Membrane Transport Mechanisms

Random movement of molecules across a membrane, driven by kinetic energy.

Movement of molecules against their concentration gradient, requiring energy.

Movement of large molecules with the help of carrier proteins across a membrane.

Movement of small, lipid-soluble molecules directly across the membrane, without help from proteins.

Molecule movement down the concentration gradient, no energy required.

Difference in concentration of a substance across a membrane.

Process of taking in liquids or small molecules from the environment.

Membrane proteins that bind and transport specific substances across membranes.

The movement of molecules from a region of high concentration to a region of low concentration, due to random thermal motion.

The more lipid-soluble a molecule is, the faster it will diffuse across a cell membrane.

Movement of molecules against their concentration gradient, using energy directly from ATP hydrolysis.

Movement of molecules against their concentration gradient, using energy from another molecule's movement down its gradient.

A membrane protein that moves two molecules in opposite directions across a membrane.

The combined force driving the movement of ions across a membrane, considering both concentration and charge differences.

The diffusion potential across a membrane that exactly opposes the net diffusion of a particular ion.

It describes the rate of diffusion of an electrically neutral solute across a membrane, considering factors like concentration gradient and lipid solubility.

The flux, which measures how fast a solute X moves across the membrane.

The lipid-water partition coefficient (Kp) of a solute determines how easily it dissolves in the membrane's lipid bilayer.

A measure of how easily a substance can pass through a membrane. It takes into account the membrane's thickness, the substance's lipid solubility, and the substance's size.

Indicates how easily a substance dissolves in lipids compared to water. A high Kp value means the substance is more lipid-soluble, while a low Kp value indicates greater water solubility.

The logarithm (base 10) of the lipid-water partition coefficient (Kp). Used to express a drug's lipid solubility more conveniently, especially for large differences.

The process where a drug molecule gains or loses a proton (H+), forming charged ions. This can influence its ability to cross cell membranes.

The pH value at which a drug is 50% ionised and 50% un-ionised. It reflects the drug's tendency to ionise.

A drug's ionisation state is influenced by the pH of its environment. Drugs can become 'trapped' in compartments with a different pH compared to where they started.

The movement of substances across cell membranes with the help of specific protein carriers.

A protective barrier between the blood and the brain, formed by specialized cells that restrict the passage of many substances.

The digestive tract, where food is broken down and nutrients are absorbed.

The organ that connects a developing fetus to the mother's uterus and provides nutrients and oxygen.

Part of the kidney where waste products are filtered and reabsorbed.

The pathway that carries bile from the liver to the gallbladder and small intestine.

When there are too many molecules to be transported at once, the rate of transport reaches a maximum and cannot increase further.

The concentration of a solute at which the rate of transport is half its maximum (Vmax). Indicates the affinity of the transporter for the solute.

A family of carrier proteins that facilitate the transport of glucose across cell membranes in various tissues.

Specialized proteins in the cell membrane and intracellular organelles that actively transport calcium ions (Ca2+) against their concentration gradient, using energy from ATP hydrolysis.

Programmed cell death, a process that eliminates unwanted or damaged cells. Excessive calcium signaling can trigger apoptosis.

Energy derived directly from ATP hydrolysis is used to move protons (H+) against their concentration gradient.

Parietal cells in the stomach use primary active transport to secrete H+ ions, forming hydrochloric acid (HCl) for digestion.

Specialized intercalated cells in the kidneys actively secrete H+ into the urine to maintain blood pH balance.

Energy from the movement of Na+ down its concentration gradient is used to move other molecules against their concentration gradient.

Sodium (Na+) and glucose bind to a carrier protein at the intestinal lining. The energy from Na+ moving into the cell drives glucose uptake.

Similar to Na+/glucose, Na+ movement drives the uptake of amino acids into cells, essential for building proteins.

A protein in the cell membrane that exchanges sodium ions (Na+) for protons (H+), impacting both pH balance and sodium transport.

Different types of Na+/H+ exchangers found in various locations within cells, each with a specific role in pH and sodium regulation.

Sodium ions (Na+) move into the cell while calcium ions (Ca2+) move out, using the same carrier protein.

Diarrhea can be caused by reduced NaCl absorption in the intestines, often due to increased cAMP or cGMP levels altering transporter activity.

Medications that block the Na+/Cl- symporter in the distal convoluted tubule, decreasing sodium and chloride reabsorption and increasing urine output.

Thiazide diuretics block the Na+/Cl- symporter in the distal convoluted tubule, causing increased sodium, chloride, and water excretion in the urine.

Used to treat hypertension, mild heart failure, oedema, to prevent kidney stones, and nephrogenic diabetes insipidus.

Common side effects include hypokalaemia, hypocalciuria, increased urination, and potential interactions with other drugs.

Thiazides increase potassium excretion due to several mechanisms, including activation of the renin-angiotensin-aldosterone system (RAAS) and hypochloraemic alkalosis.

Thiazides can worsen gout by reducing uric acid excretion, leading to increased uric acid levels in the blood.

Thiazides can increase the risk of digoxin toxicity by increasing intracellular sodium, which enhances digoxin's effect on the Na+/K+ ATPase pump.

Thiazides can reduce urine volume in diabetes insipidus by interfering with the production of hypotonic fluid in the distal tubule.

Thiazides increase the activity of the Na+/Ca2+ antiporter on the basolateral membrane, leading to increased calcium transport into the interstitium.

Thiazides are contraindicated in patients with hypotension, gout, renal failure, lithium therapy, hypokalaemia, and can worsen diabetes.

The portion of the nephron where sodium and chloride ions are reabsorbed from the filtrate, leading to a more dilute filtrate as it ascends.

The section of the nephron where selective reabsorption and secretion of ions like sodium, chloride, and bicarbonate occur to maintain blood pH and electrolyte balance.

The final part of the nephron where water and solutes are reabsorbed from the filtrate, forming dilute urine.

Diuretics increase the excretion of sodium and water by decreasing the reabsorption of sodium and chloride from the filtrate in the nephron.

Diuretics can act directly on cells of the nephron or indirectly by modifying the content of the filtrate, ultimately reducing sodium and chloride reabsorption.

A class of diuretics that inhibit bicarbonate reabsorption in the proximal tubules, leading to mild diuretic effect.

They primarily target the PCT which only accounts for a portion of sodium reabsorption. Other portions of the nephron can compensate for the loss, leading to reduced diuretic effect compared to other classes.

Diuretics that work in the proximal tubules, loop of Henle, and collecting duct by inhibiting water and sodium reabsorption.

Potent diuretics that inhibit sodium, potassium, and chloride reabsorption in the thick ascending limb of the loop of Henle.

Diuretics that act in the early distal tubule by inhibiting sodium and chloride co-transport.

Diuretics that work in the late distal tubule and collecting duct by inhibiting sodium reabsorption and potassium secretion.

They target the thick ascending limb of the loop of Henle, blocking the Na+/K+/2Cl- co-transporter, leading to increased sodium and chloride excretion in urine.

Loop diuretics are used to treat fluid overload conditions like heart failure, edema, hypertension, and renal failure.

They can increase the excretion of calcium and magnesium, decrease uric acid excretion, and have vasodilatory effects.

Drugs like spironolactone and eplerenone that block the action of aldosterone in the kidneys.

Aldosterone stimulates sodium reabsorption and potassium secretion in the distal tubules and collecting ducts of the kidney.

They competitively bind to aldosterone receptors, preventing aldosterone from stimulating sodium reabsorption and potassium secretion.

They reduce sodium retention and potassium excretion, leading to increased potassium in the blood.

Used to prevent potassium loss caused by other diuretics and to treat hypertension and heart failure.

They can cause high potassium levels in the blood (hyperkalemia) which can be dangerous.

Drugs like amiloride and triamterene that block sodium channels in the kidney.

They block the epithelial sodium channel (ENaC) in the collecting tubules, reducing sodium reabsorption and potassium excretion.

They are used with loop diuretics and thiazides to help prevent potassium loss and maintain potassium balance.

When two or more drugs, food, beverage, or supplements interact with each other, potentially changing their effects.

Drug-drug, drug-food, and drug-condition interactions.

Low potassium levels (hypokalaemia) can increase the risk of digoxin toxicity, leading to heart rhythm problems.

Loop diuretics can worsen hypokalaemia, increasing the risk of digoxin toxicity.

NSAIDs can reduce the effectiveness of thiazides by affecting their action in the kidneys.

These drugs combined can significantly increase potassium levels in the blood, potentially leading to dangerous heart rhythm problems.

The Na+/H+ exchanger in the proximal convoluted tubule (PCT) facilitates the reabsorption of sodium (Na+) into the bloodstream. It exchanges sodium from the filtrate for hydrogen ions (H+) secreted into the lumen, ultimately contributing to the acidic environment of the PCT.

Antiport systems are membrane transport proteins that move two different molecules in opposite directions across a membrane. They are coupled processes, meaning the movement of one molecule is dependent on the simultaneous movement of another in the opposite direction.

Bicarbonate (HCO3-) is completely reabsorbed in the PCT. This process involves proteins converting filtered bicarbonate into carbonic acid (H2CO3), which then dissociates into carbon dioxide (CO2) and water (H2O). CO2 diffuses passively across the PCT epithelium and is reabsorbed into the blood.

Carbonic anhydrase, an enzyme present in the PCT, plays a crucial role in bicarbonate reabsorption. It catalyzes the conversion of carbonic acid (H2CO3) into carbon dioxide (CO2) and water (H2O), enabling the efficient reabsorption of bicarbonate.

The interstitial fluid of the medulla is hypertonic due to the active reabsorption of sodium chloride (NaCl) from the thick ascending limb of the loop of Henle, without a corresponding reabsorption of water. This creates a concentration gradient, making the interstitial fluid more concentrated than the tubular fluid.

The NKCC2 symporter, found in the thick ascending limb of the loop of Henle, is a protein that actively transports sodium (Na+), potassium (K+), and chloride (Cl-) into the cell from the tubular lumen. This movement is fueled by the electrochemical gradient created by the sodium-potassium pump.

The descending limb of the loop of Henle is highly permeable to water. As the interstitial fluid of the medulla becomes hypertonic due to the countercurrent concentrating system, water passively reabsorbs from the descending limb into the interstitial fluid, increasing the osmolality of the filtrate.

Antidiuretic hormone (ADH) plays a crucial role in controlling urine concentration. When ADH is present, it increases the permeability of the collecting duct to water. This allows more water to be reabsorbed into the bloodstream, resulting in concentrated urine.

The early distal tubule further dilutes the tubular fluid by reabsorbing sodium chloride (NaCl) while maintaining impermeability to water. This action helps maintain the concentration gradient established in the loop of Henle.

The sodium-potassium pump (Na/K ATPase) in the basolateral membrane of the distal tubule actively pumps sodium out of the cell. This creates a concentration gradient that drives sodium to enter the cell from the lumen, accompanied by chloride.

Intercalated cells in the collecting tubule are responsible for regulating the acid-base balance of the urine. Type A intercalated cells secrete hydrogen ions (H+) into the lumen, while Type B cells secrete bicarbonate (HCO3-) into the lumen.

Principal cells, found in the collecting duct, are responsible for the reabsorption of sodium (Na+) and the secretion of potassium (K+) under hormonal control. They also contribute to the regulation of water reabsorption.

Aldosterone, a hormone produced by the adrenal glands, plays a key role in regulating sodium and potassium balance. It promotes sodium reabsorption and potassium excretion by acting on the principal cells of the collecting duct.

Antidiuretic hormone (ADH) acts on the collecting duct to increase its permeability to water. This allows for the passive reabsorption of water from the tubular fluid into the interstitial space, ultimately resulting in the production of concentrated urine.

The glomerulus is a network of capillaries responsible for filtering small solutes from the blood. It acts like a sieve, allowing small molecules to pass through but retaining larger molecules and blood cells.

Loop diuretics like furosemide block the Na+, K+, 2Cl- cotransporter (NKCC2) in the thick ascending limb of the loop of Henle, preventing the reabsorption of these ions and leading to increased excretion in urine.

Besides diuresis, loop diuretics increase calcium and magnesium excretion, decrease uric acid excretion, and can have vasodilatory effects.

Thiazide diuretics like hydrochlorothiazide inhibit the Na+/Cl- symporter in the early distal convoluted tubule, blocking the reabsorption of sodium and chloride ions.

Thiazides are preferred for treating uncomplicated hypertension and are used for congestive heart failure, edema, preventing kidney stones, and nephrogenic diabetes insipidus.

Potassium-sparing diuretics like spironolactone act on the late distal tubule and collecting duct by blocking the action of aldosterone, reducing sodium reabsorption and potassium excretion.

A condition with a high level of potassium (K+) in the blood, often caused by medications like potassium-sparing diuretics or decreased kidney function.

A state of decreased blood volume, often caused by excessive fluid loss due to conditions like diarrhea, vomiting, or diuretics.

A condition with low potassium levels in blood, often due to diuretics, certain diseases, or inadequate potassium intake.

A condition where the blood is too alkaline (high pH), often caused by excessive loss of acid (like hydrogen ions) in the kidney.

It helps regulate cell volume by pumping out more sodium ions (Na+) than potassium ions (K+), making the cell interior less attractive to water and preventing swelling.

To maintain a normal electrochemical gradient of sodium and potassium across the cell membrane, essential for cell function.

It uses the energy stored in the sodium gradient to drive the transport of other molecules, like sugars and amino acids, against their concentration gradient.

It is composed of an alpha subunit, which binds sodium, potassium, and ATP, and a beta subunit, which anchors the complex to the membrane and performs other regulatory functions.

The pump cycles through several steps, starting with binding sodium and ATP, then phosphorylating itself, changing conformation to release sodium and bind potassium, finally dephosphorylating and returning to its initial state, releasing potassium.

The pump exists in two main conformations: E1 with high affinity for sodium and low affinity for potassium, and E2 with low affinity for sodium and high affinity for potassium. These transitions allow for efficient ion transport.

Phosphorylation by ATP activates the pump, triggering a conformational change, while dephosphorylation allows it to return to its original state.

Ouabain is a toxin that inhibits the pump by blocking the dephosphorylation step, preventing the pump from returning to its original state and halting transport.

The pump can operate in five modes, including its normal mode, reverse mode (synthesizing ATP), and various exchange modes, depending on the electrochemical gradients and presence of specific ions.

The alpha subunit is the catalytic core, binding ions and ATP, while the beta subunit anchors the complex and performs regulatory functions. The gamma subunit is a small auxiliary protein with different functions.

Different tissues have specific requirements for sodium and potassium regulation, leading to the evolution of various isoforms with slightly different properties and sensitivity to inhibitors.

Digoxin inhibits the Na+/K+ pump, increasing intracellular sodium concentration, which indirectly leads to increased calcium levels and stronger heart contractions.

These are ATP-dependent transporters that pump drugs out of cells, contributing to multidrug resistance, making certain therapies ineffective.

Indirectly, it helps maintain calcium levels by creating a sodium gradient that powers the Na+/Ca2+ exchanger, which pumps calcium out of the cell.

It maintains cell volume, regulates electrochemical gradients, drives secondary transport, and influences calcium homeostasis, playing a vital role in various physiological processes.