25-26 NURS1604 - Cellular transport (1), (2)_rev01

The Na+/Ca2+ exchanger (NCX) moves 3 Sodium ions (Na+) into the cell while simultaneously moving 1 Calcium ion (Ca2+) out of the cell.

The Na+/H+ exchanger (NHE) transports 1 Sodium ion (Na+) into the cell and 1 Hydrogen ion (H+) out of the cell.

The Chloride/Bicarbonate exchanger (AE) moves 1 Chloride ion (Cl-) into the cell and 1 Bicarbonate ion (HCO3-) out of the cell.

The cell membrane is primarily composed of a phospholipid bilayer that provides a barrier to water-soluble substances. Key features include:

• Fluidity: The membrane is flexible and can change shape.
• Selectivity: It selectively allows substances to enter or exit the cell.
• Proteins: Embedded proteins serve various functions, including transport, signaling, and structural support.
• Cholesterol: This component helps to stabilize membrane fluidity at varying temperatures.

Facilitated diffusion is crucial for the transport of polar molecules and ions across the cell membrane without energy expenditure. Its clinical significance includes:

• Drug Delivery: Many medications utilize facilitated diffusion to enter cells.
• Nutrient Absorption: Essential nutrients like glucose are absorbed via this mechanism.
• Pathophysiology: Impairments in facilitated diffusion can lead to conditions such as diabetes, where glucose transport is affected.

Active transport differs from passive transport mechanisms in that it requires energy (ATP) to move substances against their concentration gradient. Key differences include:

• Energy Requirement: Active transport requires energy, while passive transport does not.
• Direction of Movement: Active transport moves substances from low to high concentration, whereas passive transport moves from high to low concentration.
• Types: Active transport includes primary (direct use of ATP) and secondary (uses the energy from the electrochemical gradient).

Vesicular transport includes two main types: endocytosis and exocytosis. Their functions are:

These processes are essential for nutrient uptake, waste removal, and cell signaling.

The two types are:

1. Symport (cotransport): Two substances move across the membrane in the same direction.
2. Antiport (countertransport): Two substances move across the membrane in opposite directions.

The Na+/Cl- cotransporter (NCC) transports 1 Na+ ion and 1 Cl- ion into the cell.

The K+/Cl- cotransporter (KCC) transports 1 K+ ion and 1 Cl- ion out of the cell.

Na+ is more concentrated in the extracellular space than inside the cell.

Na+ is more concentrated in the extracellular space compared to the inside of the cell.

The Na+/phosphate cotransporter (NaPi IIa/b) transports 3 Na+ ions and 1 phosphate ion (P) into the cell.

The Na+/iodide symporter (NIS) transports 2 Na+ ions and 1 iodide ion (I-) into the cell.

The Na+/K+/Cl- cotransporter (NKCC) transports 1 Na+ ion, 1 K+ ion, and 2 Cl- ions into the cell.

The cell membrane is primarily composed of a phospholipid bilayer, which consists of:

• Phospholipids: Molecules with hydrophilic (water-attracting) heads and hydrophobic (water-repelling) tails.
• Proteins: Embedded within the bilayer, these can be integral or peripheral proteins that facilitate transport and communication.
• Cholesterol: Interspersed within the phospholipid bilayer, it helps to maintain membrane fluidity and stability.
• Carbohydrates: Often attached to proteins or lipids, they play a role in cell recognition and signaling.

The main types of cellular transport mechanisms include:

1. Diffusion: Movement of molecules from an area of higher concentration to an area of lower concentration.
2. Osmosis: The diffusion of water across a selectively permeable membrane.
3. Active Transport: Movement of molecules against their concentration gradient, requiring energy (ATP).
4. Vesicular Transport: Involves the transport of materials in vesicles, including endocytosis and exocytosis.

The clinical significance of cellular or transmembrane transport includes:

• Drug Delivery: Understanding transport mechanisms helps in designing drugs that can effectively enter cells.
• Disease Mechanisms: Abnormalities in transport proteins can lead to diseases, such as cystic fibrosis or diabetes.
• Therapeutic Targets: Transport proteins can be targeted for drug development to enhance or inhibit their function in disease treatment.

The cell membrane is composed of:

1. Phospholipid bilayers

   • Hydrophilic head:
     • One phosphate (-ve)
     • One hydrocarbon group (R), e.g., choline
     • One glycerol
   • Hydrophobic tails:
     • Two fatty acid chains

2. Transmembrane proteins (to be discussed later)

• Mainly embedded within phospholipid bilayers
• Examples include transport proteins (ion channels, protein carriers) and enzymes (usually near the cytoplasmic domain)

• Mainly located on the surface of phospholipid layers
• Can be either extracellular or intracellular
• Examples include receptors and antigens

The cell membrane is composed of a phospholipid bilayer with hydrophilic heads facing outward and hydrophobic tails facing inward. It contains various embedded components such as intrinsic proteins, extrinsic proteins, cholesterol, glycoproteins, and glycolipids.

Intrinsic proteins, such as ion channels, span the entire membrane and facilitate the transport of ions and molecules across the membrane, contributing to cellular communication and homeostasis.

The hydrophilic heads of phospholipids orient towards the extracellular fluid and cytoplasm, while the hydrophobic tails face inward, creating a bilayer that serves as a barrier to most water-soluble substances, thus maintaining the integrity of the cell.

Cholesterol molecules are interspersed within the phospholipid bilayer, providing stability and fluidity to the membrane, which is essential for proper cell function and integrity.

Glycoproteins and glycolipids play crucial roles in cell recognition, signaling, and adhesion. They are involved in interactions with other cells and the extracellular environment, contributing to the overall functionality of the cell membrane.

The cell membrane is selectively permeable, meaning it only allows certain types of molecules to directly pass through the phospholipid bilayers based on specific criteria.

The criteria for molecules to pass through the phospholipid bilayer are:

1. Small and non-ion molecules
2. Lipid-soluble molecules

Ions cannot directly travel across the cell membrane due to the following reasons:

1. Charge: Ions are charged particles (either positive or negative), and the cell membrane is composed of a phospholipid bilayer that is hydrophobic (water-repelling). This hydrophobic nature prevents charged ions from passing through without assistance.

2. Size: Ions are often too large to pass through the small pores in the membrane that are designed for smaller, uncharged molecules.

3. Transport Proteins: Ions require specific transport proteins (such as channels or carriers) to facilitate their movement across the membrane. These proteins provide a pathway for ions to move in and out of the cell, overcoming the barrier posed by the lipid bilayer.

1. Simple diffusion: Movement of molecules directly through the membrane without assistance.
2. Facilitated diffusion: Movement of molecules across the membrane via specific transmembrane proteins.
   Both types are passive processes, meaning they do not require energy and occur down the concentration gradient.

Osmosis is defined as the diffusion of water across a selectively permeable membrane. It is a specific type of diffusion that focuses on the movement of water molecules, typically occurring from an area of lower solute concentration to an area of higher solute concentration.

1. Primary active transport: Directly uses ATP to transport molecules against their concentration gradient.
2. Secondary active transport: Uses the energy from the movement of one molecule down its gradient to drive the transport of another molecule against its gradient.
   Both types require energy and move substances against the concentration gradient.

1. Endocytosis: The process by which cells internalize substances from their external environment.
2. Exocytosis: The process by which cells expel substances to the external environment.
   Both methods involve the transport of large molecules or particles in vesicles.

1. Small & non-ion molecules
2. Lipid-soluble molecules (e.g., Vitamin A, D, E, K)

Gases (e.g., oxygen, carbon dioxide) and fat-soluble vitamins can diffuse directly through the plasma membrane.

Simple diffusion is the process by which molecules move from an area of higher concentration to an area of lower concentration. It occurs not only across the cell membrane but also within the cell, contributing to the formation of intracellular electric currents.

Lipid-insoluble substances such as glucose, amino acids, and ions utilize facilitated diffusion to cross the cell membrane.

The two main types of proteins involved in facilitated diffusion are:

1. Protein channels - allow ions to move through the membrane.
2. Protein carriers - bind to specific molecules (like glucose) and transport them across the membrane.

Ion channels facilitate ion transport by allowing ions to move down their concentration gradient. This process occurs through the following mechanisms:

1. Concentration Gradient: Ions move from areas of higher concentration to areas of lower concentration, creating an influx of ions into the cell.

2. Channel Structure: The structure of ion channels is specifically designed to allow certain ions to pass while blocking others, ensuring selective permeability.

3. Electrical Gradient: The movement of ions also depends on the electrical gradient across the membrane, influencing the direction and speed of ion flow.

4. Intracellular Current: The influx of ions generates an intracellular current, which can affect cellular functions and signaling processes.

Calcium (Ca²⁺) channel blockers, such as diltiazem and verapamil, are anti-anginal drugs that reduce intracellular Ca²⁺ levels. This leads to weakened cardiac contraction, which decreases the heart's demand for blood, making them effective in managing angina.

Sodium (Na⁺) channel blockers, like flecainide and propafenone, are classified as anti-arrhythmic drugs (class Ic). They inhibit Na⁺ influx, which reduces the intracellular Na⁺ current, thereby affecting electrical conduction across the heart and influencing heart rate.

Water moves from areas of high water potential (or low osmolarity) to areas of low water potential (or high osmolarity).

Water moves much faster through aquaporins compared to the very slow movement directly through the lipid bilayer.

Higher water potential indicates a greater concentration of water molecules relative to solute molecules. This results in lower osmolarity because osmolarity is defined as the concentration of solute particles in a solution. Therefore, as water potential increases (more water, fewer solutes), osmolarity decreases.

The relationship is inversely proportional: as water potential increases, osmolarity decreases. This is because water potential is a measure of the potential energy of water in a system, while osmolarity measures the concentration of solutes. A higher concentration of solutes leads to a lower water potential.

Osmotic flow develops across the cell membrane due to the following reasons:

• The cell membrane is selectively permeable, allowing only certain substances to pass through.
• Solute molecules (ions) cannot directly travel across the membrane.
• Water molecules are attracted to solutes, leading to movement towards regions with higher solute concentration (higher osmolarity).

Osmotic flow occurs from regions of low osmolarity to regions of high osmolarity.

• More concentrated solute leads to an increase in osmolarity.
• An increase in osmolarity results in an increase in osmotic pressure.

An isotonic solution is one that has the same osmolarity as a cell, meaning there is no net movement of water into or out of the cell.

A hypertonic solution is characterized by having a higher osmolarity than a cell, which can lead to water moving out of the cell, causing it to shrink.

A hypotonic solution is defined as having a lower osmolarity than a cell, resulting in water moving into the cell, which can cause it to swell or even burst.

When an isotonic solution is infused into the ECF, there is no net movement of water between the ICF and ECF. The osmolarity remains balanced, and the volume of ICF remains unchanged.

Infusing a hypertonic solution into the ECF causes water to move out of the ICF into the ECF to balance the osmolarity. This results in a decrease in the volume of ICF, leading to cellular shrinkage.

When a hypotonic solution is infused into the ECF, water moves from the ECF into the ICF to equalize osmolarity. This causes an increase in the volume of ICF, potentially leading to cellular swelling or even lysis if the influx is excessive.

Ion pumps, also known as ATPases, enzymatically break down ATP to release an energetic phosphate (PO43-), which is essential for transporting ions against their concentration gradient.

The different types of ion pumps include:

1. P-type: Activated by phosphorylation; examples include Na+/K+ ATPase, Ca2+, and Mg2+.
2. V-type: H+ ATPase found in vesicles/vacuoles, such as lysosomes.
3. F-type: H+ ATPase located in the mitochondrial inner membrane.
4. ABC transporters: ATP binding cassette transporters, including P-glycoprotein and CFTR (cystic fibrosis transmembrane conductance regulator).

1. Binding of cytoplasmic Na+ to the pump protein stimulates phosphorylation by ATP.

2. Phosphorylation causes the protein to change its shape.

3. The shape change expels Na+ to the outside, and extracellular K+ binds.

4. K+ binding triggers the release of the phosphate group.

5. Loss of phosphate restores the original conformation of the pump protein.

6. K+ is released and Na+ sites are ready to bind Na+ again; the cycle repeats.

The Na+/K+ ATPase pumps 3 Na+ ions out of the cell and 2 K+ ions into the cell. This results in:

• Extracellular region having more Na+ ions.
• Intracellular region having more K+ ions.
• The intracellular region loses more positive ions than it gains, leading to a net negative charge inside the cell compared to the outside.

When the Na+ channel is opened, Na+ ions move into the cell. This influx of Na+ ions contributes to depolarization of the cell membrane.

The movement is driven by the electrochemical gradient of another substance, often Na⁺ ions.

Na⁺/K⁺ ATPase creates a higher concentration of Na⁺ ions extracellularly and a lower concentration intracellularly, facilitating secondary active transport.

The Na+/glucose cotransporter (SGLT1) transports 2 Na+ ions and 1 glucose molecule into the cell, utilizing the sodium gradient for glucose uptake.

SGLT1 (sodium glucose co-transporter-1) facilitates the transport of D-glucose and D-galactose from the lumen of the intestinal tract into the intestinal epithelial cells by co-transporting them with 2Na+ ions. This process is crucial for glucose absorption in the intestines.

Sotagliflozin acts as an inhibitor of SGLT1, thereby reducing the transport of D-glucose and D-galactose into intestinal epithelial cells. This inhibition can lead to decreased glucose absorption and is significant in the management of diabetes.

In addition to SGLT1, other transport proteins include:

1. GLUT5 - transports D-fructose.
2. GLUT2 - transports D-glucose, D-galactose, and D-fructose.
3. Na-K-ATPase - transports 3Na+ ions out of the cell and 3K+ ions into the cell, maintaining the electrochemical gradient necessary for SGLT1 function.

Phagocytosis, also known as 'cell eating', is a type of endocytosis that involves the uptake of solid molecules, such as bacteria.

Pinocytosis, referred to as 'cell drinking', is a type of endocytosis that involves the uptake of dissolvable molecules, such as DNA, protein, and fat droplets.

Receptor-mediated endocytosis is a process where specific molecules are taken up when recognized by specific receptors, such as cholesterol.

Phagocytosis is a type of endocytosis where a cell engulfs large particles, such as bacteria. The cell membrane extends outward to form a structure called Pseudopodium around the particle. Once the particle is fully enclosed, it forms a Phagosome within the cell, allowing for digestion and processing of the engulfed material.

Pinocytosis is a form of endocytosis that involves the uptake of liquid containing small solutes, such as DNA or Protein. Unlike phagocytosis, which engulfs large particles, pinocytosis involves the invagination of the cell membrane to form a Vesicle that contains the liquid, allowing for nutrient absorption.

In receptor-mediated endocytosis, specific molecules, such as Cholesterol, bind to Receptor proteins on the cell membrane. This binding triggers the invagination of the membrane, aided by Coat proteins, leading to the formation of a Coated vesicle that contains the bound molecules and receptors, facilitating selective uptake.

LDL receptors recognize LDL (low density lipoprotein) and facilitate the uptake of cholesterol into cells, particularly in the liver and peripheral tissues.

PCSK9 inhibitors increase the number of LDL receptors in the liver, leading to enhanced liver uptake of cholesterol and a decrease in LDL/cholesterol levels in the blood.

Exocytosis is the process of secretion of large molecules from a cell as vesicles. Like endocytosis, it requires energy for the transport of these vesicles to the cell membrane where they fuse and release their contents into the extracellular fluid.

An example of exocytosis is the release of hormones or neurotransmitters from cells. In this process, secretory vesicles containing these molecules move to the cell membrane, fuse with it, and release their contents into the extracellular space.