SL TB

8/30/2023
CELLULAR PHYSIOLOGY – 1
HOMEOSTASIS & FLUID COMPARTMENTS
Giảng viên : ThS. BS. Đặng Nguyễn Tường Vân

(dntvan@medvnu.edu.vn)
Bài giảng lý thuyết trực tuyến Khoa Y – ĐHQG HCM |1
Body components
• 1 fertilized egg →
division +
differentiation
• Differentiated
cells =
specialized
function
• Tissues = groups
of cells w related
function
ThS. BS. Đặng Nguyễn Tường Vân
Khoa Y – ĐHQG - HCM
1
8/30/2023
Body components
• Organ = functional unit

• Organ system = several organs work
together to perform specific function
– Skin = barrier
– Entry = respiratory + gastrointestinal sys.
– Transport = cardiovascular sys.
– Exit = renal + GI + respiratory

Body Fluid Compartments

Total
body
water =
60%
body
weight
TBW
correlates
inversely
w body
fat
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Body Fluid Compartments

ICF = 2/3
TBW
ECF = 1/3
TBW
ISF = ¾
ECF
Plasma = ¼
ECF
ISF =
ultrafiltrate
of plasma

Male 70kg
• TBW= 60% BW = 42L
• ICF = 2/3 TBW = 28L
• ECF = 1/3 TBW = 14L
• ISF = ¾ ECF = ¼ TBW = 10.5 L
• Plasma = ¼ ECF = 1/12 TBW =
3.5L
ThS. BS. Đặng Nguyễn Tường Vân 6

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Self-regulating mechanism
1.Equilibrium: IVF & ISF
– Equal amount of substance
– No net transfer of substance or energy
– No barrier to movement
– No energy expenditure to maintain
2.Steady state: ICF & ECF
– Constant amount of substance in
compartments
– Input = output
– Require energy to maintain
What is homeostasis
• Maintanence
of ECF
constituents
as relatively
constant
• Central
theme of
physiology

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Homeostatic control & reflex

loops
• Intergration
center =
brain → set
point

Temperature reflex loops:

external change

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Temperature reflex loops:

internal change

11
Negative feedback loop

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Positive feedback loop

13
TONIC CONTROL

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ANTAGONISTIC CONTROL

15
RHYTHM
• 24h= circadian
rhythm: Cortisol, GH,
aldosterone,
testosterone
• >24h = infradian
rhythm: menstrual
cycle, thyroid
hormone increasing in
winter.
• < 24h = ultradian
rhythm: LH, prolactin.
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Khoa Y – ĐHQG - HCM | 17
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TRANSPORT ACROSS CELL MEMBRANE
part 1

Units
• amounts of solute: moles, equivalents, or
osmoles.
• concentrations of solutes: moles per liter
(mol/L), equivalents per liter (Eq/L), or osmoles
per liter (Osm/L) → millimoles per liter
(mmol/L), milliequivalents per liter (mEq/L), or
milliosmoles per liter (mOsm/L)
• 1 mole = 6.022 × 1023 molecules of a
substance. 1 millimole = 1/1000 or 10−3 moles.
• equivalent = the amount of charged (ionized)
solute
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8/30/2023
Units
• osmole = no. of particles into which a solute
dissociates in solution.
• Osmolarity = the concentration of particles
in solution = osmoles/L.
• If a solute does not dissociate in solution,
osmolarity = molarity.
• If a solute dissociates in solution, osmolarity
= molarity * no. of particles in solution

Electroneutrality of Body
Fluid Compartments
• Principle of
macroscopic
electroneutrality
• Each compartment:
mEq/L of cations =
mEq/L of anions
• Even when potential
difference across the
cell membrane, charge
balance still is
maintained in the bulk
(macroscopic) solutions

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Composition of ICF and ECF

Creation of Concentration Differences

across Cell Membranes

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Physiologic function of the

differences in composition
1. The resting membrane potential of nerve and
muscle critically depends on the difference in
concentration of [K+]
2. The upstroke of the action potential of these
same excitable cells depends on the
differences in [Na+]
3. Excitation-contraction coupling in muscle cells
depends on the differences in [Ca2+]
4. Absorption of essential nutrients depends on
the transmembrane [Na+]
Concentration Differences between

Plasma and ISF
• Plasma has Protein
• Gibbs-Donnan equilibrium: impermeant,
negatively charged proteins in plasma
require electroneutrality → plasma must
have a slightly lower concentration of
small anions (Cl−) and a slightly higher
concentration of small cations (Na+ and
K+) than ISF
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Characteristics of Cell Membranes

Fluid mosaic model of cell

membranes

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Terms
• Pump
• Transporter
=carrier
• Channel
• Leaking
channel

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Gated channels

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Gating of channels
1. Ligand = requires
binding of specific
CHEMICAl to open
2. Voltage = requires a
specific gradient of
ELECTRICAL CHARGE
across the membrane
to open
3. Mechanical = requires
specific TENSION to
open
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Importance of pumps,
transporters & channels
• Physiology processes:
- growth
- metabolic activities
- sensory
• Diseases:
- defective transporter: cystic fibrosis
- defective channel: long QT syndrome, paralysis
• Pharmacological therapies:
- hypertension: diuretics
- stomach ulcer: proton pump inhibitor
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Transport across Cell

Membranes

15
Types of mechanism

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Carrier-mediated transport
• Simple diffusion = not carrier

mediated.
• Facilitated diffusion, primary active
transport, and secondary active
transport = carrier-mediated
transport (involve integral membrane
proteins)

17
• 3 characteristics:
1. Saturation:
carrier proteins
have a limited
number of
binding sites for
the solute

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1. Saturation
2. Stereospecificity: binding sites for solute on the
transport proteins are stereospecific.
Ex: the transporter for glucose in the renal proximal
tubule recognizes and transports the natural isomer
D-glucose, but it does not recognize or transport the
unnatural isomer L-glucose

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1. Saturation
2. Stereospecificity
3. Competition: may recognize, bind, and even
transport chemically related solutes
Ex: the transporter for glucose is specific for D-
glucose, but it also recognizes and transports a
closely related sugar, D-galactose → the presence of
D-galactose inhibits the transport of D-glucose by
occupying the sites

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TRANSPORT ACROSS CELL MEMBRANE
part 2

Simple diffusion
• Random thermal
movement of
molecule across a
surface per unit
time
• Net flux is
determined by
gradient: high to
low
• Ex: urea from ECF
to ICF

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Gap junctions

Net diffusion depends on
1. Concentration gradient (C)

2. Partition coefficient (K):
solubility of a solute in oil
relative to its solubility in water
3. Diffusion coefficient (D)
4. Thickness of the membrane
5. Surface area available for
diffusion

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Facilitated diffusion

Facilitated diffusion
• Down an electrochemical potential gradient

• no input of metabolic energy
• membrane carrier
• characteristics of carrier-mediated
• GLUT4: D-glucose transport in skeletal
muscle and adipose tissue cells

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Primary active transport

• against an electrochemical potential gradient
(uphill)
• Requires metabolic energy in the form of ATP
• ATP energy source is directly coupled to the
transport process
• Ex: Na+-K+ ATPase in all cell membranes,
Ca2+ ATPase in sarcoplasmic and endoplasmic
reticulum, and H+-K+ATPase in gastric
parietal cells

Na+-K+ ATPase

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Ca2+ ATPase

H+-K+ATPase

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Secondary active transport

• the transport of 2 or more solutes is coupled:
one (usually Na+) downhill and other uphill
• metabolic energy
• ATP is supplied indirectly in the Na+
concentration gradient across the cell
membrane (The Na+-K+ ATPase, utilizing ATP,
creates and maintains this Na+ gradient)
• 2 types:
1. Cotransport (symport)
2. Countertransport (antiport, exchange)
11
Secondary active transport
• Moves more
than 1 solute
at the same
time

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Cotransport
• Same direction
• Na+-glucose
cotransport
(SGLT) and Na+-
amino acid
cotransport: in
the luminal
membranes of
the epithelial cells
of small intestine
and renal
proximal tubule
13
Cotransport
• Na+-K+-
2Cl−
cotransport
in the
luminal
membrane
of epithelial
cells of the
thick
ascending
limb

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Countertransport
• opposite
directions: Na+
into the cell,
solute out of
the cell
• Ca2+-Na+
exchange in
muscle cells

15
Countertransport
• Na+-H+
exchange
in renal
proximal
tubules

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Transcellular transporter

17

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OSMOSIS

Concentration of water

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8/30/2023
Osmosis

Osmosis
• Movement of water
• Only occurs by DIFFUSION
• Aquaporin channel = facilitated diffusion
• Highest concentration in pure water

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Osmosis
• Osmosis = the flow of water across a

semipermeable membrane because of
differences in solute concentration.
• Concentration differences of impermeant
solutes.
• Osmosis ≈ diffusion of water

Osmotic pressure
The pressure required to stop the flow of water

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Osmotic pressure
• Depends on
1. the concentration of
osmotically active
particles
2. whether the solute can
cross the membrane or
not
• van’t Hoff equation

Reflection coefficient (σ)

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Terms
Isosmotic
Hypo-
osmotic
Hyper-
osmotic

Tonicity and cell membrane

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Tonicity
• 2 solutions separated by a semipermeable
membrane have the same effective osmotic
pressure → isotonic
• 2 solutions have different effective osmotic
pressures, the solution with the lower effective
osmotic pressure is hypotonic and the solution
with the higher effective osmotic pressure is
hypertonic. Water will flow from the hypotonic
solution into the hypertonic solution.

11
Cases
Condition Total body ECF volume ICF volume ECF
water osmolarity
IV isotonic increase =
saline (NaCl)
Diarhea decrease =
(isotonic loss)
Excessive = Increase
NaCl intake
Excessive Decrease Increase
sweating
(hypotonic
loss)

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Cases
water osmolarity
IV isotonic increase ↑ = =
saline (NaCl)
Diarhea decrease =
(isotonic loss)
NaCl intake
sweating
(hypotonic
loss)

13
Cases
water osmolarity
saline (NaCl)
Diarhea decrease ↓ = =
(isotonic loss)
NaCl intake
sweating
(hypotonic
loss)

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Cases
water osmolarity
saline (NaCl)
Diarhea decrease ↓ = =
(isotonic loss)
Excessive = ↑ ↓ Increase
NaCl intake
Excessive Decrease ? ? Increase
sweating
(hypotonic
loss)

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RESTING MEMBRANE POTENTIAL

Electrochemical gradient

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8/30/2023
Equilibrium potential
1. Ion channels:
specific,
gated,
bidirectional

1. Na+ moves down

its concentration
gradient until the
electrical
gradient (+
charges) oppose
further
movement → ENa
= +60mV
2. EK = -90mV

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How to calculate
equilibrium potential
The membrane potential is influenced by:
• different concentration of the ions on 2 sides
of the plasma membrane
• the permeability of the plasma membrane to
each ion

Khoa Y – ĐHQG - HCM |5
How to calculate
equilibrium potential

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Resting membrane potential
1. Fewer na+
leak
channels

Changes in membrane potential

1. Depolarization: less
negative than resting
membrane potential
2. Overshoot: inside more
positive relative to outside
3. Repolarization: become
more negative but still
above resting potential
4. Hyperpolarization: more
negative than resting
potential

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Graded potential
1. Confined to a small
region & decay over
distance = decremental
2. Vary in size &
proportionate to
intensity of stimulus
3. Stimulus/inhibitory,
summate, no refractory
period


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ACTION POTENTIAL

Neurons

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Voltage-gated Na+ & K+ channels

1. Depolarization of
the membrane =
stimulus for both
channel opening
2. Repolarization of
the membrane =
the need to reset
Na+ channel
3. Refractory period
= inactivation
time of Na+
channel
Action potential
1. Rapid
2. All-or-none
3. Non decremental

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Activation & inactivation gates

Khoa Y – ĐHQG - HCM 5
Unidirectional propagation of
action potential
1. Action potential
moves one-way
along the axon
2. Absolute
refractory period
of voltage-gated
Na+ channel

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Integration of signals

Integration of signals at
initial segment

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Saltatory conduction
1. Large diameter,
myelinated axon
2. Voltage gated channels
concentrate at the node
3. Inactivation of Na+
channels ensures
unidirectional
propagation along the
axon


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METHODS OF COMMUNICATION

Modes of intercellular
communication
1. Neural communication → neurotransmitter
2. Endocrine communication → hormone
3. Neuroendocrine communication →
neurohormone
4. Local communication
– Paracrine communication → hormone
– Autocrine communication → hormone
– Gap junction

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Neural communication

• synapse
• neurotransmitter

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Chemical synapse

The synaptic vesicle cycle

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Excitatory & Inhibitory synapses
• An excitatory postsynaptic potential (EPSP) is a graded

depolarization due to influx of positive ions
• An inhibitory postsynaptic potential (IPSP) is a graded
hyperpolarization due to net influx of negative ions or net
efflux of positive ions
Neuronal network

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Lateral inhibition

Cholinergic synapses
Achetylcholin (Ach): neurotransmitter
• 2 types of receptors:
+ nicotinic: ligand gated ion channel → skeletal
muscle, brain
+ muscarinic: G-protein coupled → heart,
smooth muscle, glands, brain

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Adrenergic synapses
Catecholamine: neurotransmitter
Norepinephrine
Epinephrine
• Alpha & beta adrenergic receptors: G-protein
coupled via 2nd messenger → heart, smooth
muscle, glands

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Endocrine communication

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• Ductless
gland →
hormone.
• Hormone
→ blood
→ target
cell/tissue/
organ →
specific
receptor
13

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3. Neuroendocrine
communication

15
Local hormones:
• paracrine
communication
→ hormone
• autocrine
communication
→ hormone

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Gap junction

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8/30/2023

Giảng viên : ThS. BS. Đặng Nguyễn Tường Vân

Bài giảng lý thuyết trực tuyến Khoa Y – ĐHQG HCM |1

• Organ = functional unit

ThS. BS. Đặng Nguyễn Tường Vân

Body Fluid Compartments

Body Fluid Compartments

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân 6

ThS. BS. Đặng Nguyễn Tường Vân

Homeostatic control & reflex

ThS. BS. Đặng Nguyễn Tường Vân

Temperature reflex loops:

ThS. BS. Đặng Nguyễn Tường Vân

Temperature reflex loops:

ThS. BS. Đặng Nguyễn Tường Vân

Negative feedback loop

ThS. BS. Đặng Nguyễn Tường Vân

Positive feedback loop

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân 14

ThS. BS. Đặng Nguyễn Tường Vân 15

ThS. BS. Đặng Nguyễn Tường Vân

Giảng viên : ThS. BS. Đặng Nguyễn Tường Vân

Bài giảng lý thuyết trực tuyến Khoa Y – ĐHQG HCM |1

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

Composition of ICF and ECF

ThS. BS. Đặng Nguyễn Tường Vân

Creation of Concentration Differences

ThS. BS. Đặng Nguyễn Tường Vân

Physiologic function of the

Concentration Differences between

Characteristics of Cell Membranes

ThS. BS. Đặng Nguyễn Tường Vân

Fluid mosaic model of cell

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân 11

ThS. BS. Đặng Nguyễn Tường Vân 12

Transport across Cell

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

• Simple diffusion = not carrier

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

Giảng viên : ThS. BS. Đặng Nguyễn Tường Vân

Bài giảng lý thuyết trực tuyến Khoa Y – ĐHQG HCM |1

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân 3

Net diffusion depends on

1. Concentration gradient (C)

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

• Down an electrochemical potential gradient

ThS. BS. Đặng Nguyễn Tường Vân

Primary active transport

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

ThS. BS. Đặng Nguyễn Tường Vân

Secondary active transport