Cell Physiology

what is a negative feedback mechanism?

it ensures homeostasis by reversing changes and maintaining variables within desired limits

what is a controlled variable?

a variable maintained within narrow normal limits to ensure system stability and balance

what are the roles of sensors and comparators?

sensors detect deviations from the set point

comparators evaluate the error signal to initiate corrective action

what is the effector response?

they act to restore the controlled variable back to the set point by opposing the stimulus causing deviation

what is the role of the plasma membrane?

regulates communication with the world outside of the cell

what is the role of the cytosol?

functions in signal and material transport and protein synthesis

what is the role of the nucleus?

houses DNA, DNA transcription

what are the roles of the endoplasmic reticulum and the golgi body?

protein processing and transport

what is the role of the mitochondria?

site of energy production and other metabolic processes

what is the role of the lysosome?

waste breakdown

what are the qualifications of the selective permeability of the phospholipid bilayer?

hydrophobic molecules freely pass through the membrane, while hydrophilic substances require protein channels or transporters`

what are the functions of membrane proteins?

they regulate cellular intake, signal transduction, and are targets for pharmacological agents

how do hydrophobic molecules cross the cell membrane?

they freely pass through the membrane, including steroid and thyroid hormones

how do hydrophilic molecules cross the cell membrane?

these and large molecules require protein channels or transporters to enter the cell

what types of drugs can cross the blood-brain barrier?

only hydrophobic drugs can cross, hydrophilic drugs remain peripheral

ex: antihistamines (cause drowsiness)

what are the characteristics of GLUT4 transporters?

they respond differently to insulin depending on isoform & it is insulin responsive (muscle, adipose tissue)

some diabetes drugs target glucose/sodium cotransporters (SGLTs)

what is the significance of cell polarity?

it involves distinct membrane compositions on different sides, critical for specialized functions like gut absorption and embryonic development

ex: gut epithelial cells have polarized membranes with unique protein expression on luminal and basal sides, essential for function

lactase is expressed only on the luminal side of gut epithelium, enabling digestion of lactose in the intestinal lumen

what is the role of the cytoskeleton?

it supports cell shape and transport with microtubules, microfilaments, and intermediate filaments, impacting mobility and disease diagnostics

what are the functions of cytosol processes?

they signal and support metabolism, protein synthesis, and intracellular transport

what are the drug targets in the cytoskeleton?

microtubules and targets for antimicrobial and anticancer therapies, affecting cell division and motility

how are signals from outside the cell relayed to their destinations?

initiate cytosolic signaling cascades

diffuse directly to the nucleus

diffuse to the cytosol and bind receptors → translocate to the nucleus together

what are the key metabolic pathways in the cytosol?

glycolysis, glycogen metabolism, pentose phosphate pathway, and fatty acid synthesis

where do protein and RNA processing occur?

protein translation occurs in the cytosol while RNA processing differs between nucleus and cytosol compartments

how are signals from outside the cell processed?

via cytosolic signaling cascades and receptor interactions

where does mRNA splicing and modification occur before export to the cytosol for translation?

in the nucleus

where does protein synthesis occur in the cell?

on ribosomes in the cytosol and rough endoplasmic reticulum for secretory proteins

what are the primary roles of the endoplasmic reticulum and the Golgi apparatus?

they process and traffic proteins to their functional destinations

what are the components of the cytoskeleton?

it consists of microtubules, microfilaments, and intermediate filaments that provide cell structure and transport pathways

what are the functions of the microtubules?

they are made of tubulin and act as highways for intracellular transport and support cell motility with cilia and flagella

what is the role of actin myofilaments?

they are crucial for muscle contraction and maintaining cell shape

what are the functions of the intermediate filaments?

they provide structural support and help identify cancer cell types through specific staining

they vary by cell type, which aids identification of different tissues

what is the function of the cilia and flagella in cells?

they are composed of microtubules and enable cell movement and environmental sensing

what is the clinical significance of microtubule dysfunction?

it causes disease and they are drug targets in cancer and infections

what processes happen inside the nucleus?

transcription factor interaction with and binding to DNA

DNA synthesis

RNA synthesis

what is the function of the nuclear membrane?

the double lipid membrane is porous and regulates transport of molecules in and out of the nucleus, maintaining cellular control

what is the organization of chromatin → chromosomes?

DNA in the nucleus is tightly wrapped around histone proteins forming chromatin which forms tightly coiled chromosomes to efficiently package genetic material

histone wrapped in DNA → chromatin coiled → chromosomes

what is epigenetics?

the study of genes and how the body knows which genes to activate, and how the environment affects it

what is the structure and function of the rough endoplasmic reticulum?

it is studded with ribosomes and serves as the main site of protein synthesis in the cell

where do proteins travel to following synthesis in the rough ER?

to the Golgi apparatus for modification and sorting

what is the clinical relevance to immunity of the rough ER and protein synthesis?

plasma cells have prominent rough ER to produce large amounts of antibodies (which are proteins) essential for immune response

what is the function of the Golgi apparatus?

it processes proteins after synthesis and tags them with biochemical signals for correct cellular destinations (transported on the cytoskeleton)

what is the importance of protein tagging?

post-translational modifications tag proteins to ensure proper trafficking and prevent disease

mistargeting proteins leads to diseases; drugs target cytoskeleton and membrane for therapeutic effects

what is the role of the Golgi apparatus in collagen synthesis?

it processes and modifies collagen proteins (many types) through multiple post-translational steps to ensure proper function

what is collagen’s role in health?

collagen synthesis is essential for tissue structure; defects lead to connective tissue disorders

what is the composition and osmolarity of the intracellular fluid?

it is the largest fluid compartment, rich in potassium and proteins, with consistent osmolarity around 285 mOsm

what is the composition of the extracellular fluid?

it contains high sodium levels, including interstitial fluid with no proteins

it is the “bath” for the cells

what is the composition and osmolarity of blood plasma?

it is a protein-containing fluid with balanced sodium, potassium, and chloride ions, maintaining osmolarity similar to other fluids

what is passive transport?

it requires no energy and includes simple and facilitated diffusion through the lipid bilayer or proteins, uses concentration differences (movement high → low)

what is active transport?

it uses energy to move molecules against concentration gradients via membrane-spanning proteins

what is vesicular transport?

it involves membrane vesicles to move large molecules by endocytosis and exocytosis

what are the two types of simple diffusion?

nonelectrolytes - movement only based on concentration difference

electrolytes - molecules that carry a small charge, so movement is dependent on concentration gradient and charge gradient (like charges repel)

what is facilitated diffusion (passive transport)?

no energy is required but another mechanism (car) is required due to the molecule’s size, but still based on concentration

what is primary active transport?

simple transport but requires ATP

what is secondary active transport and its types?

transport that indirectly uses ATP and uses concentration difference due to energy

cotransport

countertransport

what is “downhill” transport across the cell membrane?

no energy required (passive), traveling high to low on gradient; transport with an electrochemical gradient (caused by electrolytes and charged particles)

simple and facilitated diffusion

what is “uphill” transport across the cell membrane?

energy required (active); transport against an electrochemical gradient

primary (direct input) and secondary (indirect input) active transport

what does carrier-mediated transport require? and what are the specifications?

it requires an integral protein transporter

includes everything except simple diffusion

saturation: limited number of binding sites

stereospecificity: transports specific isomer

competition for the transporter

(aka vesicular transport)

what are the routes of passive transport?

it occurs via simple diffusion through lipid bilayers, channels, and facilitated diffusion through uniporters

only affected by concentration difference

what are the components of ion channels?

they have selectivity filters and gates that regulate ion passage based on size and charge

act as “gates” - some are always open, some are lock and key, based on charge

what are the kinetics of passive transport?

transport via uniporters is saturable and influenced by solute concentration and inactivation particles

facilitated diffusion rate is affected by concentration and number of transporters

what does simple diffusion of nonelectrolytes result from?

random thermal motion of molecules through a permeable membrane

continuous molecular movement in all directions; net diffusion from high concentration to low concentration

what is the net diffusion equation?

= flux = J in mmol/sec

where does the energy required for primary active transport come from?

ATP hydrolysis

ATP + H2O <=> ADP + Pi

what is primary active transport responsible for?

low intracellular Na+ and high K+ and low intracellular Ca2+

what is the Na+/K+ ATPase pump?

present on all cells (different types of pumps on different cell types)

3 Na+ out and 2 K+ in (causes an electrical difference, gives plasma membrane a voltage)

the Na+ binding site faces in and has a high affinity for Na+ while the K+ binding sites face out and has a high affinity for K+ (causes dumping of Na and K)

cardiac glycosides (digoxin) inhibit this pump to increase Ca2+ in cells

what is an electrogenic state at the Na/K pump?

a state where more positive is pumped out than pumped in, creating a potential difference

what is the Ca2+ ATPase pump?

pumps 1 Ca2+ from the intracellular side to the extracellular side of the cell

similar type of pump exists on the SR and ER, but 2 Ca2+ are transported

what is the H+/K+ ATPase pump?

on gastric and kidney cells

pumps H+ from the ICF into the lumen

what is secondary active transport?

it is linked to other mechanisms using ATP and something moves against a gradient

transport of two or more solutes is coupled where one usually moves uphill and the other downhill

energy comes from the downhill (i.e. ECF → ICF) movement of Na+ (generally), rather than ATP

secondary active because the Na+ gradient is maintained by the Na+/K+ ATPase pump (which itself uses ATP)

what is secondary active transport cotransport?

all solutes move in the same direction (co-), but one moves downhill and one moves uphill (along their concentration gradients)

Na+/glucose transporter: Na is moving ECF → ICF (downhill), glucose is moving ECF → ICF (uphill)

downhill via primary active transport with Na/K pump

uphill relies on Na/K pump energy from NA to go out even though it is uphill and can only work when [Na] is high in the cell

what is secondary active transport countertransport?

the solutes move in opposite directions, but one moves downhill and one moves uphill (along their concentration gradients)

ex: Na+ - Ca2+ exchange: Na+ moves ECF → ICF (downhill) and Ca2+ moves ICF → ECF (uphill)

what is osmosis?

the movement of water across a semipermeable membrane, from high water content to low water content

what is osmotic pressure?

the force per unit area required to stop water flow across the membrane caused by solute concentration differences

what is the reflection coefficient role?

it quantifies membrane permeability ranging from 0 (fully permeable) to 1 (completely impermeable) to solutes

what is osmolarity?

concentration of solutes in a single solution (solutes/volume of solution)

what are isosmotic solutions?

two solutions with equal osmolarity

what are the requirements for osmosis to occur?

there must be a concentration difference of solute across the membrane

membrane must be permeable to water, not solute

water, like particles flow from high concentration to low concentration

what is an isotonic solution?

a solution that has the same effective osmolarity as the cell and causes no net water movement (ECF is this as steady state with respect to the ICF because water moves freely across most cell membranes)

what is a hypotonic solution?

a solution that has a smaller effective osmolarity and causes cells to swell

what is a hypertonic solution?

a solution that has a larger effective osmolarity and causes cells to shrink

what are the factors that control the selectivity of ion channels?

selective based on size (of the channel) and charge

controlled by voltage or ligand-sensitive gates which open and close

what do ion channels “gate” (close) in response to?

changes in membrane potential (usually depolarization) (voltage-gated channels — generation and propagation of action potentials relies on this)

occupation of receptor (ligand-gated or receptor operated channels → the ligand can be a hormone or a neurotransmitter)

what is the permeability of ion channels to ions determined by?

number of open channels

selective permeability

• permeable to specific ions

• permeable to classes of ions (cations vs anions)

• permeable to a specific size of ion

what is resting membrane potential?

the voltage difference across a cell membrane when the cell is at rest, measured using microelectrodes (primarily determined by the Na/K pump)

what does diffusion potential arise from?

ion movement driven by concentration gradients, quantified by the Nernst equation involving KCl concentrations

what are electrochemical gradients in ion movement?

they combine electrical and chemical forces, determining ion movement and membrane voltage

what is diffusion potential?

it is the potential difference generated across a membrane when a charged solute (an ion) diffuses down its concentration gradient`

• caused by the diffusion of ions

• the magnitude is measured in mV, and depends on the size of the concentration gradient

• the sign (+ or -) depends on the charge of the diffusing ion

what is the equilibrium potential?

the diffusion potential that exactly balances or opposes the tendency for diffusion down the concentration difference

what is the electrochemical equilibrium?

the point at which the chemical and electrical driving forces acting on an ion are equal and opposite and no further net diffusion occurs

what are the factors that play a role in determining resting membrane potential?

all diffusible ions play a role

each permeant ion attempts to drive the membrane potential towards its equilibrium potential

ions with the highest permeability will make the greatest contributions to the membrane potential

what factors contribute to negative resting membrane potential?

the Na+/K+ ATPase pump (pumps out more positive than it brings in and maintains the K+ diffusion potential driving the membrane potential towards the K+ equilibrium potential

presence of nondiffusible negative charges inside the cell

resting membrane potential is defined on the basis of the IC potential (which is negative)

what is an action potential?

a wave of excitability that occurs in excitable cells (muscle and nerve)

basic mode of information transmission

what is depolarization?

the process of making the membrane potential less negative (-70 → 0)

inward currents, the flow of positive charge into the cell, depolarizes the membrane

what is hyperpolarization?

the process of making the membrane potential more negative

outward current, the flow of positive charge out of the cell, hyperpolarizes the membrane

what is threshold potential?

the membrane potential at which the occurrence of an AP is unavoidable

less negative than RMP so an inward current is needed to depolarize the cell

what is the overshoot?

the portion of the AP where the membrane potential is positive

what is the hyperpolarizing after-potential?

the part of the AP that is more negative than RMP

what is the refractory period?

the period of time after the completion of AP where another AP cannot be elicited

what are the defining characteristics of an AP?

stereotypical size and shape (in the same cell type) → all neurons, all cardiomyocytes

propagation, or spread

all or none principle → same voltage for all AP, no “small” AP

what is step 1 of the ionic basis for AP?

RMP is set by the high permeability to K+ (K+ channels are all open)

Na+ permeability is low (Na+ channels are closed)