
 Involves moving materials in vesicles, small membranous sacs that format, or fuse
with cell membrane.
 Requires energy in the form of ATP
 Energy needed for vesicle formation and vesicle movement within cell
2 major categories:Endo& exocytosis,moving material into (endo) or out of (exo) cell in bulk
form.
Rates of endocytosis and exocytosis must be kept in balance to maintain constant membrane
surface area and cell volume.
1) Endocytosis; Movement of extracellular material into cytoplasm.Types of
1)Endocytosis:

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Pinocytosis
Phagocytosis
Receptor-mediated endocytosis
2) Exocytosis

Functional reversal of endocytosis
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ELL;membrane, transport, communication, homeostasis
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Dr. Saad Kleman Abd
Vesicle created inside cells fuses with cell membrane, then opens up and releases
its contents to the exterior
Provide mechanism for secreting large polar molecules such as hormones and
enzymes
Enables cell to add specific components to membrane such as selected carriers,
channels, or receptors depending on needs of cell
INTERCELLULAR COMMUNICATION:
Cells communicate with one another via chemical messengers. Within a given tissue, some
messengers move from cell to cell via gap junctions without entering the ECF.
In addition, cells are affected by chemical messengers secreted into the ECF. These
chemical messengers bind to protein receptors on the surface of the cell or, in some
instances, in the cytoplasm or the nucleus, triggering sequences of intracellular changes that
produce their physiologic effects.
 Three general types of intercellular communication are mediated by messengers in the
ECF:
(1) Neural communication;in which neurotransmitters are released at synaptic junctions
from nerve cells and act across a narrowsynaptic cleft on a postsynaptic cell
(2) Endocrine communication;in which hormones and growth factors reach cells via the
circulating blood
(3) Paracrine communication;in which the products of cells diffuse in the ECFto affect
neighboring cells that may be some distanceaway.
Autocrine communication; in some situations, cells secrete chemicalmessengers that bind
to receptors onthe same cell, ( the cell that secreted the messenger).
The chemical messengersinclude (amino acids, steroids, polypeptides,lipids, purine
nucleotides,and pyrimidine nucleotides).
Invarious parts of the body, the same chemical messengercan function as a neurotransmitter,
a paracrine mediator,a hormone secreted by neurons into the blood(neural hormone), and a
hormone secreted by glandcells into the blood.
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
Homeostasis
Homeostasis;body’s ability to maintain stable internal environment (internal constancy), is
essential for cell’s survival and each cell contributes to homeostasis.
Cells in multicellular environment cannot live and function without contributions from other
body cells because most of its cells are not in direct contact with external environment
System functions finally depend on specialized activities of individual cells.
Homeostatic Control Systems:
A. Networks of body components work together to maintain acontrolled variable in the
internal environment at a relatively constant set point {desired level of a variable or system
where it functions best}.
b. Classifications of Control Systems:
1.Intrinsic (local)–inherent responses of an organ to compensate for change in condition.
2.Extrinsic (systemic)–regulatory response initiated outside organ to alter organ’s activity, i.e.,
by the nervous system and endocrine system.Examples: Thyroid gland secretion,
glucose levels,….
Homeostasis regulated by:
1. Nervous System;shorter duration, more specific.
2. Endocrine System;slower to start, less specific, longer lasting. Secretes hormones
(chemical messengers) into blood, only “target organs” respond to that particular
hormone.
Homeostasis involves 3 fundamental components:
1) a receptor
2) a control center/integration center
3) an effector
Feedback Loops;feedback=responses
change has been detected
made
after
1. Negative Feedback Loop
 Widely used to maintain homeostasis
 Triggers a response that seeks to restore the
factor to normal by moving the factor in the
opposite direction of its initial change
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
 Starts with a "set point"value at which the process functions optimally (normal)
 Changes away from normal state (set point) cause reactions in opposite direction.
 Homeostatic response is turned off when response of system opposes or removes
original stimulus.
2.
Positive Feedback
*Self-amplifying cycle-output is continually enhanced of amplified so that the
controlled variable continues to be moved in the direction of the initial change.
 Does not occur in body as often as negative
 play role in certain instances, e.g., in childbirth:
 Hormone oxytocin causes powerful uterine contractions
 Contractions push baby against the cervix of mother
 Stretching of cervix triggers release of more oxytocin, causing even stronger
contractions, triggering release of more oxytocin and so on.
 Does not stop until cervix stops being stimulated (baby is born)
 Always includes a mechanism for termination of cycle
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ELL;membrane, transport, communication, homeostasis
Dr. Saad Kleman Abd
AGING
Aging affects cells and the systems made up ofthem, as well as tissue components such as
collagen,and numerous theories have been advanced to explainthe phenomenon.
 One theory of aging holds that tissues age as a result of random mutations in the DNA
of somatic cells, with consequent beginning of cumulative abnormalities.
 Others hold that cumulative abnormalities are produced by increased cross-linkage of
collagen and other proteins, possibly as the end result of the non enzymatic
combination of glucose with amino groups on these molecules.
 A third theory envisions aging as the cumulative result of damage to tissues by free
radicals formed in them. It is interesting in this regard that species with longer life
spans produce more superoxide dismutase, an enzyme that inactivates oxygen-free
radicals.
It is now established that in experimental animals, a chronically decreased caloric intake
prolongs life, and this could be true in humans as well. One possible explanation for this
effect of caloric restriction is decreased metabolism, with decreased formation of protein
cross-links and decreased production of free radicals.
However, the exact cause of the lengthened life span produced by caloric restriction remains
to be determined.
In aging humans, declines occur in the circulating levels of some sex hormones, the adrenal
androgen, dehydroepiandrosterone and its sulfate, and growth hormone.
Replacement therapy with estrogens and progesterone in women decreases the incidence of
osteoporosis.
Replacement therapy with testosterone, dehydroepiandrosterone , and growth hormone
each has some useful effects, but each also has undesirable side effects, and there is little if
any evidence that they prolong life.
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