Structure and Function Of Renal Tubule Flashcards
What are several techniques to investigate tubular function?
- clearance studies
- micropuncture and isolated perfused tubule
- electrophysiological analysis
Describe how electric potential is used to investigate tubular function (electrophysiological analysis).
- Alter potential difference (PD).
- Measure whether an ion is moving with or against the electrochemical gradient
Describe how patch clamping is used to investigate tubular function (electrophysiological analysis).
- Current flow through an individual ion channel is measured.
- Measure electrical resistance across a patch of the cell membrane.
- Changes when the channel opens or closes.
→ A blunt tip pipette is pressed against the cell membrane
What are the two types of nephrons?
Cortical and juxta-medullary nephrons
What is the difference between cortical and juxta-medullary nephrons?
- Cortical nephrons have a shorter loop of Henle
- Cortical nephrons make up a larger proportion of nephrons
In terms of reach loops, what is the difference between cortical and juxta-medullary nephrons?
- Cortical nephrons have short-reach loops that penetrate the boundary between the inner and outer zones of the medulla.
- Loops do not extend into the medulla.
- Juxtamedullary nephrons have long-reach loops that penetrate deep into the medulla (so they are better at concentrating urine).
In terms of blood supply, what is the difference between cortical and juxta-medullary nephrons?
- Entire tubular system of cortical nephrons surrounded by extensive capillary network.
- Long, efferent arterioles of juxtamedullary nephrons extend from the glomeruli to the outer medulla and divide into specialised capillaries that extend downwards into the medulla and lie side by side with the Loops of Henle.
RECAP: what are the functions of the PCT (proximal convoluted tubule)?
Major site for reabsorption
RECAP: Where is the PCT found?
Adjacent to the Bowman’s Capsule.
RECAP: How is the PCT adapted for reabsorption? Explain why it has these adaptations
- highly metabolic, numerous mitochondria - active transport
- extensive brush border on luminal side - large surface area for rapid exchange
What syndrome is associated with a defective PCT?
Fanconi’s Syndrome
What are the three segments of the loop of Henle?
- Thin Descending segment - permeable to water
- Thin Ascending segment - not permeable to water
- Thick Ascending segment - not permeable to water
Describe the structural features of the thin ascending segment.
- Thin epithelial cells
- No brush border
- Few mitochondria and low metabolic activity
Describe the structural features of the thick ascending segment.
- Thick epithelial cells
- Extensive lateral intercellular folding
- Few microvilli
- Many mitochondria for high metabolic activity.
RECAP: what are the functions of the Loop of Henle?
- Concentrating/ diluting urine.
- By adjusting the rate of water secretion/ absorption.
Describe the Medullary Osmotic Gradient.
- The Loop of Henle creates an osmolality gradient in the medullary interstitium.
- Collecting duct transverses the medulla
- Urine is concentrated as water moves out by osmosis.
Describe the vasa recta.
Capillaries that flow in parallel to the Loops of Henle
- Delivers O2 and nutrients to the cells of the Loop of Henle
Why is the setup of the blood flow to the medulla significant?
Maintain the osmotic gradient
What is the vasa recta permeable to? Why is this significant?
- Permeable to both H2O and salts
- Could disrupt the salt gradient established by the Loop of Henle.
How does the vasa recta avoid disrupting the salt gradient established by the Loop of Henle?
By acting as a countercurrent multiplier system
What happens when the vasa recta descends into the renal medulla? What happens when it ascends? What is the significance of this?
- Water diffuses out into the surrounding fluids, and salts diffuse in
- Reverse for when vasa recta ascends
- Salt in the vasa recta is always the same
- Salt gradient established by the Loop of Henle remains in place.
Why is water removed by the vasa recta?
Doesn’t dilute the longitudinal osmotic gradient
What is the importance of medullary blood flow in the vasa recta being slow?
- Sufficient to supply the metabolic needs of the tissue
- Minimise solute loss from the medullary interstitium.
What happens with the reabsorbed Na+ in the descending vasa recta?
- Carried to the inner medulla
- Equilibrates with the ISF
- Increases regional osmolarity.
What happens with the Na+ in the ascending vasa recta?
Returns to the systemic circulation
What is the amount of solute in ascending vasa recta the product of?
Flow rate and concentration
What happens when blood flow in the vasa recta increases?
Solutes are washed out of the medulla and its interstitial osmolality is decreased
Describe the distal convoluted tubule
- FIRST PART (macula densa): linked to the juxtaglomerular complex. It provides feedback control of the GFR and tubular fluid flow in the same nephron.
- SECOND PART: very convoluted.
Describe the connecting tubule.
- Connects the end of the DCT to the collecting duct
- Mainly in the outer cortex.
RECAP: describe the functions of the DCT.
- Solute reabsorption continues without H2O reabsorption. There is high Na+/ K+ - ATPase activity in the basolateral membrane.
- Further dilution to the tubular fluid. The ADH can exert its actions.
- Acid-base balance via the secretion of NH3.
Describe the formation of the collecting duct.
Joining of collecting tubules
Describe the structure of the collecting duct.
- Cuboidal epithelia
- Very few mitochondria
What are the two types of cell in the collecting duct?
intercalated cells
principal cells
What is the role of intercalated cells?
Acidification of urine and acid-base balance
What is the role of principal cells?
Sodium balance and ECF volume regulation
What is the purpose of the collecting duct?
Final site for processing urine
What is the collecting duct permeable to?
- Permeable to H2O (by ADH) and urea.
List some major factors contributing to the build-up of solute concentration in the renal medulla. PART 1
- Active transport of Na+ and the co-transport of K+ and Cl- out of the thick ascending limb into the medullary interstitium.
- Active transport of ions from the collecting ducts into the medullary interstitium.
List some major factors contributing to the build-up of solute concentration in the renal medulla. PART 2
- Facilitated diffusion of large amounts of urea from the collecting ducts into the medullary interstitium.
- Diffusion of water from the ascending limbs of tubules into the medullary interstitium.
What is Polycystic Kidney Disease (PKD)?
Genetic disorder characterised by the growth of numerous cysts in the kidney.
Describe a disease of the glomerulus.
Glomerulonephritis (GN).
- Inflammation of the glomeruli of some or all nephrons
- Primary or secondary to systemic diseases like diabetes mellitus.
There are also inherited diseases of the glomerular basement membrane.
Describe how diseases of the tubules could occur.
- Obstruction (reducing glomerular filtrations)
- Impairment of transport functions (reducing water and solute reabsorption), eg. Fanconi’s Syndrome.
Describe hypertension.
- Kidneys regulate ECF volume and hence influence blood pressure.
- Mechanisms in response to a high BP can leads to chronic kidney damage.
Describe congestive cardiac failure.
- Fall in cardiac output leads to renal hypoperfusion - hypovolemia
- Compensation results in pulmonary oedema.
Describe diabetic nephropathy.
Filtering system of the kidneys gets destroyed over time.
Describe lithium treatment.
Results in acquired nephrogenic diabetes insipidus, due to the reduction of AQP2 expression.
What happens to the collecting duct during water excess?
→ Reduced ADH secretion
→ water remains in the collecting duct
→ large urine volume - more dilute
What happens to the collecting duct during water deprivation?
→ ADH secretion
→ Aquaporins are inserted
→ small urine volume - less dilute
How are urea levels in the kidney monitored?
→ Blood urea nitrogen test
What do increasing urea levels in the kidney indicate and why?
→ pre-renal failure
→ reabsorption is enhanced
How is urea reabsorbed from the collecting duct?
→ Urea is absorbed into the surrrounding capillaries and into the interstitium of the medulla
→ contributes to the osmotic gradient around the loop of Henle
How does urea enter the glomerular filtrate?
→ It filters freely through the glomerulus and passes down the tubule
What is urea?
→ Waste products formed in the liver during metabolic breakdown of proteins
How does ADH/ vasopressin cause the collecting duct to be more permeable to water?
- ADH binds to its V2 receptors on the peritubular capillary wall
- Insertion of aquaporins into the luminal membrane near the collecting duct
- Water is removed from the urine
- Stimulates the synthesis of new aquaporins
What happens when an osmoreceptor detects changes in osmolality?
→triggers ADH secretion from the posterior pituitary
→ taken to the kidneys
→ make the collecting duct permeable to water
What is the most important variable in regulating ADH secretion?
Plasma osmolality
What is the most important effect of ADH?
→ conserve body water by reducing the loss of water in the urine
How can you make the DCT permeable to water?
Add ADH
What do loop diuretics do?
→ act causing 20% of filtered Na+ to be excreted
What cells is the nephron made from?
→ a single layer of epithelial cells resting on a basement membrane
What is the sodium-glucose transporter called in the kidney?
SGLT-2
What is the effect of SGLT-2 inhibitors?
→ don’t allow glucose to be carried across with sodium into the peritubular capillaries
What is an antiport transporter?
→ transported species move in opposite directions
What is a symport transporter?
→ transported species move in the same direction
What is co-transport?
→ Movement of one substance down its concentration gradient
→ allows the transport of another substance against its concentration gradient
What is passive transfer?
→ Passive movement down the concentration gradient
What is active transport?
→ Moving a molecule against its concentration gradient
→ requires energy
What is the pathway substances have to take to be reabsorbed?
→cross the luminal membrane
→ diffuse through the cytosol
→ across the basolateral membrane
→ into the blood
What is excretion?
→ how unwanted substances are cleared into the urine
What is secretion?
→ moving from the peritubular capillary plasma into the tubular lumen
What is reabsorption?
→moving from the tubular lumen into the peritubular capillary
→ returning wanted substances into the blood
What is the glomerular filtrate?
→ An ultrafiltrate of plasma
When does urine formation begin?
→ large amounts of fluid that is free of protein is filtered from the glomerular capillaries into the Bowman’s Capsule.
What is the composition of glomerular filtrate?
→Same composition as plasma except that there are no cells and very little protein
What happens in the renal tubule?
→ Filtered fluid is converted to urine