structure and function of the renal tubule Flashcards
what are the 3 types of modification of ultrafiltrate in the tubule ?
filtration
reabsorption
secretion
happen in a continual exchange with the blood
what is reabsorption ?
movement of water and other solutes from the glomerular filtration to the blood
secretion is the movement in the opposite direction
what processes mediate reabsorption and secretion ?
Active Transfer/Primary Active Transport:
* Moving molecule/ion against conc gradient (low → high)
* Operates against electrochemical gradient
* Requires energy - driven by ATP
Passive Transfer (or flux):
* Passive movement down concentration gradient (requires suitable route)
* Important concept: removal of one component concentrates the other components
Co-transport/Secondary Active Transport:
* Movement of one substance down its concentration gradient generates energy allows transport of another substance against its concentration gradient
* Requires “carrier” protein
2 types: symport and antiport
describe transcellular transport
- movement of substances across both the luminal (apical) and basolateral membranes of epithelial cells.
- This process involves a combination of active and passive mechanisms.
Sodium-Glucose Cotransporter 2 (SGLT2):
* Located on the luminal side of the epithelial cells.
* It uses sodium (Na⁺) concentration gradients to actively transport glucose into the cell along with Na⁺.
* Mutations in SGLT2 can lead to Familial Renal Glycosuria, a condition where glucose is lost in urine despite normal blood glucose levels.
Sodium-Potassium Pump (Na⁺/K⁺ ATPase):
* Found on the basolateral membrane.
* Actively pumps 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell using ATP, maintaining low intracellular Na⁺ concentrations and creating a gradient for Na⁺ reabsorption.
Glucose Transport via GLUT2:
* Once inside the cell, glucose exits through GLUT2 transporters located on the basolateral membrane via facilitated diffusion.
Amino Acid Transport:
* Similar to glucose, amino acids are reabsorbed using sodium-dependent cotransporters on the luminal side and exit through specific transporters on the basolateral side.
what are the techniques used to investigate tubular functions ?
Clearance studies
Micropuncture & Isolated Perfused Tubule
Electrophysiological Analysis
Potential measurement
Patch clamping
1 = applied to man (observational)
2 & 3 = applied to lab animals (mechanistic)
describe micropuncture
describe electrophysiology
- Ion Movement: Ions like potassium, chloride, and calcium move in and out of cells, creating electrical signals (membrane potentials).
- Voltage Difference: The ion movement creates a voltage difference across the cell membrane, crucial for kidney functions like filtration and reabsorption.
- Measurement: Electrophysiology techniques use electrodes to measure this voltage and ion flow, helping scientists understand kidney cell function.
- Regulation: The electrical signals control kidney processes such as reabsorbing water and sodium, and secreting waste, important for fluid balance and blood pressure.
describe patch clamping
used to measure the electrical activity of individual cells or small regions of a cell’s membrane.
- Attach Pipette: A fine glass pipette is placed on the cell membrane.
- Form Seal: Suction is applied to create a tight seal between the pipette and membrane.
- Patch Isolation: A small patch of the membrane is pulled into the pipette.
- Measure Current: The electrical current (ion flow) through the membrane is measured.
- Study Ion Channels: The movement of ions through specific channels is observed and analyzed.
what are the 2 types of nephron ?
cortical nephron (85%) - short loop of henle - capillaries mainly around convoluted tubules
juxtamedullary nephron (15%) - long loop of henle - has specialised blood supply (vasa recta)
describe the proximal convoluted tubule
- Directly adjacent to Bowman’s capsule
- High capacity for reabsorption
Epithelial cell characteristics: - highly metabolic, numerous mitochondria for active transport
extensive brush border on luminal side - large surface area for rapid exchange
functions:
* THE MAJOR SITE OF REABSORPTION
* 65-70% of filtered load reabsorbed in proximal convoluted tubule
describe the segments of the loop of henle
- Thin Descending - very permeable to water
- Thin Ascending
Thin epithelial cells, No brush border, Few mitochondria, Low metabolic activity - Thick Ascending - impermeable to water , Na actively reabsorbed
Thick epithelial cells, Extensive lateral intercellular folding,
Few microvilli, Many mitochondria, High metabolic activity
what are the functions of the loop of henle ?
- Critical role in concentrating/diluting urine
- Adjusts rate of water secretion/absorption
describe what happens at the descending limb
- water reabsorption
- The descending limb is permeable to water but not to salts.
- As filtrate moves down the descending limb, it passes through a progressively more concentrated environment in the surrounding tissue (the medulla of the kidney).
- Water from the filtrate moves out of the tubule and into the surrounding interstitial space via osmosis, where the water is then picked up by nearby blood vessels (vasa recta).
- This causes the filtrate to become more concentrated as it moves deeper into the loop.
describe what happens at the ascending limb
- salt reabsorption
- The ascending limb is impermeable to water but actively transports sodium (Na+), chloride (Cl-), and potassium (K+) ions out of the filtrate into the surrounding tissue.
- This movement is accomplished by active transport mechanisms, such as the Na+/K+/Cl- cotransporter.
- As these salts are reabsorbed into the interstitial fluid, the filtrate becomes more dilute.
- The surrounding interstitial fluid in the medulla becomes more concentrated, which is crucial for the kidney’s ability to concentrate urine.
describe the counter current multiplier system
- the descending and ascending limbs of the loop work together in a process called the countercurrent multiplier system.
- This system creates a concentration gradient in the kidney, which allows for efficient reabsorption of water in the descending limb and salts in the ascending limb.
- The countercurrent flow helps maintain high concentrations of salts in the medulla, which is necessary for the kidney to concentrate urine.
what is the effect of the loop of henle on urine concentration ?
- The net result of the processes in the Loop of Henle is that the kidney can reabsorb water (via the descending limb) and salts (via the ascending limb) to regulate the body’s fluid balance.
- This also plays a crucial role in controlling the concentration of urine.
- In the distal nephron and collecting ducts, the final concentration of urine is adjusted based on the body’s hydration status, aided by hormones like antidiuretic hormone (ADH).
describe the early distal convoluted tubule
- Location of macula densa (juxtaglomerular apparatus)
- Provides feedback control of glomerular filtration rate & tubular fluid flow in the same nephron
- Relative straight (i.e. not the most convoluted bit of convoluted tubule)
what are the functions of the late DCT ?
- Solute reabsorption continues, w/out H2O reabsorption
- Further dilution of tubular fluid
- High Na+,K+-ATPase activity in basolateral membrane
- Very low H2O permeability
describe the collecting tubule
- Connects end of DCT to collecting duct – mainly in outer cortex
- Relatively straight in shape
- Overlap in functional characteristics with both late DCT and collecting duct
describe the collecting duct
- Collecting ducts formed by joining of collecting tubules
- Cuboidal-to-columnar epithelia, very few mitochondria
2 types of cells: - Intercalated cells
- Involved in acidification of urine and acid-base balance
- Principal cells
- Role to play in Na balance & ECF volume regulation
- Final site for processing urine
- Made very permeable to H2O by ADH
- Also permeable to urea
function:
* Reabsorbs Water: It takes water back into the body, especially when you’re dehydrated, with the help of the hormone ADH.
- Balances Salts: It adjusts levels of salts like sodium and potassium to keep the body in balance.
- Regulates pH: It helps keep the blood’s acidity at the right level by controlling how much acid or base is in the urine.
- Concentrates Urine: When needed, it makes urine more concentrated by reabsorbing water, helping the body conserve water.
how does ADH work ?
- Detection of Dehydration or Low Blood Volume: When the body is dehydrated (low water content) or the blood volume/pressure is low, sensors in the hypothalamus detect the change in blood osmolality (the concentration of dissolved substances, like salts). This triggers the release of ADH from the posterior pituitary.
- ADH Release into the Bloodstream: Once released, ADH travels through the bloodstream to the kidneys, specifically targeting the nephrons (the functional units of the kidney).
- Action on the Kidneys: ADH binds to receptors on the cells of the kidney tubules (specifically the collecting ducts). This binding increases the permeability of the collecting ducts to water by promoting the insertion of water channels called aquaporins into the cell membranes. This allows more water to be reabsorbed back into the bloodstream, rather than being excreted as urine.
- Conservation of Water: As a result, less water is lost in urine, and the urine becomes more concentrated. The body thus conserves water, helping to restore blood volume and osmolality to normal levels.
- Feedback Loop: Once the body has sufficient water or blood volume, or osmolality returns to normal, the hypothalamus detects this change and decreases the secretion of ADH, reducing water reabsorption by the kidneys, which leads to increased urine production and a return to a normal fluid balance.
describe diuresis and antidiuresis
Diuresis:
* Definition: Diuresis refers to the increased production and excretion of urine.
* What Happens: When the body needs to get rid of excess water or substances (like salts), the kidneys produce more urine. This can occur naturally, such as when you drink a lot of fluids, or due to the use of diuretic drugs.
* Example: Drinking a large amount of water will lead to diuresis as the kidneys work to excrete the excess water.
Antidiuresis:
* Definition: Antidiuresis refers to the reduced production of urine, where the body retains more water.
* What Happens: When the body needs to conserve water (like when you’re dehydrated), the kidneys reduce urine output. This is mainly controlled by the hormone ADH (antidiuretic hormone), which makes the kidneys reabsorb more water.
* Example: When you are dehydrated, your body produces more ADH, leading to antidiuresis. As a result, your urine becomes more concentrated, and you urinate less.
what are the Four Major factors contributing to build up of solute concentration in renal medulla ?
- Active transport of Na+ and co-transport of K+ & Cl- out of thick ascending limb into medullary interstitium
- Active transport of ions from collecting ducts into medullary interstitium
- Facilitated diffusion of large amounts of urea from collecting ducts into medullary interstitium
- Very little diffusion of water from ascending limbs of tubules into medullary interstitium
describe some kidney pathologies
