INTRODUCTION TO GENERAL embryo through larva or fetus

PHYSIOLOGY to adulthood
 Cell Physiology
Physiology o vital information on the
 Study of the biological functions of physiology of the cells
organs and their interrelationships themselves, which can be used
 Studies interplay of factors that affect to understand the physiological
growth (connectedness of each aspect of responses of tissues, organs,
the body) and organ systems
 Studies how the smallest (genes, cells)
up to the largest (organ, organ system) Physiological Differences
function in order to sustain life. PLANTS ANIMALS
 Structure + Function Mostly producers Consumers
Unlimited scheme of Limited
Physiology is an Integrating Science growth
 Brings together everything known about Non-motile and must Can move around
an animal’s function to create an integral rely on immediate
picture of how an animal operates in its nutrient sources
environment Use large amounts of Give off CO2
O2
Diversity is the hallmark of physiology. Conserve nitrogen Give off nitrogen as
 meeting the demands of survival has waste
resulted in numerous evolutionary Transports Bloodstream
variations on the basic theme of life fluids/foods through
vascular tissues
Unifying Themes of Physiological Processes Grow throughout their Reaches a certain
 obey physical and chemical laws entire lifetime stage and growth
 regulated to maintain internal conditions more or less stops
and trigger and appropriate response
 physiological state of an animal is part
 Claude Bernard (1813 – 1878)
of its phenotype, which arises as the
o French physiologist
product of the genetic make-up or
o Father of modern physiology
genotype, and its interaction with the
environment. Observation:
Internal environment remains remarkably
Sub-disciplines of Physiology constant despite changing conditions in the
 Comparative Physiology external environment.
o Species are compared in order (homeostasis – regulating the body)
 Walter Cannon (1871 – 1945)
to discern physiological and
o American Physiologist
environmental patterns
 Environment Physiology o 1932: coined the term homeostasis to
o Examines organisms in the describe this stable internal
context of the environments environment.
they inhabit (evolutionary
adaptations) Two Themes of Physiology
 Evolutionary Physiology 1) Integration
o techniques of evolutionary 2) Homeostasis
biology and systematics are
INTEGRATION
used to understand the
 Integrative physiology
evolution of organisms from
 32nd Congress of the International Union
physiological viewpoint,
of Physiological Sciences in Glasgow,
focusing on physiological
Scotland (August 1 – 6, 1993)
markers rather than anatomic
 Research levels from whole body
markers
(genes, organelles, cells, tissues, organs)
 Developmental Physiology
 At present, from gene to function
o how physiological processes
unfold during the course of
Organ systems don’t work alone.
organism development from
 Respiratory system takes in oxygen
and removes waste gases
  Cardiovascular system is  Lymphatic
responsible for delivering the  Respiratory
oxygen to all parts of our bodies  Digestive
o Organ System  Urinary
Interrelationships  Reproductive
 Nutrients and oxygen  Nervous
are distributed by the  Endocrine
blood
 Metabolic wastes are Central Themes in Physiology
eliminated by the 1. Structure/Function Relationships
urinary and respiratory o Function is based on structure
systems o Form fits function at all the
Biological Hierarchy levels of life, from molecules to
organisms
o Knowledge of a structure
provides insight into what it
does and how it works,
knowing the function of a
structure provides insight about
its construction
o biological function at each level
of organization depends on the
structure of that level and the
levels below

Example:
Aerodynamic efficiency in the
shape of bird wing
 A honeycomb internal
structure produces light but
strong bones.
 flight muscles are
controlled by neurons that
transmit signals between
Four Tissue Types the wings and brain
o Connective tissues  Ample mitochondria
o Binds together or supports provide the energy to
power flight
cells, other tissues/organs
(skeletal system)
2. Adaptation, Acclimatization, and
o Muscle (Contractile) tissues
Acclimation
o Contracts on stimulation,
o Physiology of an organism is
movement, posture and heat
very well matched to the
production (heart)
environment it occupies,
o Nerve tissues
thereby ensuring its survival
o Conducts nerve impulses
throughout the body Adaptation
o Epithelial tissues o evolution through natural
o covers all body surfaces; lines selection leading to an organism
all cavities; forms glands whose physiology, anatomy, and
o protective barrier against the behavior are matched to the
environment demands of its environment;
generally irreversible
Organ and Organ Systems o a physiological process is
Major Organ Systems adaptive- present at high
 Integumentary frequency in the population
 Skeletal because it results in a higher
 Muscular probability of survival and
 Circulatory
 reproduction than alternative 1. Dynamic equilibrium
processes 2. Inspite of multiple stimuli
o physiological and anatomic 3. Maintained by negative feedback
adaptations genetically based,
passed on from generation to  The ability to maintain a relatively stable
generation (DNA) and constantly internal environment in an ever-changing
shaped and maintained by natural outside world
selection o The body functions within relatively
Acclimatization narrow limits
o physiological, biochemical, or o All body systems contribute to its
anatomic change within an maintenance
individual animal during its life  The internal environment of the body is in a
that results from an animal’s dynamic state of equilibrium
chronic exposure in its native  Chemical, thermal, and neural factors
habitat to new, naturally interact to maintain homeostasis
occurring environmental
condition Homeostatic Control Mechanism
o animal in migrate to high altitude
o reversible
Acclimation
o refers to the same process as
acclimatization when the changes
are induced experimentally in the
laboratory or in the wild by an
investigator
o animal placed in hypobaric
chamber
o reversible
3. Homeostasis
o The tendency of organisms to
regulate and maintain relative
internal stability  Regulation of homeostasis is
4. Feedback Control Systems accomplished through the nervous and
o regulatory processes that maintain endocrine systems
homeostasis in the cells and
multicellular organisms depend Basic Components of Homeostatic Control
on feedback o Receptor – detects changes (stimuli) in
 return of information to the body
a controller that o Control Center – determines a set point
regulates a controlled for a normal range
variable o Effector – causes the response
 occurs when sensory determined by control center
information about a
particular variable (e.g.
temperature, pH,
salinity) is used to
control processes in the
cells, tissues, and organs
that influence the
internal level of that
variable
5. Conformity and Regulation
o when an organism is confronted
with changes in its environment
(e.g. changes in oxygen
availability or salinity)

HOMEOSTASIS
Definitions:
 platelets. Clotting proceeds until break is sealed
by newly formed clot. (see diagram below)

FEEDBACK CONTROL SYSTEMS

Negative Feedback
o A regulatory mechanism in which a
change in a controlled variable triggers a
response that opposes the change
o Decreases or eliminates the intensity of
the stimulus (alleviate or cancel concept)
o Most homeostatic control mechanisms

Homeostatic Imbalances
o Most diseases cause
homeostatic imbalances (chills,
Positive Feedback
fever, elevated white blood
o Enhances or exaggerates the original
counts, etc.)
stimulus so that activity is accelerated o Aging reduces our ability to
o Results in change occurring in the same
maintain homeostasis – heat
direction as the original stimulus stress
o Control short in duration, infrequent o If a disturbance of homeostasis
events such as blood clotting or or the body’s normal
childbirth equilibrium is not corrected,
o Does not maintain homeostasis illness occurs
Example: o Feedback mechanisms may be
A break or tear in blood vessel wall. Clotting overwhelmed or may be not
occurs as platelets adhere to site and release functioning correctly.
chemicals. Released chemical attract more
CONFORMITY AND REGULATION
 when an organism is confronted with
changes in its environment (e.g. changes
in oxygen availability or salinity), it can
respond in one or two ways: conformity
or regulation
o conformers - environmental
challenges induce internal body
changes that simply parallel the
external conditions (unable to
maintain homeostasis)
 Osmoconformers:
shark, starfish
 Oxyconformers:
annelid worms
As value of variable in internal
environment increases, the value of variable in
external environment also increases.
o Regulators - biochemical,
physiological, behavioral, and
other mechanisms to regulate
their internal environment over
a broad range of external
environmental changes
(maintain homeostasis)
 Osmoregulators:
maintain ion
concentrations of body
CELL MEMBRANE STRUCTURE
fluids above
environmental levels
The Gateway to the Cell
when placed in dilute
water vice versa
The formation of the cell membrane defined the
 Osmoregulation: cell from the external environment. (making it
based largely on
distinct)
controlled movement
o Polymerization of pre-cursors:
of solutes between
nucleosides (sugar and base only),
internal fluids and the
phosphorylation (addition of phosphate)
external environment
o Formation of vesicle which traps the
Zone of stability is established where
homeostasis is maintained. material inside
 electron microscopy
“Requirements” on Becoming a Real Cell (inaccurate)
1. Protection
2. Set Boundaries
3. Maintain Homeostasis

Cell Membrane/Plasma Membrane

o Acts as a boundary
o Controls what enters and leaves cell
o Regulates chemical composition
o Maintain homeostasis

 It is flexible and it can contort its

structure, and allows a unicellular
organism to move.
 Studies of red blood cell plasma
membrane provided the first evidence
that biological membranes consist of 3. Fluid Mosaic Model
lipid bilayers.  Singer and Nicolson
 Phospholipid bilayer with
Plasma Membrane Models proteins partially or fully
embedded, electron
1. Sandwich Model micrographs of freeze-fractured
 Danielli and Davson membrane
 2 layers of globular proteins
with phospholipid inside to
make a layer and then join 2
layers together to make a
channel for molecules to pass

2. Unit Membrane Model

 Robertson
 Outer layer of protein with
Steps in assessing the cell membrane
phospholipid bilayer inside.
 Rapidly freeze specimen
 Believed all cells same
 Use special knife to cut membrane in
composition.
half
 Does not explain how some
 Apply carbon + platinum coating to the
molecules pass through or the
surface
use of proteins with nonpolar
 Use scanning electron microscope to see
parts-used transmission
the surface
The electron micrograph revealed that the Fluid o proteins form a collage that differs on
Mosaic Model is the most accurate and the basic either side of membrane and from cell to
paradigm of biological membrane structure. cell (greater than 50 types of proteins)
o proteins span the membrane with
hydrophilic portions facing out and
hydrophobic portions facing in.
o mosaic pattern produced by scattered
protein molecules when membrane is
viewed from above.

 The lipids in a membrane are organized

into a liquid crystalline lattice.
 The lattice becomes a frozen crystalline
gel at transition temperature.
Formation of sphere is energetically favorable.
Importance of the Bilayers of Lipids
o Having lipids in the plasma membrane
means that at least a portion of the
membrane repels the water that
constantly surrounds it. Allowing too
much water inside the cell cause the cell
to burst.

Fluid – Mosaic Model

Fluid
o plasma membrane has consistency of
olive oil at body temperature, due to
unsaturated phospholipids.
o phospholipids and proteins move around
freely within the layer, like it’s a liquid.
Mosaic
A Scheme to Study a Membrane Protein
 Solubilization, Purification, and
Reconstitution in Liposomes
 Membrane proteins can be solubilized
by detergents that disrupt the membrane

Structure of Plasma Membrane

Membrane Movement and Cholesterol
 Major membrane component in animal
a) Movement of Phospholipids cells
 Most of the lipids and some proteins  Cholesterol is not found in plant
drift laterally on either side. membranes
 Phospholipids do not switch from one  Sterols perform the
layer to the next. same function
 The lipids and proteins in the cell  Same molar amounts as phospholipids
membrane are not fixed in position but
constantly moving.

Lateral Diffusion
o Proteins move laterally within the cell
membrane

Flip-flop Diffusion
o The lipids can move both laterally and
rotate 360 degrees

b) Movement of Cholesterol

Cholesterol affects fluidity.

o At body temperature it lessens fluidity
by restraining the movement of
phospholipids; also reduce permeability
to small molecules.
o At colder temperature it maintains
fluidity by not allowing phospholipids to
pack close together.

Cholesterol in Lipid Bilayer

 The planar rings of cholesterol make the
membrane more rigid, less permeable,
and resistant to low temperature
crystallization.
 3. Enzymatic Proteins
 Carry out enzymatic reactions
right at the membrane when a
substrate binds to the active site

4. Cell Recognition Proteins

 Glycoproteins (and glycolipids)
THE MEMBRANE PROTEINS on extracellular surface serve as
ID tags (which species, type of
Classifications: cell, individual).
 Peripheral Membrane Proteins o Carbohydrates are
- proteins that dissociate from the
short branched chains
membrane following treatments
of less than 15 sugars
with polar reagents that do not
disrupt the phospholipid
bilayer.
 Integral Membrane Proteins
- can be released only by
treatments that disrupt the
phospholipid bilayer.
 Transmembrane Proteins
- span the lipid bilayer with
5. Attachment Proteins
portions exposed on both sides
 Attach to cytoskeleton (to
of the membrane.
maintain cell shape and
stabilize proteins) and/or the
Types of Membrane Proteins
extracellular matrix (integrins
connect to both).
1. Transport Proteins
 Extracellular Matrix – protein
a. Channel Proteins – for lipid
fibers and carbohydrates
insoluble molecules and ions to
secreted by cells and fill the
pass freely through
spaces between cells and
b. Carrier Proteins – bind to a
supports cells in a tissue.
substance and carry it across
 Extracellular matrix can
membrane, change shape in
influence activity inside the cell
process
and coordinate the behavior of
all the cells in a tissue.
2.

Receptor Proteins
 bind to chemical messengers
(hormones) which sends a
message into the cell causing a
cellular reaction
6. Intercellular Junction Proteins
 Binds cells together
 Tight junctions
 Gap junctions
Types of Cell Junctions

a. Tight Junction
 Transmembrane Proteins of
opposite cells attach in a tight
zipper-like fashion
 No leakage Ex. Intestine,
Kidneys, Epithelium of skin b. Gap Junction
 Bar the movement of dissolved  Channel proteins of opposite cells
materials from the lumen join together providing channels for
through the space between ions, sugars, amino acids, and other
epithelial cells small molecules to pass
 No intercellular space  Allows communication between
 Long rows of tight-junction cells.
form a complex meshwork ex: Heart muscle, animal embryos

In plants:

Experiment on Mobility of Membrane Proteins

Desmosomes
 Cytoplasmic plaques of two
cells bind with the aid of
intermediate filaments of
keratin
 Allows for stretching
ex: stomach, bladder, heart
 Permeability of the Plasma Membrane
 Many membrane proteins move freely in
the plane of the membrane Differentially (selectively) Permeability
 Not all membrane proteins have this o Allows some materials to pass
freedom of motion  Water, oxygen, carbon dioxide
o Prevents others from passing
 Proteins, carbohydrates

Factors that determine how a substance may be

transported across a plasma membrane:
 Size
 Polar or nonpolar
 Charge

PASSIVE DIFFUSION

2nd Law of Thermodynamics – governs biological

system; universe tends towards disorder (entropy)

Movement from high to low concentration

 Only small , relatively hydrophobic

molecules are able to diffuse across a
phospholipid bilayer at significant rates
by using passive diffusion
 Molecules have to dissolve in lipid
Fluorescence Recovery After Photobleaching interior
(FRAP) o Gases (oxygen, carbon dioxide)
 Can establish the rate of membrane o Water molecules (rate slow due
component movement to polarity)
o Lipids (steroid hormones)
o Lipid soluble molecules
(hydrocarbons, alcohols, some
vitamins)
o Small noncharged molecules
(NH3)
Why is diffusion important to cells and humans?
 It is important for: cell respiration, alveoli
of the lungs, capillaries, red blood cells,
medications: time-release capsules.

CELL MEMBRANE TRANSPORT

The transport of materials across the plasma

membrane
 Cell membrane is the boundary between
inside & outside
 Separates cell from its environment

Diffusion across cell membrane

Can it be an impenetrable boundary? NO
What goes in?
 Foods: carbohydrates, sugars, proteins,
amino acids, lipids, salts, oxygen, water

What goes out?

 Waste: NH4, salts, CO2 & H2O products
 o The passage of materials is aided both
by a concentration gradient and by a
transport protein.

o Facilitated diffusion is rate limited, by

the number of proteins channels/carriers
present in the membrane.

The Special Case of Water

FACILITATED DIFFUSION  Movement of water across the cell
 Diffusion through protein channels membrane
which do not interact with hydrophobic
interior Aquaporin
 Ions (Na+, K+, Cl-), Sugars (Glucose),  Water channels
Amino Acids, small water soluble o Provide corridors allowing
molecules, Water (faster rate) water molecules to cross the
o For biological molecules membrane
unable to dissolve in  Protein pores used during osmosis
hydrophobic interior  Allow for fast transport
o no energy needed
 Make possible massive amounts of
diffusion

Osmosis
 the diffusion of water across a
differentially permeable membrane
 Osmotic pressure is the pressure that
develops in a system due to osmosis

Concentration of Water
 Direction of osmosis is determined by
comparing total solute concentrations

 Hypertonic – more solute, less water

 Hypotonic – less solute, more water
 Isotonic – equal solute & water
Managing Water Balance Why is osmosis important to cells and humans?
 Cell survival depends on balancing  Cells remove water produced by cell
water uptake & loss respiration.
 Large intestine cells transport water to
bloodstream
 Kidney cells form urine

Diffusion of Non-lipid Soluble Substances

 Non-lipid soluble substances diffuse
through membrane channels
 Passively diffuse down their
electrochemical gradient through
channels that cross the lipid bilayer;
some channels are open all the time
whereas others are gated
 Membrane potential (voltage)
regulates the opening/closing of the
channel.

GATED CHANNELS
 open or close depending on the presence
or absence of a physical or chemical
stimulus.
 Example: Neurotransmitters
bind to specific gated channels
on the receiving neuron, these
channels open;
 this allows sodium ions into a
nerve cell;
 when the neurotransmitters are
not present, the channels are
closed

OVERVIEW

Porins – permit the free passage of ions and small

polar molecules through the outer membranes of
bacteria

 Hypotonic Ion Channels – mediate the passage of ions

 a cell in fresh water across plasma membranes
 Paramecium
 Gains water, can swell & Ligand-gated Channels – open in response to the
burst since it continually binding of neurotransmitters or other signaling
enters the cell molecules
 Solution: contractile
vacuole that pumps water Voltage-gated Channels – open in response to
out of the cell (ATP changes in electric potential across the plasma
driven) membrane
 Plant cells are turgid
 Hypertonic
 a cell in salt water VOLTAGE-GATED CHANNELS
 shellfish ex: membrane potential: regulates
 lose water & die opening/closing of the channel
 Solution: take up water or a. K+ voltage-gated channels
pump out salt  exist as either open or close
 Plant cells undergo depending on the membrane
plasmolysis (wilt) voltage
 has only an activation gate
 b. Na+ voltage-gated channels
 opens when the membrane Importance of Active Transport
potential depolarizes (i.e.  Bring in essential molecules: ions, amino
becomes more positive) acids, glucose, nucleotides
 has activation and inactivation  Rid cell of unwanted molecules (Ex.
gates sodium from urine in kidneys)
 Maintain internal conditions different from
the environment
 Regulate the volume of cells by controlling
osmotic potential
 Control cellular pH
 Re-establish concentration gradients to run
facilitated diffusion. (Ex. Sodium,
Potassium pump and Proton pumps)

Model of the operation of a G protein-linked

receptor

 3 Sodium ions move out of the cell and

then 2 Potassium ions move into the
cell.
 Driven by the splitting of ATP to
provide energy and conformational
change to proteins by adding and then
taking away a phosphate group
 Driven by the splitting of ATP to
provide energy and conformational
change to proteins by adding and then
taking away a phosphate group

ACTIVE TRANSPORT
 Cells may need to move molecules against Active Transport can be classified into 2
concentration gradient groups;
 shape change transports solute 1. Primary Active Transport
from one side of membrane to  Cellular energy (ATP) is directly
other used to move substances across the
 protein “pump” membrane against its concentration
 “costs” energy = ATP gradient
  The epithelial cells lining the intestine
provide a good example of active
transport drive by the Na+ gradient

Secondary Active Transport

a. Symporter
- Two substances are transported in the
same direction across a plasma
membrane.
- One of the substance moves passively
down its concentration gradient while
the second substance uses ATP to move
against its concentration gradient across
the plasma membrane
2. Secondary Active Transport
 Example:
- Substance S is actively transported out of
the cell through one channel
- Substance X moves down its concentration
gradient through 2nd channel (passive
transport) back into the cell
- Also through the 2nd channel, the energy
harnessed from the transport of Substance
X is used to move Substance S against its b. Antiporter
concentration gradient (active transport) - Two substances are transported across the
into the cell. membrane in opposite directions across
the plasma membrane
- One of the substance moves passively
down its concentration gradient while
the second substance uses ATP to move
against its concentration gradient across
the plasma membrane

Active Transport Driven by ATP Hydrolysis

 a process in which energy is provided by
another coupled reaction, is used to
drive the uphill transport of molecules in
the energetically unfavorable direction
 Ion pumps responsible for maintaining
gradients of ions across the plasma
membrane, provide important examples

Active Transport Driven by Ion Gradients

 Some molecules are transported against Active Transport Driven by Ion Gradients
their concentration gradients using  Uniport can transport only in a single
energy derived not from ATP molecule using the facilitated diffusion
hydrolysis, but from the coupled of glucose
transport of a second molecule in the  Antiport uses active transport to move
energetically favorable direction two molecules in opposite directions
  Most common form of
endocytosis
 Cell forms an invagination
 Materials dissolve in water to
be brought into cell
 Examples: intestinal cells,
kidney cells, plant root cells

VESICLE FORMATION Receptor-Mediated – ligand-receptor

- Moving things out complexes trigger infolding of a clathrin
- Transport of large molecules pit that forms a vesicle containing ligands
- Requires energy such as LDLs, some vitamins, certain
- Keeps the macromolecule contained hormones, and antibodies

I. Exocytosis
o vesicles form as a way to transport
molecules out of a cell
o Substances transported:
neurotransmitters, hormones,  Movement of very specific
digestive enzymes molecules into the cell with the
use of vesicles coated with the
Exocytosis of Proteins protein clathrin
 Coated pits are specific locations
coated with clathrin and
receptors. When specific
molecules (ligands) bind to the
receptors, then this stimulates the
molecules to be engulfed into a
coated vesicle
 Some integral proteins have
receptors on their surface to
recognize & take in hormones
cholesterol, etc.
 Example: uptake of cholesterol
This is how many hormones are secreted and how (LDL) by animal cells
nerve cells communicate with one another.

II. Endocytosis
o Vesicles form as a way to transport
molecules into a cell

Phagocytosis – large, particulate matter

(bacteria, viruses, aged or dead cells), aka
“cell eating”

Pinocytosis – liquids and small particles

dissolved in liquid, aka “cell drinking”
  provides a mechanism for the selective complexes are removed from the plasma
uptake of specific macromolecules membrane, thereby terminating the
 Clathrin-coated pits are specialized response of the cell to growth factor
regions of the plasma membrane where stimulation
specific cell surface receptors are found  Phagolysosomes, which are
o Clathrin assembles into a phagosomes fused to lysosomes, contain
basketlike structure that lysosomal acid hydrolases that digest the
distorts the membrane, forming ingested material.
invaginated pits  The ingestion of large particles by
o Clathrin molecules are not phagocytosis plays distinct roles in
really needed, they are only different kinds of cells
used for recognition
o Clathrin coated pits are
highly specific
o Clathrin coated pits occupy
about 1-2% of the surface area
of plasma membranes

 Dynamin, a membrane associated GTP-

binding protein, assists in the budding
off of pits from the plasma membrane

Protein Trafficking in Endocytosis

 Endosomes are vesicles with tubular
extensions, located at the periphery of
the cell, that fuse with clathrin-coated
vesicles which have shed their coats
 Important feature of early endosomes:
maintain an acidic internal pH as the
result of the action of a membrane H+
pump.

 Recycling to the plasma membrane is

the major fate of membrane proteins
taken up by receptor mediated
endocytosis.
 Ligands and membrane proteins
destined for degradation in lysosomes
are transported from early endosomes to j
late endosomes, which are located near
the nucleus
 Receptor down-regulation is a
phenomenon where receptor-ligand