Cell Physiology

Front 1

What are the 2 major fluid compartments of the body?

Back 1

1) ECF, consists of 1/3 of total body water
2) ICF, consists of 2/3 of total body water

Front 2

What are the 2 subcompartments of ECF?

Back 2

1) plasma
2) interstitial fluid (ultrafiltrate of plasma)

Front 3

1) What is the most significant difference in composition b/n plasma and interstitial fluid?

2) Explain the Gibbs Donnan Equilibrium.

Back 3

1) presence of proteins (albumin)

2) Plasma compartment (PC) contains impermeable, negatively charged proteins. To maintain electroneutrality, PC must have slightly lower concen of small anions and slightly higher concen of small cations than that of IF

Front 4

What are 3 units used to measure solute concentrations?

Back 4

moles, equivalents, osmoles

Front 5

Define the principle of electroneutrality.

Back 5

Each compartment must have the same concentration of positive charges (cations) and negative chargesh (anions)

Front 6

What is the solute composition (anions, cations) of ECF and ICF?

Explain the relationship of Ca and pH in the ICF and ECF?

Back 6

ECF: Na, HCO3, Cl
ICF: K, Mg, organic phosphates, proteins
ECF ICF
Na (mEq/L) 140 14
K (mEq/L) 4 120
Cl (mEq/L) 105 10
HCO3 (mEq/L) 24 10
Ca (mEq/L) 2.5 10^-4
pH 7.4 7.1
osmolarity 290 290

Front 7

Describe the model and composition of cell membrane.

Back 7

Fluid mosaic model: distribution of proteins in a phospholipid bilayer

lipid component: phospholipids, glycolipids, cholesterol
responsible for high permeability for lipid soluble substances: O2, CO2, fatty acids, steroid hormones
and low permeability for water soluble substances

protein component:
integral: anchored to lipid bilayer by hydrophobic bonds
peripheral: anchored to lipid bilayer by electrostatic interactions

Front 8

List 2 examples of peripheral proteins.

Back 8

1) Hormone receptors
2) Cell surface antigens

Front 9

List 4 examples of integral proteins.

Back 9

1) transporters
2) enzymes
3) ion channels
4) water channels

Front 10

What are the 2 types of membrane transport and what differentiates them?

Back 10

1) downhill transport
2) uphill transport

requirement or lack thereof of input of metabolic energy

Front 11

List 2 ways downhill transport occurs.

Back 11

1) simple diffusion
2) facilitated diffusion

Front 12

List 2 ways uphill transport occurs.

Back 12

1) primary active transport
2) secondary active transport

direct vs indirect input of metabolic energy

Front 13

List 2 types of secondary active transport.

Back 13

1) cotransport (symport)
2) countertransport (antiport, exchanger)

Front 14

List 3 features of carrier mediated transport and describe each.

Back 14

1) saturation: limited number of binding sites for solute, reached at transport max, Tm
2) stereospecificity
3) competition

Front 15

Define flux/flow (J) for simple diffusion.

Back 15

Flux is the net diffusion of solute across a permeable membrane, it depends on:
1) size of concentration gradient (driving force)
2) partition coeff, K
3) diffusion coeff, D
4) thickness of membrane, Δx
5) surface area available for diffusion, A

Front 16

Define the partition coefficient, K.

Back 16

1) K describes the solubility of solute in oil relative to its solubility in water
2) The greater the relative solubility in oil, greater the coeff and more easily it can pass through membrane.
3) Nonpolar solutes have greater K than polar solutes

Front 17

Define diffusion coeff, D.

Back 17

D depends on size of solute and viscosity of medium.

Front 18

What is the equation for flux?

Back 18

J=PA(Ca-Cb)

P=permeability and encompasses K, D, Δx for simplicity of equation
P=KD/Δx

Front 19

What 2 additional consequences should we be aware of when the diffusing solute is an electrolyte or ion instead of a nonelectrolyte (dissolves in solution without ionizing)?

Back 19

1) net rate of diffusion altered: if there is a potential difference across a membrane, it will alter the net rate of diffusion of a charged solute
2) generation of diffusion potential: when a charged solute diffuses down a concentration gradient, that diffusion can itself generate a potential difference across a membrane

Front 20

Compare and contrast simple and facilitated diffusion.

Back 20

Compare: both occur down an electrochemical gradient, require no energy input

Contrast:
1) Facilitated diffusion (FD) uses a membrane carrier so exhibits all features of carrier mediated transport
2) at low solute concen, FD occurs faster bc of fx of carrier
3) at high solute concen, FD levels off bc carrier becomes saturated, SD will continue as long as there is a concen gradient

Front 21

Give an example of a transporter that demonstrates stereospecificity.

Back 21

Glucose transporter on renal proximal tubule is specific for natural isomer D-glucose, not L-glucose

Front 22

Give an example of a transporter that demonstrates competition.

Back 22

Glucose transporter may bind D-galactose instead of D-glucose.

Front 23

Give an excellent example of FD.

Back 23

GLUT4 transporter=transports D-glucose into skeletal muscle and liver cells, this transport can proceed as long as blood glucose concen is higher than intracelluar concentration and GLUT4 transporters are not saturated.
Note: L-glucose is a nonphysiologic stereoisomer that is not recognized by our GLUT4 carriers so not bound or transported.

Front 24

Name 3 examples of primary active transport in physiological systems and where are they located?

Back 24

1) Na-K ATPase (all cell membranes)
2) Ca ATPase (SR, mitochondrial membrane, cell membrane)
3) H-K ATPase (parietal cells of gastric mucosa, α intercalated cells of renal collecting duct)

Front 25

Explain the structure, function, stoichiometry of the Na-K pump. What does electrogenic mean?

Back 25

Na-K pump (E) consists of α and β subunits, α subunit contains ATPase activity and binding sites of Na and K. E binds ATP, hydrolyzes it, and the terminal phosphate is transferred to the enzyme producing high energy E-P. E-P binds ICF Na, undergoes conformational change, rotates to ECF side where it releases Na and binds K. When K is bound, P is released converting E to original form which rotates back to IC side and releases K. Ready to begin new cycle. It pumps out 3 Na and pumps in 2 K.
Electrogenic process means more positive charge is pumped out of cell than is pumped into the cell which creates charge separation and potential difference

Front 26

What are cardiac glycosides and explain how they work? Give 2 examples.

Back 26

Drugs that inhibit Na-K pump by binding to E-P form in ECF disrupting the cycle of phosphorylation-dephosphorylation and therefore the entire enzyme cycle. Ex: ouabain and digitalis
Inhibition of the Na-K pumps diminishes the Na concen gradient and therefore all secondary AT processes are diminished

Front 27

What is the function and stoichiometry of the Ca ATPase?

Back 27

It is responsible for maintaining a very low level of intracellular Ca. 1-2 Ca ions are transported for each ATP hydrolyzed.

Front 28

What is the function of the H-K pump? Name a drug that inhibits this pump.

Back 28

It pumps H from ICF of parietal cells to lumen of stomach, where it acidifies gastric contents.

Omeprazole is an inhibitor of gastric H-K ATPase, reduces secretion of acid and can treat some types of ulcer diseases.

Front 29

Name the important cotransporters in the body?

Back 29

1) Na-amino acid cotransport
2) Na-glucose cotransport (SGLT1 in intestinal epithelial cells on lumenal side), both solutes are required for this protein to rotate
3) Na-K-2Cl cotransport (luminal membrane of epithelial cells of ascending limb)

1 and 2) present in lumen of epithelial cells of small intestine and renal proximal tubule

Front 30

Name the important countertransporters in the body?

Back 30

1) Na-Ca exchanger (3 Na enter cell and 1 Ca leaves cell), electrogenic (3 positives enter, 2 positives leave)
2) Na-H

Front 31

Clinical Correlate:

Explain the relation bn Diabetes Mellitus Type 1 and Na-Glucose cotransporter in renal proximal tubules.

Back 31

In DM1, pancreatic β cells cannot produce insulin so glucose cannot be uptaken. Glucose is normally filtered at the glomerular capillaries and reabsorped by the Na-glucose cotransporter on the epithelial cells of the renal proximal tubule. This carrier has a Tm that when reached, cannot transport more glucose. The remaining filtered glucose cannot be absorbed and therefore is excreted in the urine.

symptoms: frequent urination and excessive thirst, glucosuria
clinical tests: glucose tolerance test, urine dipstick

Front 32

Define osmosis.

Back 32

The flow of water across a semipermeable membrane due to differences in solute concentration, the concentration differences of impermeable solutes establish osmotic pressure differences and this osmotic pressure difference causes water to flow by osmosis.
Osmosis is NOT diffusion of water
osmotic pressure=driving force

Front 33

Define osmolarity.

Back 33

The concentration of osmotically active particles.
To calculate, we need to know concentration of solution (C) and whether solute dissociates completely or partially (g)

Osmolarity=gC
1<g<2, where 1 means no dissocation

terms: isosmotic, hyperosmotic, hypoosmotic

Front 34

Explain concept of osmosis.

Back 34

Say we have a container of distilled water that is open to the atmosphere with a semipermeable membrane. there is no osmotic pressure or hydrostatic pressure on either side. say we add solute (NaCl) to side A. now, side A has an osmotic pressure and there is a decrease in the hydrostatic pressure due to the interaction of the solute molecules with the pores of the semipermeable membrane. now if we seal the container and apply a piston to solution 1 to stop the flow of water, this is the effective osmotic P

Front 35

What is the equation to calculate osmotic p?
Explain the factors?

Back 35

van't Hoff equation:
pi=gC(sigma)RT

Sigma=reflection coefficient, describes the ease with which a solute crosses a membrane
1=impermeable solute, so it will be retained in solution and exert its full osmotic p, ex: serum albumin and intracellular proteins
0=freely permeable solute, there is no effective osmotic pressure, ex: urea
when sigma is a value bn 0 and 1= the effective osmotic p lies bn the maximal value and 0

Front 36

What does the reflective coeff measure?

Explain the concept of tonicity bn 2 solutions with varying reflective coefficients.

Back 36

ref coeff measures the ease with which a solute crosses a membrane

2 solutions are isotonic if there is no effective osmotic pressure difference bn them, no water will flow

when 2 solutions have different osmotic pressures, the one with the higher press is hypertonic and one with lower is hypotonic, water will flow from hypotonic solution to hypertonic sol (remember that solution with greater osmotic p has lower hydrostactic pressure due to interaction of solute particle with pores of semipermeable membrane so water flows from solution with lower solute concen to solution with higher concen)

Front 37

What is the difference bn osmosis vs diffusion?

Back 37

Osmosis of water is faster than the diffusion of water.

The driving force for osmosis is pressure difference. The flow of water is proportional to the radius of the pores in the semipermeable membrane raised to the 4th power.

The driving force for diffusion is concentration difference.
The flow of water is proportional to the surface area of membrane, thus radius raised to 2nd power

Front 38

List the 8 terms used to describe an action potential in the order it occurs.

Back 38

depolarization
inward current
threshold potential
overshoot
repolarization
outward current
undershoot
refractory period

Front 39

List the 3 basic characteristics of action potentials.

Back 39

size and shape
propagation
all-or-none response

Front 40

What is propagation dependent on?

Back 40

conduction velocity=speed at which an AP travels along a nerve axon or muscle fiber

dependent on cable properties

Front 41

What are cable properties?

Back 41

the name of the concepts that explain how nerves and muscles act as cables to conduct electrical activity

Front 42

What are the 2 cable properties that conduction velocity is dependent on?

Back 42

1) time constant=indicates how quickly an axon depolarizes due to an inward current and how quickly it will hyperpolarize due to an outward current

2) length constant=indicates how far a depolarizing current will spread along the axon

T=RC

Front 43

What affects the time constant?

Back 43

1) membrane capacitance=ability of membrane to store charge
2) membrane resistance=how quickly the charge can flow along the membrane

Front 44

What affects length constant?

Back 44

1) membrane resistance
2) internal resistance

lambda=square root (Rm/Ri)

Front 45

What 2 mechanisms increase conduction velocity?

Back 45

1) increasing nerve diameter (lowers Ri)
2) myelination (increases Rm)

Front 46

What is a synapse?

Back 46

site where information is transmitted from one cell to another

Front 47

What are 2 types of synapses?

Back 47

1) electrical
2) chemical

Front 48

Describe electrical synapse: function, advantage, location.

Back 48

Allows transmission of info via low resistance pathways called gap junctions

Advantage: FAST cell to cell conduction, bidirectional

Location: smooth muscle like uterus (labor contractions), bladder (quick urination), GI tract (peristalsis) and in cardiac ventricular muscle (quick heart beat)

Front 49

Describe chemical synapse and the steps involved in a chemical neurotransmission (in brain or neuromuscular junction)

Back 49

Has a synaptic cleft and is unidirectional. Allows for signals from multiple neurons to feed into one neuron or one neuron to feed multiple synapses (or multiple motor end plates)

Steps: AP reaches presyn terminal, Ca channels open, influx of Ca, vesicles carrying NTs fuse with membrane, NTs are released into synaptic cleft, NTs bind to receptors on postsyn memb

Front 50

Nature of NTs

Back 50

1) excitatory-cause depolarization
2) inhibitory-cause repolarization

Front 51

List 4 agents affecting neuromuscular transmission.

Back 51

1) botulinum toxin=prevents exocytosis of Ach (muscle paralysis)
2) curare=competes with Ach on nicotinic receptor (muscle paralysis); ex: D-tubocurarine, α-bungarotoxin
3) neostigmine=inhibits AchE
4) hemicholinium=blocks reuptake of choline, prevent formation of Ach

Front 52

Describe myasthenia gravis and list 2 therapeutic drugs.

Back 52

Autoimmunie disease characterized by muscle paralysis and fatiguability due to block of Ach receptors by body's antibodies

Drugs: neostigmine, pyridostigmine

Front 53

What are the 3 types of synaptic arrangements?

Back 53

1) one to one (ex. motoneuron to muscle fiber)
2) one to many (amplification of activity)
3) many to one (summation of inputs necessary to generate AP on postsyn cell)

Front 54

excitation contraction coupling

Back 54

mechanism that translates APs into contractions,

Ca plays CENTRAL role and skeletal and smooth muscle contractions

Front 55

How does the AP cause skeletal muscle contraction?

Back 55

depolarization of presynaptic terminal-->opening of Ca channels-->Ca binds to troponin (I, T, C)-->cause conf change in tropomyosin-->unblock myosin binding sites from actin filaments; myosin thick filament binds to ATP-->hydrolysis causes myosin to bind to actin thin filaments and power stroke pulls thin filaments together leading to contraction

Front 56

How does the AP cause smooth muscle contraction?

Back 56

depolarization of smooth muscle cell opens Ca channels-->IC Ca binds to calmodulin-->Ca-calmodulin complex phosphorylates MLCK-->phosphorylates MLC-->binds to actin to form cross bridges; the tension generated is proportional to the number of cross bridges which is prop to the amount of IC Ca

Front 57

facilitation
augmentation
posttetanic potentiation

Back 57

phenomena that cause a greater response by the postsynaptic cell due to repeated stimulation

Front 58

synaptic fatigue

Back 58

repeated stimulation produces a smaller than expected response in postsynaptic cell

Front 59

list the 4 categories of neurotransmitter substances

Back 59

1) Ach
2) biogenic amines
3) amino acids
4) neuropeptides

Front 60

Explain the vital importance of Ach.

Back 60

1) only NT at neuromuscular junction
2) PNS: NT released from ALL preganglionic and postganglionic neurons
3) SNS: NT released from preganglionic neurons
4) NT release from presynaptic neurons of adrenal medulla

Front 61

List 5 important biogenic amines NTs.

Back 61

Epi
NE
dopamine
serotonin
histamine

Front 62

The biogenic amines have the same precursor and biosynthetic pathway. Provide the precursor, pathway with involved enzymes.

Back 62

Precursor=tyrosine converted to L dopa by tyrosine hydroxylase--> L-dopa is converted to dopamine (dopaminergic neurons) by dopa decarboxylase--> (adrenergic neurons) dopamine is coverted to NE by dopamine b-hydroxylase-->(adrenal glands) NE is converted to Epi via PMNT

Front 63

List the 2 degradative enzymes of biogenic amines and describe them.

Back 63

COMT (made in liver) and MAO (found in presynaptic terminal); one or the other or both can degrade the amines. for degradation to occur, the amines must be reuptaken to presynaptic terminal. these enzymes can degrade the amines at dopaminergic neurons, adrenergic neurons, and adrenal glands.

Front 64

Where are degraded amines found and what is the major metabolite of NE and Epi?

Back 64

In urine

NE-->normetanephrine
Epi-->metanephrine
NE + Epi-->VMA

Front 65

What is the precursor of serotonin and what neurons release it? What other product is serotonin a precursor to and where does this conversion take place?

Back 65

precursor=tryptophan, serotenergic neurons in the brain and GI tract

serotonin-->melatonin in pineal gland

Front 66

What is the precursor of histamine and where is it released from?

Back 66

precursor=histidine, released from neurons in hypothalamus and mast cells of GI tract

Front 67

List 3 important amino acid NTs.

Back 67

glutamate (excitatory)
GABA (inhibitory)
glycine (inhibitory, increase Cl conductance)

Front 68

What is the most prevalent excitatory NT in the brain?
What parts of nervous system does it play a significant role?

Back 68

glutamate

spinal cord and cerebellum

Front 69

List 11 important neuropeptide NTs.

Back 69

ACTH
oxytocin
vasopressin
cholecystokinin
dynorphin
endorphins
enkephalins
neurotensin
substance P
TRH
VIP

Front 70

What is the precursor to GABA and what neurons is it released from? What metabolic function does GABA play?

Back 70

glutamate, GABAergic neurons

GABA plays no metabolic function like glutamate and glycine (incorporated into proteins)

Front 71

What are the 2 GABA receptors and explain their importance?

Back 71

GABAa receptor=when GABA binds to it, it increases Cl conductance (inhibitory); site of action of benzodiazapenes and barbituates

GABAb receptor=when GABA binds to it, it increases K conductance (inhibitory)

Front 72

What disease is associated with GABA deficiency?

Back 72

Huntington's disease: characterized by hyperkinetic choreiform movements; uncontrolled movements are attributed to lack of GABA dep inhibition neural pathways

Front 73

List 3 functions of neuropeptides.

Back 73

1) neuromodulator
2) neurohormones
3) neurotransmittors

Front 74

What is a neuromodulator?

Back 74

1) controls the amount of NT released from presynaptic membrane
2) controls the response of NT on postsyn membrane

Front 75

What is a neurohormone?

Back 75

released from neurons into blood to act at distant sites

Front 76

How are neuropeptides different from the classical NTs (Ach, biogeneic amines) ?

Back 76

1) copackaged and cosecreted from presynaptic terminals along with classical NTs
2) synthesized in nerve cell bodies instead of presynaptic terminal (once the polypeptides are transported to secretory vesicles, these vesicles are transported down the axon to presynaptic terminal where they become synaptic vesicles)