Structure and function of the renal tubule Flashcards
What happens in the renal tubule?
→ Filtered fluid is converted to urine
What is the composition of glomerular filtrate?
→Same composition as plasma except that there are no cells and very little protein
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 glomerular filtrate?
→ An ultrafiltrate of plasma
What is reabsorption?
→moving from the tubular lumen into the peritubular capillary
→ returning wanted substances into the blood
What is secretion?
→ moving from the peritubular capillary plasma into the tubular lumen
What is excretion?
→ how unwanted substances are cleared into the urine
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 active transport?
→ Moving a molecule against its concentration gradient
→ requires energy
What is passive transfer?
→ Passive movement down the concentration gradient
What is co-transport?
→ Movement of one substance down its concentration gradient
→ allows the transport of another substance against its concentration gradient
What is a symport transporter?
→ transported species move in the same direction
What is an antiport transporter?
→ transported species move in opposite directions
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 are the techniques used to investigate tubular functions in humans?
→ Clearance studies
What are the techniques used to investigate tubular functions in animals?
→ Micropuncture & isolated perfuse tubule
→ Electrophysiological analysis
How is micropuncturing done?
→ isolate the nephron
→ sample tubular fluid in different parts of the nephron
How is the electrical potential measured?
→ Micropipettes are inserted into the cell
→PD is measured across the whole cell epithelium
What is patch clamping for?
→The current flow through an individual ion channel is measured
How is patch clamping done?
→ A blunt tip pipette is pressed against the cell membrane
What cells is the nephron made from?
→ a single layer of epithelial cells resting on a basement membrane
What are the 7 parts of the nephron?
→ PCT →Thin Descending limb → Thin ascending limb → Thick ascending limb → DCT → Collecting duct → Medullary collecting duct
What are the two types of nephron?
→ Cortical nephron
→Juxta-medullary nephron
What do juxta medullary loops do?
→ they have a long loop of Henle
→ They are better at concentrating urine
What percentage of each type of nephron do humans have?
→ 85% cortical
→ 15% juxta medullary
What are the efferent arterioles in the juxtamedullary nephrons divided into?
→ Specialized capillaries (vasa recta)
→ they extend downward into the medulla and lie side by side with loops of Henle
Where is the PCT?
→ Adjacent to the Bowmans capsule
What are the adaptations of the PCT for transport?
→ Mitochondria for active transport
→ Brush border on the luminal side which gives a large surface area for rapid exchange
→Enzymatic proteins and carriers
→ the PCT has a high permeability
How much is filtered at the PCT?
→ 65-70% of the filtered load
What is Fanconi’s syndrome?
→ Proximal tubule reabsorptive mechanisms are defective so glucose, amino acids, Na+, K+ are all found in the urine
What are the 3 functional segments of the loop of Henle?
→ Thin descending
→ Thin ascending
→ Thick ascending
What is the structure of the thin ascending & descending loops?
→ Thin epithelial cells
→ No brush border
→ few mitochondria
→ low metabolic activity
What is the structure of the thick ascending loop?
→ Thick epithelial cells → Extensive intracellular folding → Few microvilli →Many mitochondria → High metabolic activity
What is the function of the loop of henle?
→ role in diluting and concentrating urine
→ adjusts the rate of water secretion/absorption
What are the permeabilities of the loop of henle?
→ Only the descending limb is permeable to water
→ the other two are impermeable to water
What do the loop diuretics do?
→ act causing 20% of filtered Na+ to be excreted
Describe how the countercurrent multiplier works
→on the ascending limb side there are a lot of Na+/K+ pumps
→ They pump Na+ out all the time
→ Salt accumulates in the interstitial space around the loop of Henle
→ It pulls water out of the descending limb via osmosis
→water cannot be reabsorbed by the ascending limb
→ as fluid flows down the osmolality increases
→ all the fluid is more concentrated
→as the fluid moves out it is hypo-osmotic
What maintains the medullary osmotic gradient?
→the vasa recta forms in a countercurrent to the loop of henle
→water can diffuse into the blood
→ Salts can diffuse into the loop of henle
What is the first part of the DCT and what is it linked to?
→ Macula densa
→ Juxtaglomerular complex
What does the macula densa do?
→ provides feedback control of the GFR
What are the functions of the DCT?
→ Solute reabsorption without H2O absorption
→ high Na+/K+ ATPase activity in the basolateral membrane
→ dilution of tubular fluid
→ Role in acid base balance via the secretion of NH3
How can you make the DCT permeable to water?
→ using ADH
What are the collecting ducts formed from?
→ joining collecting tubules
What are the 2 types of cells in the collecting ducts?
→ intercalated cells
→ principal cells
What kind of epithelium is in the collecting duct?
→ cuboidal epithelia
What is the collecting duct permeable to?
→ urea
→ made permeable to H2O by ADH
What do intercalated cells do?
→ Involved in acidification of urine and acid-base balance
What do principal cells do?
→ Play a role in Na balance and ECF volume regulation
Where is ADH made and stored?
→ In the hypothalamus
→ In the pituitary gland
How does ADH concentrate urine?
→ triggering the kidney tubules to reabsorb water back into bloodstream
What is the most important effect of ADH?
→ conserve body water by reducing the loss of water in the urine
What is the most important variable in regulating ADH secretion?
→ Plasma osmolality
What are changes in osmolality sensed by?
→ osmoreceptors
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
How does ADH/ vasopressin cause the collecting duct to be more permeable to water?
1) ADH binds to its V2 receptors on the peritubular capillary wall
2) it leads to the insertion of aquaporins into the luminal membrane near the collecting duct
3) water is removed from the urine
4) it stimulates the synthesis of new aquaporins
What is urea?
→ Waste products formed in the liver during metabolic breakdown of proteins
How does urea enter the glomerular filtrate?
→ It filters freely through the glomerulus and passes down the tubule
How is urea reabsorbed from the collecting duct?
→ as water is reabsorbed from the CD
→ Urea is concentrated so that it moves out
→ absorbed into the surrrounding capillaries and into the interstitium of the medulla
→ contributes to the osmotic gradient around the loop of Henle
What do increasing urea levels in the kidney indicate and why?
→ pre-renal failure
→ reabsorption is enhances
How are urea levels in the kidney monitored?
→ Blood urea nitrogen test
What happens to the collecting duct during water deprivation?
→ ADH acts
→ Aquaporins are inserted
→ small urine volume - less dilute
What happens to the collecting duct during water excess?
→ no ADH acts
→ water remains in the CD
→ large urine volume - more dilute
What kind of fluid enters the collecting duct?
→ Hypo-osmotic fluid
What are the 4 factors that allow the medullary osmotic gradient to be maintained?
→ Active transport of Na+ and co-transport of K+ and Cl- out of the thick ascending limb into the medullary interstitium
→ Active transport of ions from collecting duct into the interstitium
→ Facilitated diffusion of urea from collecting ducts into the medullary interstitium
→ Little diffusion of water from ascending limbs of tubules into medullary interstitium
What is polycystic kidney disease?
→ genetic disorder characterized by growth of numerous cysts in the kidney
What are diseases of the glomerulus called?
→ glomerulonephritis
What happens in diseases of the glomerulus?
→ inflammation of glomeruli or some or all of the nephrons
→ can be primary or secondary to things like diabetes
What are the two diseases of the tubules?
→ Obstruction
→Impairment of transport functions
How can hypertension lead to kidney damage?
→ Kidneys regulate ECF and influence BP
→ compensatory mechanisms in response to high BP leads to chronic kidney damage
How can congestive cardiac failure lead to kidney damage?
→ Fall in cardiac output
→ renal hypoperfusion
→ registered as hypovolaemia
→ compensation results in pulmonary oedema
How does diabetic nephropathy lead to kidneys being damaged?
→ Filtering system of the kidneys get destroyed over time
What does lithium treatment result in?
→acquired nephrogenic diabetes insipidus
→ reduced aquaporin 2 expression
