Cellular Anatomy &
Physiology
Charles C. Cook, MD
Membrane transport
If only it was that easy!
Osmosis
• The flow of water across a semipermeable
membrane from a solution of low solute to
a solution of high solute
Body Fluids & Their Compartments
• Total body water—TBW
– 60% of body weight
• Distribution of TBW
– Intracellular fluid (ICF)
• Two-thirds of TBW
• Major cations are K+ and Mg2+
• Major anions are protein and organic phosphates
(ADP, ATP, AND AMP)
Distribution of water (cont.)
– Extracellular fluid (ECF)
• One-third of TBW
• Composed of interstitial fluid and plasma
• Major cation is Na+
• Major anions are Cl- and HCO3– Plasma is one-fourth ECF
 Plasma proteins are albumin and globulins
– Interstitial fluid is three-fourths of ECF
 Is an ultrafiltrate of plasma (has very little protein)
Distribution of water (cont.)
• 60-40-20 rule
– TBW is 60% of body weight
– ICF is 40% of body weight
– ECF is 20% of body weight
Compartments
• To measure accurately one needs:
– A substance that will stay in only one
compartment
– Substance is non-toxic
– Substance has no direct effect on distribution
of water
– Substance mixes fairly quickly and evenly in
the compartment
– Substance is easily measured
Measuring the Different Fluid
Compartments
• Dilution method
– Place a known amount of substance that stays in one
compartment
– Examples
• Tritiated water and D O for TBW
• Mannitol, inulin, and sulfate for ECF
• Evans blue and radioiodenated tagged serum albumin for
2
plasma
• Interstitial =ECF vol-plasma vol
• ICF= TBW-ECF vol
Clinical Correlation
• In infants and children their ECF/ICF ratio
is larger but their absolute ECF is less than
adults and this is why they tend to
dehydrate faster and more severely than
adults exposed to the same stressors.
Movement Across the Cell
Membrane
• Simple diffusion
• Carrier-mediated transport
• Facilitated diffusion
• Primary active transport
• Secondary active transport
Simple Diffusion
• Not carrier mediated
• Flows down an electrical gradient
• Does not require energy
Facilitated diffusion
• Characteristics:
– Moves “downhill” on an electrochemical
gradient (similar to simple diffusion)
– Does not require energy
– Faster than simple diffusion
– Carrier mediated*
Facilitated diffusion (cont)
• Examples:
– Transport of glucose in muscle and fat cells
• “downhill”
• carrier-mediated
• competitive (galactose)
Carrier-mediated transport
• Includes facilitated diffusion, primary and
•
secondary active transport
Characteristics:
– Stereospecificity—D-glucose and L-glucose
– Saturation—transport increases until all carriers are
saturated then become steady-state
– Competition—structurally related solutes compete i.e.
galactose and glucose in small bowel
Clinical Correlation
• In patients with diabetes mellitus, glucose
uptake by the muscle and adipose cells is
impaired because the carriers for
facilitated diffusion of glucose require
insulin. Knowing that serum glucose is
elevated, applying what we know about
solute movement, what can we see
occurring in a patient?
Primary active transport
• Characteristics:
– Occurs against an electrochemical gradient
(“uphill”)
– Requires energy in the form of ATP (hence
the ‘active’)
– Is carrier mediated*
Primary active transport (cont)
• Examples:
– Na-K pump: located in the cell membrane and
transports Na from intracellular to
extracellular fluid and K in the opposite
direction. Na and K are moved against their
electrochemical gradient. ATP is used as
energy source and the usual exchange is
3 Na/2 K. This is where the cardiac glycoside
drugs oubain and digitalis work.
Primary active transport (cont)
• Examples (cont):
– Ca pump: In the sarcoplasmic reticulum or
cell membrane Ca is moved against an
electrochemical gradient
– Proton pump: Parietal cells in the stomach
pump H+ into the lumen against a gradient.
Omeprazole blocks this action.
Secondary active transport
• Characteristics:
– Transport is coupled with two or more
solutes.
– One solute is transported “downhill” and
provides the energy needed for the “uphill”
transport.
– Metabolic energy is provided indirectly from
the Na gradient that is maintained across
the cell membrane.
Secondary active transport (cont)
• Characteristics (cont)
– If solutes move in same direction it is called
cotransport or symport.
– If solutes moved if opposite directions it is
referred to as countertransport, exchange
or antiport.
Secondary active transport (cont)
• Examples:
– Na-glucose cotransport in the luminal
membrane of intestinal mucosal and proximal
tubule cells.
– Na-Ca countertransport or exchange.
Transports Ca “uphill” from low IC to high EC
and Na moves in opposite direction
“downhill”.**
Membrane Potential
• Definition
– A membrane potential is the voltage across a
cells’ membrane. This occurs because of the
movements of charged particles across the
membrane. (See, I told you that all that
transport stuff really would be useful!)
Resting Membrane Potential
• This is simply the voltage across the
membrane at rest.
• This voltage is measured in millivolts (mV)
• Ranges from -20 to -200 mV
• These cells are polarized.
• The cell membrane is more permeable to
K than Na and the pump does not work in
a 1:1 ratio.
Resting Membrane Potential (cont)
• This keeps the inside of the cell
membrane negatively charged in relation
to the outside.
• Therefore K ions have the most influence
on the resting membrane potential.
Cell Organelles
1.
2.
3.
4.
5.
6.
7.
Cell wall (plasma membrane)
Mitochondria
Lysosomes
Peroxisomes
Cytoskeleton
Centromeres
Cilia

Cell Organelles (cont)
8. Cell adhesion molecules
9. Intercellular connections
10.Gap junctions
11.Endoplasmic reticulum
12.Ribosomes
13.Golgi apparatus
14.Nucleus
The Cell Membrane
Made up of:
1. Lipids
2. Proteins
– Referred to as the plasma membrane
– Double layer of lipids or bilayer with proteins
–
interspersed
Lipid layer is primarily phospholipids but
smaller amounts of cholesterol and glycolipids
are present.
Plasma membrane
• The heads of lipid bilayer are hydrophilic and
•
•
polarized.
The tails (fatty acid chains) are hydrophobic and
nonpolar. These are oriented toward the middle
of the membrane.
Proteins may extend all the way through the
wall (integral proteins) while others are either
inside or outside the membrane.
Plasma membrane
• Functions of the protein:
– Cell adhesion
– Pumps
– Carriers
– Ion channels
– Receptors
– Enzymes
Functions of the plasma membrane
Mitochondria
• The powerhouse of the cell
• Forms ATP through oxidative
phosphorylation
• The more active a tissue the more
mitochondria
• Has its own genome (always from the
mother)
• Mitochondrial DNA diseases
Lysosomes
• Function:
– Consumes and digests worn-out cell
components and external material such as
bacteria that have been endocytosed.
– Contain enzymes
• More acidic than rest of the cytoplasm
( ph 5.0)
• Arise from the Golgi apparatus
Lysosomes
• Lysosomal storage diseases
– Fabry’s disease
• Multi-organ function, pain
– Gaucher’s disease
• FTT, hepatosplenomegaly
– Tay-Sachs disease
• Ashkenazi Jews, MR, blindness
Peroxisomes
• Membranous sacs that contain powerful
•
•
•
enzymes esp. oxidases and catalases.
Oxidases use molecular oxygen to detoxify
harmful substances (ETOH & formaldehyde)
Most important function of oxidases is to
neutralize free radicals
Peroxisomes are numerous in the liver and
kidneys.
Cytoskeleton
• Fibers that give the cell its shape and
ability to move.
• Main fibers:
– Microtubules
– Microfilaments
– Intermediate filaments
Cytoskeleton (cont)
• Microtubules
– Largest of the three rods
– Radiate out from the centrosome
– Determine the overall shape of the cell
– Mitochondria, lysosomes, and secretory
granules attach to these and are moved by
motor proteins
Clinical Correlation of Microtubules
• Microtubule assembly is prevented by
colchicine and vinblastine. Taxol binds
with them so that organelles cannot move.
Due to the functions of these drugs,
mitotic spindles can’t form and cells die.
In this case cell death is good because it
stops the formation of uric acid crystals
and cancer cells (breast)
Cytoskeleton (cont)
• Intermediate filaments
– Help the cell resist external pressure
– Their absence causes cells to rupture easily
Cytoskeleton (cont)
• Microfilaments
– Long strands of protein called actin which is
the most abundant protein in mammals
– Are associated with motion of some type
• Myosin
• Cell division
• Amoeboid motion
• Endocytosis
• Exocytosis
Centrosomes
• Centrosomes act as a microtubule
organizing center
• Within the centrosome are 2 centrioles
which form the basis of cilia and flagella
Cilia