structure and function of the renal tubule Flashcards
reabsorption
when the direction of movement is from the tubular lumen into the peritubular capillary plasma
secretion
when the movement is in the opposite direction to reabsorption i.e. peritubular plasma into tubular lumen
for a substance to be reabsorbed from the tubule what must it first cross?
it must first cross the luminal membrane – diffuse through the cytosol – across the basolateral membrane and into the blood (transcellular transport). Vice versa for secretion
2 physiological processes involved in reabsorption
active and passive transfer
Active Transfer/Primary Active Transport:
Moving molecule/ion against conc gradient (low→high)
Operates against electrochemical gradient
Requires energy - driven by ATP
Passive Transfer:
Passive movement down concentration gradient (requires suitable route)
Active removal of one component - concentrates other components
Co-transport/Secondary Active Transport:
Movement of one substance down it’s concentration gradient - generates energy
Allows transport of another substance against it’s concentration gradient
Requires carrier protein
2 types: symport and anti-port
how do lipid substances, ions and natural substances move through the membrane?
lipid soluble substances move through lipid matrix
ions and neutral substances move through water filled protein channels
symport and antiport
Symport = transported species move in same direction e.g. Na+ - glucose
Antiport = transported species move in opposite directions e.g Na+ - H- antiport
If a substance is going down its concentration gradient passively, it can generate energy to take another substance either in the same direction (symport), or the other direction (antiport)
how does the co transport of sodium and glucose work?
because Na moves into the cell down it’s concentration gradient which creates lots of energy
this means it can pull other substances along with it - cotransport (a form of secondary active transport)
for Na to pull another substance with it needs a coupling mechanism – carrier protein
sodium glucose transport n tubule
high Na+ conc in tubular fluid, flows down its concentration gradient into cell
in this process it generates energy so it can take a molecule across its concentration gradient - glucose
Na+ and glucose move into the cell via the SGLUT-2 transporter
as glucose levels build up in the cell, it diffuses down its concentration gradient into blood via the GLUT-2 transporter
Na+ enters the blood via sodium potassium ATPase pump.
what other movement does the sodium potassium ATPase pump help with?
movement of other substances with sodium
amino acids reabsorbed (supporter)
also aids movement of H+ ions but an ANTIPORTER is used, so H+ ions are secreted into the tubular fluid and are excreted out in the urine makes the urine a bit acidic
a mutation in the gene that encodes for SGLUT 2 causes what?
get familial renal glycosuria – glucose in the urine
Patients don’t make SGLUT 2, so all the glucose that is filtered is just dumped into the urine and remains there
what are SGLUT 2 inhibitors are used to treat?
diabetes
name some techniques to investigate tubular function
- Clearance studies
- Micropuncture & Isolated Perfused Tubule
- Electrophysiological Analysis (look at notes)
- Potential measurement
- Patch clamping
Micropuncture
Direct sampling of tubular fluid in different parts of nephron
- puncture tubule
- inject viscous oil to block ends
- inject fluid for study
- sample and analyse
tubule can be divided into how many segments?
7
- PCT
- Thin Descending Limb, LoH
- Thin Ascending Limb, LoH
- Thick Ascending Limb, LoH
- Distal convoluted tubule (DCT)
- Collecting/Connecting tubule
- Medullary Collecting duct
throughout its length what is the nephron comprised of?
a single layer of epithelial cells resting on a basement membrane
2 Types of Nephron
Cortical nephron - 85%
Short LoH
Juxta-medullary nephron - 15%
Long LoH
they have different vascular systems
Juxta-medullary nephrons
long-reach loops that penetrate deep into the medulla - better at concentrating urine
long efferent arterioles extend from glomeruli to outer medulla and are divided into specialised capillaries called vasa recta - they extend downward into medulla and run in parallel with the LoH
the nephrons with the long LOH play a very crucial role in?
concentrating and diluting urine
Proximal Convoluted Tubule
directly adjacent to Bowman’s capsule
high capacity for reabsorption
special cellular characteristics:
- highly metabolic, numerous mitochondria for active transport
- extensive brush border on luminal side –> large SA area for rapid exchange
what are located in the luminal and basolateral membranes of the PCT
enzymatic and protein carriers, primary and secondary active transport systems, which together with its permeability characteristics make the PCT the major site of reabsorption of the glomerular filtrate
PCT - lysosomal enzymes
Glomerular filtrate is protein free but some small proteins (<60kD) get through
These proteins are taken up into the cell by endocytosis → degraded by lysosomal enzymes into amino acids and simple sugars, and reabsorbed into plasma
by the end of the early PCT whats been absorbed?
essentially all of the glucose and amino acids and much of the HCO3- have been reabsorbed
HCO3- is preferentially absorbed relative to what?
Cl-
where does Cl- concentration rise, and what is the effect of this?
the concentration of Cl- rises in the tubular fluid, establishing a Cl- concentration gradient from lumen to peritubular fluid
as Cl- moves passively down its concentration gradient the lumen acquires a positive electric charge relative to the peritubular fluid
Na+ moves passively along the gradient with Cl-
Fanconi’s Syndrome
all proximal tubule reabsorptive mechanisms are defective, so glucose, AA, Na+, K+ etc. are all found in the urine
how does the H2O reabsorption occur in the PCT?
Water is reabsorbed by osmosis – as the various substances are driven across they will pull water across
3 functionally distinct segments of the LoH:
Thin descending limb
Thin ascending limb
-thin epithelial cells, no brush border, few mitochondria & low metabolic activity
Thick ascending limb
-thick epithelial cells, extensive lateral intercellular folding, few microvilli, many mitochondria, high metabolic activity
the LoH has a critical role in what?
concentrating/diluting urine »adjusting rate of water secretion/absorption by creating an osmotic gradient in the medulla (tissue around the LoH)
so water is pulled out of the LoH by osmosis
what part of the LoH is permeable to water?
only the descending limb is permeable to water – the ascending limb (both thick and thin parts) is impermeable to water, but very active in reabsorbing sodium
what are loop diuretics and where do they act?
act at the thick ascending limb of the LoH to inhibit sodium, chloride and potassium reabsorption
they cause 20% of filtered Na to be excreted, by blocking Na-transport out of LoH
diuretics
allow you to pee out out increased amount of fluid for whatever reason