Constanzo Chapter 1 - Cellular Physiology

What composes your total body water?

ICF (2/3) and ECF (1/3) separated by the cell membrane.

What are the two main components of ECF?

Interstitial fluid and plasma separated by the capillary wall.

What is a mole?

The amount of solute

What is the common unit for biological molarity?

mmol/L

What is an equivalent?

The number of moles times the valence.

What happens in a positive feedback loop?

When the presence of the end product stimulates the pathway to continue, i.e oxytocin and contractions.

What are some basic homeostatic conditions?

External environment excites reactions in the body which causes an internal disturbance. Homeostasis is the body's ability to keep the internal environment in a narrow range.

What happens in a negative feedback loop?

When a change in the amount of the end product reduces/combats the original stimuli. I.e Insulin

What are common things regulated by homeostasis?

Water, H+, Ca++, O2, temperature, electrolytes, and energy supplying material (ATP).

What is the principle of macroscopic electroneutrality?

Each body compartments must have same concentration of cations and anions.

What are the balancing ions for Na+? What are the balancing ions for K+?

ECF Na+= Cl- and HCO3-

ICF K+= Protein and organophosphates

Describe the Ca+ levels in the ICF and ECF?

High Ca+ in the ECF, and low Ca+ in the ICF.

How are the osmolarities of the ICF and ECF the same?

Water distribution due to osmosis.

Which molecules have a higher concentration outside the cell?

Na= 140,40

Ca=0.0001

Cl= 105,10

HCO3-= 24,10

pH= 7.4 (basic)

Which molecules have a higher concentration inside the cell?

K=120,4

pH= 7.1 acidic

Why does fluid composition matter?

Because gradients are necessary for resting membrane potential, upstrokes of action potentials, excitation contraction coupling, and nutrient absorption.

What does the Gibbs-Donnan Equilibrium state?

Negatively charged plasma proteins cause redistribution of permeat ions which gives way to the Gibbs-Donnan ratio of ions in the plasma vs ions in the ICF.

Describe the cell membrane composition.

The cell membrane is composed of what is called a phospholipid bilayer. Phospholipids, which have a hydrophilic glycerol head and a hydrophobic fatty acid tail come together to create a bilayer that regulates passage of molecules and ions in and out of the cell.

Why do we have cell membranes?

To move the cell, communicate with other cells, protect the cell, separate the ICF and ECF, and to selectively transport material to different areas.

Why is the cell membrane considered to be a mosaic?

Because the many components that compromise it are free to move around. "Life rafts" of molecules in the cell will work together/move together.

What are the types of proteins found in the cell membrane?

Integral, transmembrane (ligand)]', and peripheral. Peripheral are attached via hydrostatic interactions, and thus are loose/capable of moving around membrane.

What are the three characteristics of carrier mediated transport?

1-Stereospecificity: The ability to differentiate between different chemical structures of a molecule, and thus reject isomers.

2- Saturation: Transporters have limited binding sites, so when full they may reach Tm (transport maximum)

3-Competition: Competing solutes have the potential to fill transporters.

What components does permeability depend on?

Partition coefficient

Diffusion coefficent

Thickness of the membrane

Surface area

Rate of net diffusion

Electrolytes

What are the two types of transport that move solutes downhill?

Simple and facilitated diffusion.

What is an example of facilitated diffusion?

D-Gluc being carried into skeletal muscle and adipose via the GLUT4 transporter.

What is the basis of simple diffusion with non electrolytes?

Random motion! Different factors such as membrane thickness, surface area of the membrane, permeability, and partition & diffusion coefficients effect rate. but it primarily is driven by the concentration gradient. (Relatively steady rate)

What is the basis of simple diffusion with electrolytes?

Still concentration gradient, however, chemical gradient can also effect rate. Like charges will repel like charges and thus slow down rate. The chem and concentration gradient may be additive in the rate, or they may cancel one another out.

What is primary active transport?

The movement of solutes against EC gradient, NEEDS ENERGY. Energy in the form of hydrolyzed ATP is what fuels this and helps keep the ICF and ECF

What are the types of transport pumps that move solutes uphill?

Primary and secondary active transport.

Describe primary active transport.

Transport that requires both a carrier and an energy source (ATP).

Describe what occurs in Na/K ATPase pumps.

Na/K pumps are found in EVERY cell but only do work specific to each cell.

3 molecules of sodium are transported out of the cell while 2 molecules of potassium are transported into the cell. This creates an electrogenic flow which creates a potential difference (more positive out than in)

During the E1 Alpha phase, 3Na binds, ATP is hydrolyzed, phosphate transfers to enzyme which starts E2 alpha phase, 2K bind as inorganic phosphate is released, ICF ATP binds.

Describe how cardiac glycosides effect the heart?

They act on the EC leaflet of the Na/K pump, which inhibits Na from leaving the cell. When the Na/K pump isn't working then the secondary active pumps such as Ca+ don't work either. Keeping Ca in the cell aims to increase HR.

What drug inhibits the Na/K pump by binding to the E2-P phase near the potassium binding site?

Cardiac glycosides

Describe the roles and process of the Ca2+ ATPase.

PMCA: Plasma membrane calcium pump that pumps one calcium out per ATP ---> maintains low Ca2+ in ICF

SERCA: SR/ER pump that helps pump excess Ca+ back into the SR/ER for storage.

Describe the roles and process of the H+/K+ ATPase

This pump is found in parietal cells lining the gastric mucosa. H+ is pumped into the cell to maintain the low pH of the stomach for digestion.

What pump does omeprazole inhibit?

The H+/K+ ATPase

What is an example of the secondary active transport process called cotransport?

Na/Glucose transporter SGLT1 found in the intestinal epithelium. Both move in the same direction, however sodium is working with its gradient and glucose against.

What is an example of the secondary active transport process called countertransport?

Ca/Na exchange that pumps Na in and Ca out of the cell. Opposite direction- Na move into cell with gradient created by Na/K pump, while Ca moves out uphill to create low Ca inside cell.

What is osmosis?

The flow of water due to solute concentration (pressure). Flow is due to presence of impermeat solutes. Water moves to area with less water!

What is osmolarity?

The concentration of particles in a solution (osmoles/L).

What is an osmole?

The number of particles in which a solute dissociates in a solution.

What is responsible for concentration differences ?

Energy consuming transport mechanisms that move items between the ICF and ECF in addition to the cell membrane.

What is osmotic pressure?

Solute difference can cause a pressure difference on each side of the semipermeable membrane. This is the pressure that would be required to STOP the flow of osmosis to the side with a higher solute concentration.

In an open system, all water would move freely, in a closed system, pressure differences impede osmosis.

What are the different meanings of the reflection coefficient found in the Vant Hoff Eq?

1.0= membrane impermeable such as serum albumin and IC proteins.

0= Membrane is freely permeable such as urea

0-1= most solutes are neither impermeable and neither impermeant so in-between!

Explain water flow and tonicity of a cell relative to osmotic pressure.

Water will flow from a hypotonic cell to a hypertonic cell.

Describe how Edema is an example of osmotic pressure/osmosis.

The protein in blood are osmotically active. When concentration in blood protein is lower than in the tissues, water from the blood flows into the tissues. Rupture of the tissue cells can also cause leakage of ICF into ECF.

Describe IV fluids and the results of various compositions.

It is normally isosmotic to prevent water flow, if it was hypertonic, the tissue water would flow into the blood, if it was hypotonic, the water would flow into the tissues. Lots of potentials for bad situations here.

What are some characteristics of ion channels?

Selective, gate controlled, conductance depends on probability of the channel being open, sensor controlled via changes in the membrane potential.

What are the three types of ion channels?

1-Voltage gated: Gates are controlled by changes in the membrane activation. Gates open when depolarized.

2-Nongated (leak channels)

3-Ligand gated- controlled by a conformational change initiated by a receptor when an NT or other substrate binds.

What is a diffusion potential?

The potential difference generated across a membrane when a charged solute diffuses down a concentration gradient. Caused by diffusion of ions. Magnitude and sign (+/-) of the molecule effect this. This electrical event also depends on the size of the gradient. (large Na influx, large dif potential).

What is the equilibrium potential?

The diffusion potential that exactly balances or opposes the tendency for diffusion of an ion down its concentration gradient.

What is electrochemical equilibrium?

When the chemical and electrical driving forces are equal and opposite such that no more diffusion occurs.

What three things effect the equilibrium potential?

Permeability, charge, and concentration.

What is the Nernst equation?

Describes the equilibrium potential across a membrane for a single ion via it's concentration. The equation converts concentration into a voltage.

What is the equilibrium potential for sodium? Potassium? RMP?

Na= +65mv

K=-85 mV

RMP= -70

What is the resting membrane potential? (RMP)

Normally is around -70-80 mV. Higher conductance means that molecules are driven TOWARDS their potentials.

Describe how ions play a role in maintaining the RMP

All ions play a role because each ion attempts to drive the membrane toward its equilibrium potential. Ions with the highest conductance/permeability will make the greatest contribution to the membrane potential.

What is responsible for the hyperpolarizing after potential?

The already high conductance of potassium becomes even higher than it is at rest.

What is the refractory period?

The time after completion of an AP where another AP cannot be elicited (due to voltage gated K+ channels)

What pump regulates the negative RMP?

Na/K ATPase. It does this by pumping (+) out and maintaining the K diffusion potential which drives the membrane toward the K eq potential. By convention, RMP is defined by the basis of the intracellular potential which is negative.

What is an AP?

A wave of excitability in a muscle/ nerve cell.

Describe the all or none concept for action potentials?

The threshold for Na is voltage gated so when the membrane hits a certain voltage all channels open.

Describe depolarization and inward currents.

To depolarize something is to make it LESS NEGATIVE.

Inward current is the flow of a positive charge into a cell to depolarize the membrane.

Describe hyperpolarization and outward flow.

To make the membrane more negative via outward flow of a positive ion.

What is the threshold potential?

The membrane potential at which an action potential is inevitable. This is normally less negative than the RMP so it's due to an inward current of (+).

What is overshoot?

An action potential where the membrane potential is positive or completely depolarized.

What are characteristics of action potentials?

Stereotypical curve shape, propagated, all or none.

What happens in the first step of an AP?

1. K+ is high conductance so it quickly diffusing out of the cell, this sets the RMP. (Different for different cells because other channels are also permeable to K+). Na channels are closed, and concentration is low.

What happens in the second step of an AP?

2. Na+ is low conduction so it is slowly diffusing into the cell UNTIL an inward current of Na via voltage gated channels, which causes an increase in Na+ conduction and creates an UPSTROKE.

What happens in the third step of an AP?

3. Upstroke is terminated by time/voltage channels closing. K channels open which results in outward current of K and repolarization.

What occurs in step four of an AP?

4. Basis for the undershoot; greating than resting condition of K following repolarization based on K channels being open.

Describe phase 0 in a ventricular cardiac myocyte's AP.

Upstroke is caused by Na permeability/ inward current.

Describe phase 1 in a VCM AP.

Initial depolarization due to outward current of K and cessation of inward sodium current.

Describe phase 2 in a VCM AP.

Plateau phase; inward Ca+ current and continued K outward balance.

Describe phase 3 in a VCM AP

Repolarization due to decrease in Ca+ permeability and reduction of inward current. Increase in K permeability greater than resting levels

Why is potassium's EQ potential closer to the RMP of a cell than sodium?

Because the cell has high conductance for potassium than it does for sodium when it is at rest.

How do AP's propogate?

The spread of local currents from active to inactive regions as positive charges in the cell move toward negative regions and depolarize them.

What is conductance?

This term refers to the permeability of a membrane. Membranes are selectively permeable to specific ions, classes of ions, size, cations, and anions.

What do tetrodotoxin and lidocaine block?

The Na (Tetro) and K (tetraethylammonium/lidocaine) channels thus preventing the occurrence of nerve action potentials.

Where does an AP start?

At the axon nearest the cell body.

What factors effect the travel time of the action potential?

Cable properties such as membrane resistance, membrane capacitance, and length. Myelination, an increase in nerve diameter, and saltatory conduction all INCREASE the travel time/ effectiveness of the action potential.

What is the condution velocity?

The speed at which an AP conducts along a nerve. This refers to the speed at which information can be delivered and is effected by myelination and the nodes of ranvier/saltatory conduction.

Why do we study physiology?

To be educated consumers and to have rationale for intervention.