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1.

Homeostasis

3. Describe the general characteristics and components of homeostatic


control systems.

 2 classes of homeostatic control system

o Intrinsic control (local)


 Built into or inherent in an organ
 Self-serving the organ in which they occur

o Extrinsic control
 How most factors in the internal environment are maintained
 Regulatory mechanisms initiated outside an organ to alter the
activity of the organ
 Permits synchronized regulation of several organ to commit a
goal

 Components

o Receptor
 Detects changes in the internal/external environment
 The receptor senses environmental stimuli, sending the
information to the integrating center.

o Control centre (error detector/Integrator)


 The integrating center
 brain; hypothalamus
 central command post
 pulls together information about stimuli and signals to
muscle and glands or both

o Effector
 Muscles/glands
 Carries suitable responses
 One example is the kidney, which retains water if blood pressure
is too low.
4. Differentiate between steady state and equilibrium and explain the
concept of set point regulation.

- equilibrium
o a state in which the rate of the forward reaction equals the rate of
the backward reaction

- steady state
o normal range for regulated variable
 120/80
o the stage of a chemical reaction that has a constant concentration of
an intermediate

- concept of set point regulation


o any regulated variable is regulated at a predetermined or preferred
level by feedback control mechanism

5. Differentiate between negative and positive feedback, and feedforward


regulation.

- How does homeostatic control system detect changes?

o Feedback
 Responses made after change has been detected
 Brings a reaction to change in regulated factor

o Feedforward
 Responses made in anticipation of a change
 Anticipates changes in regulated factor
 permits the body to predict a change in the physiology of the
organism and initiate a response that can reduce the movement
of a regulated variable out of its normal range
- Negative feedback
o Primary operation of homeostatic control mechanism
o Detection of a change brings about a response that reverses that
change
o Used to resist change and add stability

- Positive feedback
o Output enhances or amplifies a change so that the controlled factor
continues to move in that direction of initial change

Ex) heat generated by furnace triggers the thermostat to call for


even more heat output from furnace, increasing room temperature
EX2) occurs during child birth

For example, when a meal is still in the digestive tract, a feedforward mechanism
increases secretion of a hormone (insulin) that will promote the cellular uptake
and storage of ingested nutrients after they have been absorbed from the
digestive tract. This anticipatory response helps limit the rapid rise in nutrients
(e.g., glucose) after absorption into the blood, assisting in maintenance of a more
steady-state blood nutrient level.
2. Body fluid compartments

1. Explain the concept of body fluid compartmentalization and describe the


relevant proportions

ECF (extracellular fluid)

20~25% plasma + 75~80% Interstitial fluid (ISF)

2. Distinguish the different compositions of the ICF and ECF

ICF: high [K+], low [Na+]

ECF: high [ Na+], low [K+]


3. Movement of molecules across cell membrane

1. Define diffusion and explain the concept of diffusion equilibrium

Diffusion

- the movement of individual molecules of a substance through a


semipermeable barrier from an area of higher concentration to an area of
lower concentration
- Difference in charges between two adjacent areas produces electrical
gradient that promotes the movement of ions towards areas of opposite
charges
- At equilibrium, movement of molecules does not stop. At equilibrium, there
is equal movement of materials in both directions

How does it work?


- All molecules move  collides  scatters into lower concentration
gradient

2. What determines the magnitude of net flux across a membrane

- the greater the difference in concentration between any two regions, the


greater the magnitude of the net flux
- membrane potential

3. List the factors that determine the magnitude of solute flux

o Molecular size
 Smaller molecules diffuse faster
o Temperature
 High temp’ increases energy  faster diffusion
o Concentration
 Greater the difference in [gradient]  faster diffusion
o Medium
 viscosity
o Surface area
4. Mediated Transport Systems

1. Contrast ligan-gated, voltage-gated and mechanically gated ion


channels

(Types of transmembrane proteins)

Voltage-gated ion channel

- Open/close in response to membrane potential


- opens as a response to the voltage difference across the cell membrane
(membrane potential).
- When the electrical potential is present near the voltage gated channel, it
changes the conformation of the channel protein.
- It opens the channel across the membrane and ions enter or exit through the
passage.
- Voltage gated ion channels are ion specific
o allow permeation of only one type of ion 
- Ion specific channels
o Ex) Sodium Channels, Potassium Channels and Calcium Channels

Ligand gated ion channel

- Opens as a response to a chemical messenger (ligand) binding (ex.


neurotransmitter binding)
- less selective and allow permeation of two or more types of ions through the
channel pore

Mechanically gated ion channel


- open in response to physical deformation of the receptor, as in sensory
receptors of touch and pressure
- open in response to stretching or other mechanical deformation

2. Distinguish between diffusion, facilitated diffusion and active transport

Diffusion

- Nonpolar, lipid-soluble (hydrophobic) substances diffuse directly through


phospholipid bilayer
o E.g. oxygen, carbon dioxide, steroid hormones, fatty acids
- Small amounts of very small polar substances, such as water, can even pass

Facilitated Diffusion

- Larger, non-lipid soluble, or polar molecules can cross membrane but only
with assistance of carrier molecules

a) Carrier-mediated
o Transfer of small, water-soluble substances across the membrane

o Three characteristics that determine the kind and amount of material


transferred
 Specificity
 Each carrier transports specific substance
 Saturation
 Limited number of carrier binding sites available for a
specific substance
 Competition
 Closely related compounds compete for a ride across the
membrane on the same carrier

o Transmembrane proteins called transporters move solutes via


conformational changes.
o Three factors determine the magnitude of solute flux through a
mediated transport system
1. The extent to which the binding sites are saturated.
2. The number of transporters in the membrane.
3. The rate at which the conformational change occurs.

b) Channel-mediated
o Some integral membrane proteins form channels that allow ions to
diffuse across the membrane.
o Ion channels show selectivity for a particular type(s) of ion (for example,
Na+ and K+)
 --- based on channel diameter, charged residues lining pore,
water of hydration.

Active Transport

o Involves the use of protein carrier to transfer specific substances


against its concentration gradient across the membrane
 ATP is required to alter the affinity of the binding site when
exposed to one side of the membrane or to the other
 Binding site favors its passenger on low-concentration side due to
phosphorylation of the carrier
3. Contrast Primary and Secondary Active Transport

Primary Active Transport


(Na-K ATPase pump)

- This carrier transports sodium ions out of the cell, concentrating them in ECF
- …picks up potassium ion from outside (ECF), concentrating them in ICF
- Responsible for creation of electrochemical gradient
o direction and magnitude of ion fluxes across membranes depend on
electrochemical gradient (concentration + membrane potential)

o Creates higher [Na+], lower [K+] in ECF, higher [K+] and lower [Na+] in
ICF
 Between 10 and 40% of the ATP a cell produces under resting
conditions is used by the Na+/K+-ATPase pump to maintain the
sodium (and potassium) gradient.
Steps
i) Pump has 3 high affinity sites for Na+ and 2 low affinity sites for K+ when
exposed to ICF
ii) When 3 Na+ bind to pump, it splits ATP into ADP + phosphate group
iii) Phosphorylation causes pump to change conformations that Na+ binding
sites are exposed to ECF and are released to ECF
iv) Changes in shape exposes pump’s binding sites for K+ to ECF
v) When 2 K+ from ECF binds to pump, it releases phosphate group.
vi) Dephosrylation causes pump to revert to its original conformation
vii) 2 K+ are released to ICF

- Na-K pump moves 3 Na+ out for every 2 K+ in


Important roles of Primary Active Transport

1. Establishes Na-K concentration gradients across plasma membrane


 critically important in the ability of nerve and muscle cells to generate
electrical signals essential for their functioning

2. Helps regulate cell volume by controlling the concentration of solutes


inside the cell

3. Energy is used for the pump indirectly serves as energy source for
cotransport of glucose and amino acids across intestinal and kidney cells

Na+/K+-ATPase establishes electrochemical gradient

• The pumping activity of the Na+/K+-ATPase establishes and maintains the


characteristic distribution of high K+i and low Na+ inside and high Na+ and
low K+ outside
• Thus, the Na+/K+-ATPase establishes chemical gradients that can be used
to do work (transport of other solutes, for example).
• Between 10 and 40% of the ATP a cell produces under resting conditions
is used by the Na+/K+-ATPase pump to maintain the sodium (and
potassium) gradient.
Secondary Active Transport
(Ion coupled transport)

- Driven by electrochemical gradient


o Movement of ion down its electrochemical gradient is coupled with
transport of another molecule (i.e glucose)
 Ther’s bnding site for ion & cotransport molecule
o Electrochemical gradient depends on primary active transport

Steps

i) Cotransport carrier transfers glucose against a concentration gradient and


Na+ down a concertation gradient
ii) No energy is directly used by the cotransport carrier to move glucose
uphill. Instead, it is driven by Na+ concentration gradient established by
Na-K Pump
iii) Na-K Pump actively transports Na+ out of the cell at basolateral
membrane, keeping ICF Na+ concentration lower
iv) After entering the cell by S.A.T, glucose is transported down its
concentration gradient by facilitated diffusion
v) Na-K Pump also actively transports K+ into the cell, maintaining a high
intracellular K+ concentration
- The creation of the electrochemical gradient, however, depends on primary
active transporters.
- The energy stored in an electrochemical gradient can be used to drive the
transport of other solutes.
o Energy is required the entire process
o Not directly required to run the pump
 Rather uses second hand energy stored in forms of ion
concentration gradient to move the cotransporter molecule uphill

- In secondary active transport, the movement of an ion down its


electrochemical gradient is coupled to the transport of another molecule (ex.
Glucose, amino acids).
o Movement of Na+ into the cell by cotransport carrier is downhill
o Movement of K+ into the cell by cotransport carrier is uphill

- These transporters have binding sites for an ion (usually Na+) and the
cotransporter molecule.

o Cotransport (symport): the ion and the second solute cross the
membrane in the same direction.
o Counter transport (antiport): the ion and the second solute move in
opposite directions.

- Thus, secondary active transport uses the stored energy of an


electrochemical gradient to move both an ion and a second solute across a
membrane.
- In secondary active transport, the movement of Na+ is always downhill, from
[high] to [low].

5. Osmosis
1. Define osmolarity and differentiate between penetrating and non-
penetrating solutes

Osmolarity: total number of solute particles in a solution

• Water moves by osmosis from areas of low solute (high water) concentration
to high areas of solute (low water) concentration

• ICF and ECF is ~300 mOsm

• Na+, Cl-, K+ and proteins behave as non-penetrating solutes.

Osmosis
: driving force for movement of water across the membrane from [lower solute] to
[higher solute]

How does water permeate plasma membrane?


o Via aquaporins
 Membrane protein that forms channels used for passage of water

- Osmosis when membrane separates unequal solution of penetrating solutes


o Movement of solutes continues until both solutes and water are evenly
distributed across the membrane

- Osmosis when membrane separates unequal solution of non-penetrating


solutes
o Water from lower solute concentration mves to area with higher solute
concentration
- Osmosis when membrane separates pure water from solution of a non-
penetrating solute
o Osmosis occurs from area of pure water to area of solutes
o Concentration between the two can never equal

2. Define osmotic pressure

Osmotic pressure
o inward pressure due to tendency of water to be “pulled” into a cell with higher
osmolarities
o The more solutes inside a cell, the bigger the pull on water to enter, resulting
in higher osmotic pressures inside the cell

Hydrostatic Pressure
o outward pressure exerted on cell side of membrane caused by increases in
volume of cell due to osmosis

 Net movement of water continues until opposing hydrostatic pressure


equals osmotic pressure
 Greater [non-penetrating solutes] and lower [water], greater drive for
water to move by osmosis from pure water into the solution
 Solution with high [non-penetrating solute] exerts greater osmotic
pressure than lower [non-penetrating solute]

3. Tonicity of solutions

Tonicity
: effects a solution has on cell volume
o Whether cell remains the same size, swells, or shrinks

- Determined by its concertation of non-penetrating solutes

a) Isotonic solution (equal)


o Same concentation of non-penetrating solutes
o When cells are in isotonic solutions, no movement
 Reason why ECF is normally kept isotonic

b) Hypotonic solution (below)


o Solution with below-normal concentration of non-penetrating solutes
o Higher concentration of wter
o Lower concentration of non-penetrating solutes
o Water enters cells by osmosis

c) Hypertonic solution (above)


o Higher concentration of non-penetrating solutes
o Lower concentration of water
o Cells shrink as they lose water

6. Endocytosis and Exocytosis


1. Describe the process of endocytosis and contrast the three classes of
endocytosis. Identify the relevant molecules and organelles involved

Endocytosis
: transport into the cell

- Plasma membrane surrounds the substance to be ingested  fuses over the


surface  pinches off a membrane enclosed vesicle  engulfed material is
trapped within cell

Three forms of endocytosis


a) Pinocytosis
b) Receptor mediated endocytosis
c) Phagocytosis
a) Pinocytosis

steps
i) PM dips inward, forming a pouch that contains bits of ECF
a) Result of membrane deforming coat proteins attaching to the inner
surface of PM
ii) PM then seals at the surface of the pouch, trapping content in intercellular
endocytic vesicle
iii) Dynamin forms rings that wrap around, severing vesicle from surface
membrane
a) Proein molecule that pinches off endocytic vesicle

Roles
i. Brings ECF into cell
ii. Provides a way to retrieve extra plasma membrane that has been added to
the cell surface during exocytosis

b) Receptor mediated endocytosis

o Highly selective process that enables cells to import specific large


molecules
 Triggered by the binding of a specific molecule/protein to a surface
membrane receptor site specific for that molecule/protein
 This binding causes PM at that site to sink ink, then sealed at
the surface, trapping the protein inside the cell.

c) Phagocytosis
o Large multimolecular particles are internalized

When WBC encounters large multimolecular particle  extends


pseudopods (surrounds and engulfs large particles)  traps large particles
within an internalized vesicle  lysosome fuses with the membrane of the
internalized vesicle  releases hydrolytic enzymes in the vesicle 
enzyme largely breakdown engulfed materials into reusable ingredient
(amino acid, glucose, fatty acids)

2. Possible fates of internalized endocytic vesicles

Once inside the cell, engulfed vesicle has two destinies


i. Lysosome fuses with the vesicle to degrade and release its contents into
ICF
ii. Endocytosis bypasses lysosomes and travels to the opposite side of the
cell, where it releases its content by exocytosis

Epithelial Transport
Q Differentiate between paracellular and transcellular transport pathways

- Epithelial cells line hollow organs or tubes and tegulate the absorption or
secretin of substances across these surfaces

Paracellular
: diffusion between adjacent cells, limited by tight junction

Transcellular
: diffusion into and out of epithelial cells

Q Recognize differences in the permeability and transport characteristics of


luminal and basolateral-plasma membranes. Describe the function of tight
junctions.
- Luminal (apical) or serosal (basolateral) membranes contain different
channels and transporters which allows substances to undergo a net
movement from [low] to [high]

Q Identify the factors that affect the net movement of water across an
epithelium.

- Active transport of sodium through an epithelium increases the osmolarity


on one side of the cell and decreases it on the other, causing water to
move by osmosis in the same direction as transported sodium

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