Structure and function of the renal tubule Flashcards
What is the difference between the glomerular filtrate and plasma composition?
No cells and very little protein in glomerular filtrate
Why is the composition of the plasma not the same as the urine?
Selective modification of filtrate as it passes through tubule
What is reabsorption equal to?
Reabsorption = tubular lumen → peritubular plasma
What is secretion equal to?
Secretion = peritubular plasma → tubular lumen
Where do substances move through to be reabsorbed/ secreted?
Through epithelial cell of the tubular lumen
Thriugh peritubular fluid
Through peritubular capillary
Vice versa for secretion into the tubular lumen
What 2 physiological processes are involved with secretion and reabsorption?
Active and passive transfer
Describe the premise of Active Transfer/Primary Active Transport
- Moving molecule/ion against conc gradient (low→high)
- Operates against an electrochemical gradient
- Requires energy - driven by ATP
Describe the premise of Passive Transfer
- Passive movement down a concentration gradient (requires suitable route)
- Active removal of one component concentrates other components
Describe the premise of 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 anti-port
What is symport and antiport transfer?
Symport = transported species move in the same direction e.g. Na+-glucose
Antiport = transported species move in opposite directions e.g Na+-H- antiport
Describe the combination of active and passive mechanisms for transcellular transport over luminal and basolateral membranes
- There is a high concentration os Na+ in tubule lumen (140mM) - this moves into the epithelial cells down a concentration gradient, aided by the electrochemical gradient.
- This generates energy so glucose can be transported against its concentration gradient into the epithelial cell, using a symport protein (SGLT2)
- Glucose is the transported down its concentration gradient from the epithelial cell into the PT capillary by a GLUT-2 transporter
- Sodium in the epithelial cell is actively pumped by a Na+/K+ pump int PT capillary - keeps Na+ low in epithelial cell
This is the transcellular mode of transport
Familial Renal Glycosuria is caused when you cannot produce SGLT2
SO SGLT2 inhibitors to treat diabetes – - Dapagliflozin (Europe) & Canagliflozin (USA)
- A symport also transports sodium and AA into epithelium via a symport protein, and an antiport transports sodium into epithelial cell and hydrogen ions out into tubule
- These sodium are actively transported into the capillary by a Na+/ K+ ATPase
What techniques investigate tubular function?
- Clearance studies
- Micropuncture & Isolated Perfused Tubule
- Electrophysiological Analysis
- Potential measurement
- Patch clamping
1 = applied to man
2 & 3 = applied to lab animals
What happens during a micropuncture? (how is it performed?)
- Puncture
- Inject viscous oil
- Inject fluid for study
- Sample and analyse
What happens during an electric potential measurement ( potential measurement)? (how is it performed?)
- Combine with microperfusion to alter potential difference (PD)
- Measure whether ion moving with or against an electrochemical gradient
- Actively transported?
What happens during patch clamping (how is it performed)?
- Current flow through individual ion channel measured
- Measure electrical resistance
- Across patch of cell membrane
- Changes when channels open/close - Types of channels & response to drugs & hormones
Describe the structure of the nephron (done previously)
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What are the 2 types of nephrons and how are they different?
The major anatomic difference between the Cortical nephrons & Juxtamedullary nephrons is the length of the loops of Henle.
Cortical neprhons have short-reach loops that just penetrate the boundary between the inner and outer zones of the medulla. These loops do not extend into the medulla.
Juxtamedullary nephrons have long-reach loops that penetrate deep into the medulla. (better at concentrating urine) In humans about 15 per cent of nephrons are juxtamedullary and 85 per cent are cortical.
Vascular system is also different.
Cortical nephrons – entire tubular system is surrounded by and extensive network of capillaries
Juxtamedullary nephrons – long efferent arterioles extend from glomeruli to outer medulla and divided into specialised capillaries (vasa recta) that extend downward into medulla and lie side by side with loops of Henle
The kangaroo rat is a rodent, but it is unlike any other rodent on Earth: it is able to survive in the desert with virtually no drinking water. But how is it possible to live with virtually no drinking water? The answer lies mainly in the rat’s kidneys. Research has shown that the kangaroo rat produces the most concentrated urine of all mammals, and only passes a few drops per day. The kangaroo rat’s Loop of Henle is much longer than that of other rodents.
How does the PCT have a high capacity for reabsorption and special cellular characteristics?
Highly metabolic, numerous mitochondria for active transport
Extensive brush border on luminal side large surface area for rapid exchange
What is the function of the PCT?
Major site of reabsorption
~65-70% of filtered load reabsorbed here
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`What are the 3 segments of the loop of henle?
Thin Descending
Thin Ascending
- thin epithelial cells, no brush border, few mitochondria & low metabolic activity
Thick Ascending
- thick epithelial cells, extensive lateral intercellular folding, few microvilli, many mitochondria high metabolic activity
What is the role of the Loop of Henle?
Which part of the loop of henle is permeable to water and impermeable
LoH critical role in concentrating/diluting urine
»adjusting rate of water secretion/absorption
Descending thin LoH = permeable
Ascending LoH = impermeable
Describe the medullary osmotic gradient?
LoH creates an osmolality gradient in medullary intersitium
Collecting Duct traverses medulla: urine concentrated as water moves out by osmosis
Describe multiplication by LoH
Why is it called a countercurrent system?
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The descending and ascending loop of Henle is parallel and is therefore called a countercurrent system - flow in opposite direction
When fluid enters the loop is has the same osmolarity as plasma
On ascending limb there is lots of sodium-potassium transporters - pumping NaCl out - this enters the tissue space around LoH - this creates an osmotic gradient
This gradient pulls fluid out of the descending limb by osmosis - as it flows down the descending limb osmolarity increases as water is removed
In the ascending limb, salts are being pumped out so osmolarity decreases - hypo-osmotic
Describe the absorption and excretion of ions in the thick ascending LoH
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