Ch 1 - Cellular Physiology Flashcards
What is interstitial fluid?
It is an ultra filtrate of plasma
Is the larger of the 2 sub-compartments in Extracellular fluid (interstitial fluid vs plasma)
What is plasma?
The fluid circulating in the blood vessels
The smaller of the 2 sub-compartments in Extracellular fluid (interstitial fluid vs plasma)
These two items make up total blood volume
Interstitial fluid & Plasma
Interstitial fluid + Plasma =
Total Blood Volume
What is Extracellular Fluid?
Contained within the integument of the animal
Fluid which bathes the cell
Major Cation of Extracellular Fluid
Na+ & Ca2+
Major Anion of Extracellular Fluid
Cl- & HCO3-
Major Cations of Intracellular Fluid
K+ & Mg2+
Major Anions of Intracellular Fluid
Proteins & organic phosphate (AMP, ADP, ATP)
ECF + ICF =
Total Body Water (TBW)
ECF = ___ of body water
1/3
ICF = ___ of body water
2/3
Percentage of Total Body Water is highest in…and lowest in…
Percentage of TBW is highest in newborns & adult males, & lowest in adult females and adults with large amount of adipose tissue (fat)
60-40-20 Rule
TBW: 60% of body weight
ICF: 40% of body weight
ECF: 20% of body weight
Extracellular Fluid is broken down into these 2 subcompartments
Interstitial Fluid & Plasma
What is osmolality?
A measure of the number of osmotically active particles per KILOGRAM of H2O
“How much sugar is in my coffee”
What is an osmole?
The number of particles into which a solute dissociates in solution
If solutes are bound to a protein are they active or inactive?
If any solutes are bounded to a protein they are inactive
What is osmolarity?
The number of osmotically active particles per LITER of total solution
Can be used interchangeably w/ osmolality (usually differ by about 1%)
What is pH?
Determined by the [concentration] of H+ ions
As H+ ions increases, pH decreases
As H+ ions decreases, pH increases
-log10[H+]
As the [concentration] of H+ ions increases
pH decreases
What is required for electroneutrality?
Each compartment must have the same concentration, in mEq/L, of positive charges (cations) as of negative charges (anions)
Anion Gap Formula
Anion Gap(plasma) = [Na+]plasma - ([Cl-]plasma + [HCO3-]plasma)
Normal Range for Anion Gap
8 - 16 meq/L
What is the anion gap?
A measurement that is useful in the diagnosis of acid-base disorders. The anion gap is based on the principle of electroneutrality: For any body fluid compartment such as plasma, the concentration of cations and anions must be equal. It accounts for the ignored anions & cations. It increases in conditions such as DM type I.
Electrolytes imbalance may result in
K+; arrhythmia
Na+; abnormal ECF osmolality, with water being shifted into or out of brain cells; seizures, coma, death
Glycerol backbone of cell membrane
Hydrophilic
Water soluble/water liking due to glycerol back bone w/ phosphate
Fatty acid tails of cell membrane
Hydrophobic
They are esterified hydroxyl groups
Water insoluble/water hating due to fatty acid tails
Tails oppose each other
Permeability of cell membrane is based on
Lipid or Water Solubility
Lipid soluble molecules & cell membrane
Uncharged
Dissolves in the hydrophobic layer & are able to cross cell membrane
»O2, CO2, steroid hormones
Water soluble molecules & cell membrane
Charged
Dissolves in the hydrophilic layer
Unable to dissolve in lipid membrane, but are able to cross water-filled channels, pores, or are transported by carriers
»Na+, Cl-, K+, Ca2+, glucose, H2O
Integral Proteins
Embedded and anchored by covalent bonds. Cannot be easily removed from cell membrane.
Transmembrane proteins have contact w/ both ECF & ICF. Some integral proteins are embedded but may not cross the membrane.
Peripheral Proteins
Not embedded in the membrane. Loosely attached by electrostatic interactions.
Located on either intra or extra cellular surface of cell.
Hydrophilic due to location
Removed by mild treatments that disrupt ionic bonds
Pores & Channels allow for
Water & Ions
Carrier proteins allow for
Facilitated diffusion; transport glucose
Pumps in cell membranes allow for
Active transport
Glycocalyx
Carbohydrates loosely attached to surface membrane
- Glycoproteins
- Glycolipids
- Proteoglycans
Tight Junctions
Zona Occludens
Attachment between cells
Occludens means to prevent/occlude
Claudins - principal structural elements of the tight junction
Adhering Junctions
Belt that encircles an entire epithelial cell just below the level of the tight junction
Functions:
»provide epithelial cells with clues about the nature and proximity of their neighbors
»initiates the assembly of a subcortical cytoskeleton as they assist in the assembly of actin, myosin, etc. – cytoplasmic cytoskeleton
Defects can lead to loss of cell organization as seen in tumors
Gap Junctions
- Low resistant pathways
- Principal structural element
• Connexin - Allows for communication between cells
• Intercellular communication - Eg:
• Current flow & electrical coupling between myocardial cells
Desmosomes
- Holds adjacent cells together tightly at a single, round spot
- Characterized by dense plaques of intermediate filaments
Simple Diffusion
- Does not require any form of energy
• Passive - Non-carrier-mediated
- Occurs down an electrochemical gradient
• Downhill - Eg: Pack of red dye in water or sugar in water
Diffusion of Electrolytes is affected by
- Potential difference across the membrane
• Electrical gradient
• Eg: K+ & Na+ - Diffusion potential
• Charged solute diffuses down a concentration gradient, based a potential difference across a membrane
Calculating Diffusion
J = -PA (C1 - C2)
J = flux (flow) P = Permeability A = Area C1 = Concentration 1 C2 = Concentration 2
What is permeability?
The ease with which a solute diffuses or passes thru a membrane
Factors affecting Permeability
- higher oil/water partition coefficient of the solute increases permeability
• Solubility of a solute in oil compared to water - lower radius of solute increases speed of diffusion
- lower membrane thickness increases diffusion by decreasing the distance travelled
Carrier-Mediated Transport has these 3 defining characteristics
- Sterospecificity -> transport is specific to isomers
- Saturation -> Transport rate increases as the concentration of solute increases until the carriers are saturated. This is when you reach Transport Maximum (Tm)
- Competition -> Structurally related solutes compete for transport sites on carrier molecule
Facilitated Diffusion
- Occurs down an electrical gradient. “Downhill”
- Does not require metabolic energy. “Passive”
- Carrier mediated & therefore exhibits sterospecificity, saturation, & competition
- At low solute concentration facilitated typically faster than simple diffusion b/c of the carrier. However @ higher concentrations the carriers become saturated & facilitated diffusion will level off
- More rapid than simple diffusion
Primary Active Transport
- Occurs against the gradient. From low -> high concentration. Uphill
- Requires a direct input of metabolic energy (ATP)
- Carrier mediated & therefore exhibits sterospecificity, saturation, & competition
- E.g.: Na+/K+ ATPase; Ca2+ ATPase; H+/K+ ATPase
Ca2+ ATPase (Ca 2+ Pump)
Transports Ca2+ against an electrical gradient in the sarcoplasmic reticulum or cell membrane
Calcium sequestration for contraction
H+/K+ ATPase (H+/K+ Pump)
Locations:
• Parietal cells of gastric mucosa
• alpha-intercalated cells of renal collecting duct
Secondary Active Transport
Transport of two or more solutes is coupled
Requires an INDIRECT input of metabolic energy
Metabolic energy is provided indirectly by the Na+/K+ pump
Co-transport or symport: If the solutes move in the same direction across the cell membrane
Counter-transport, exchange, or anti-port: If solutes move in opposite direction
Can you answer these for simple diffusion?
1.) Active or Passive? 2.) Carrier-Mediated? 3.) Uses Metabolic Energy? 4.) Dependent on Na+ gradient?
- ) Passive; downhill
- ) Not Carrier-Mediated
- ) No energy
- ) Not dependent on Na+ gradient
Can you answer these for facilitated diffusion?
- ) Active or passive?
- ) Carrier-Mediated?
- ) Uses Metabolic Energy?
- ) Dependent on Na+ Gradient?
- Passive; downhill
- Yes; Carrier-Mediated
- No Metabolic Energy used
- Not dependent on Na+ gradient
Can you answer these for Primary active transport?
- Active or Passive?
- Carrier-Mediated?
- Uses Metabolic Energy?
- Dependent on Na+ Gradient?
- Active; uphill
- Yes; Carrier-Mediated
- Yes: direct input of metabolic energy
- Not dependent on Na+ gradient
Can you answer these on Cotransport?
- Active or Passive?
- Carrier-Mediated?
- Uses Metabolic Energy?
- Dependent on Na+ Gradient?
- Secondary Active
- Yes; Carrier-Mediated
- Yes; Indirect Metabolic Energy
- Yes (Solutes move in same direction as Na+ across cell membrane)
Can you answer these on Countertransport?
- Active or Passive?
- Carrier-Mediated?
- Uses Metabolic Energy?
- Dependent on Na+ Gradient?
- Secondary Active
- Yes; Carrier-Mediated
- Yes; Indirect input of Energy
- Yes (solutes move in opposite direction as Na+ across cell membrane)
What is Osmosis?
- Flow of water across a semi-permeable membrane from low to high concentration
- Membrane is impermeable to solute. Osmotic pressure, gradient is created
- Osmosis is due to [conc.] & pressure difference
- Diffusion is due to [conc.] difference
Osmolarity Formula
g x C = Osmolarity
-Osmolarity = conc. of particles (osm/L)
-G = # of particles in a solution (osm/mol)
-C = conc. (mol/L)
What is the osmolarity of 1 M NaCl? Osmolarity = g x C = 2 osm x 1 M = 2 osm/L
Differences in Osmolarity
Isosmotic = equal osmolarity Hyperosmotic = higher osmolarity Hyposomotic = lower osmolarity
Osmotic Pressure
- The difference in [conc.] created by the two solutions across a semipermeable membrane
- Provides the energy or force for water to flow thru the membrane
- The greater the difference in osmolarity between two solutions, the greater the pressure
Van’t Hoff’s Law
π = RT x gC
π = Osmotic pressure (mm Hg or atm) G = # of particles in solution (osm/mol) R = gas constant (0.082 L-atm/mol-K) T = absolute temperature (K) C = conc. (mol/l)
If a cell is put in a Hypotonic solution…
Water moves into the cell
If a cell is put in a Hypertonic solution…
Water leaves the cell
Reflection Coefficient
Value between 0 to 1 which indicates the ease with which a solute permeates or crosses a membrane.
A reflection coefficient of 1 indicates the solute is impermeable and is retained with compartment. Osmotic pressure is created; osmosis occur.
A reflection coefficient of 0 indicates the solute is completely permeable. No osmotic pressure; no osmosis
What is the effective osmotic pressure?
It is the product of osmotic pressure and the variable of reflection coefficient
Voltage-gated channels
Regulated by changes in membrane potential
Ligand-gated channels
Regulated by hormones, 2nd messengers, or neurotransmitters
Diffusion Potential
- Created by the movement of only a few ions
- Does not cause changes in the [conc.] of solution bulk
- Generated only if the membrane is permeable to the ion
- Size of potential depends on size of concentration difference
- Measured in millivolts (mV)
Equilibrium Potential
It’s the diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a concentration difference
Same on both sides
Net diffusion is zero
Electrochemical Potential
The concentration and ion gradient generated by a solution
The Nernst Equation
Tells at what potential an ion would be at electrochemical equilibrium
Resting Membrane Potential
Definition: Voltage of the cell at rest.
Due to high resting conductance to K+ at rest when Na+ channels are closed
Maintained by Na+/K+ pump
Action Potentials
A transient change in the resting membrane. The mechanism of excitation of cells
Depolarization
-Making the membrane potential less negative or more positive due to influx of Na+; inward current
Hyperpolarization
Making the membrane potential more negative due to outflux of K+; outward current
The outflux of K+ is responsible for hyperpolarization
Threshold potential
Point of no return
Inevitability of action potential
Overshoot
Portion of the Action Potential where the membrane potential is positive (cell interior positive)
Above 0 mV
Undershoot
Portion of the Action Potential, following repolarization, where the membrane potential is actually more negative than it is at rest
Refractory Period
Period during which another normal action potential may not be elicited in an excitable cell
Absolute Refractory Period
Another Action Potential cannot be elicited regardless of the size of the stimulus due to utilization of all Na+ channels
Relative Refractory Period
Another Action Potential can be elicited if the stimulus is larger than normal. Na+ are beginning to recover
2 Types of Synapses
- Electrical - current flow from one excitable cell to the next via low resistance pathways; gap junctions. E.g: cardiac/smooth muscle. Are fast
- Chemical - neurotransmitters are transmitted via synaptic cleft. Action potential causes the release of NT (-ve/+ve) from presynaptic terminal into synaptic cleft via influx of Ca2+. Slow
Botulin Toxin
Action: Blocks ACh release from presynaptic terminal
Effect on Neuromuscular Transmission: Total blockade, paralysis of respiratory muscles, & death
Curare
Action: Competes w/ ACh for receptors on motor end plate
Effect on Neuromuscular Transmission: Decreases size of EPP; in maximal doses produces paralysis of respiratory muscles & death
Neostigmine
Action: AChE inhibitor (anticholinesterase)
Effect on Neuromuscular Transmission: Prolongs and enhances action of ACh at motor end plate
Hemicholinium
Action: Blocks reuptake of choline into presynaptic terminal
Effect on Neuromuscular Transmission: Depletes ACh stores from presynaptic terminal
Excitatory Postsynaptic Potentials (EPSP)
Excitation or depolarization of postsynaptic membrane
Produced by opening Na+ and K+ channels
Neurotransmitters: ACh, epi, norepi, glutamate, & serotonin
Inhibitory Postsynaptic Potentials (IPSP)
Inhibition or hyperpolarization of postsynaptic membrane
Opening Cl- channels
Membrane potential driven towards the Cl- equilibrium potential (approximately -90 mV), which is a hyperpolarized state
Neurotransmitters: y-aminobutyric acid (GABA A receptor) and glycine (GlyR)
Spatial Summation
Simultaneous arrival of Action Potential
Excitatory = greater depolarization than if single
Excitatory + inhibitory = will cancel each other out
Acetylcholine
Only neurotransmitter that is utilized at the neuromuscular junction
Neurotransmitter of preganglionic neurons
Norepinephrine
Synthesized in adrenal medulla from dopamine
Primary NT released from postganglionic sympathetic neurons
Epinephrine
Synthesized in adrenal medulla
Dopamine
Prominent in midbrain neurons
Inhibits prolactin
Neurons reduced in Parkinson’s dz
Serotonin
Produced from tryptophan in serotonergic neurons in the brain and in the gastrointestinal tract
Present in high concentration in brain stem
Converted to melatonin in pineal gland
Glutamate
Most prevalent excitatory NT in brain
Receptor Types: 3 are ionotropic receptors, or ligand-gated ion channels, including the NMDA (N-methyl-D-aspartate) receptor
Metabotropic Receptors; GTP
Histamine
Synthesized from histidine
Release by mast cells
Glycine
Found primarily in spinal cord & brain stem
Inhibitory
y-Aminobutyric Acid (GABA)
Most common inhibitory NT of brain
Barbituates
Benzodiazapines (modulates GABA)
Nitric Oxide (NO)
Inhibitory
Vasodilator
Neurohormones
Does the job
E.g: GABA, Glutamate, ACh
Neuromodulators
Think they can do the job. “Wanna be’s”
Eg: endorphins, substance P, serotonin
Prominent in midbrain neurons
Inhibits prolactin
Neurons reduced in Parkinson’s dz
Dopamine
Present in high concentration in brain stem
Converted to melatonin in pineal gland
Serotonin
Types of Adhesion Molecules
Cell-Matrix Adhesion Molecules; connect cell to outer cellular matrix
Cell-cell Adhesion Molecules; cells to other cells
Loss of cell adhesion molecules is observed in
Metastatic Tumors
Functions of Glycocalyx
Functions:
- Due to their -ve charge, they repel -ve charged substances
- attachment to other cells
- receptors
- immune reactions
Principal structural elements of the tight junction
Claudins
Function of Adhering Junctions
Provide epithelial cells with clues about the nature and proximity of their neighbors
Initiates the assembly of a subcortical cytoskeleton as they assist in the assembly of actin, myosin, etc
Cytoplasmic cytoskeleton
Principal structural unit of gap junctions
Connexin
Dopamine is the precursor to
Norepinephrine
Norepinephrine is the precursor to
Epinephrine
