Renal Physiology - PCT/Loop of Henle/DCT/Collecting duct Flashcards
- PB_BK_12 Capillary dynamics and interstitial fluid; osmosis, filtration and convection - PB_BK_13 Osmolarity: osmolality, partition of fluids across membranes, tonicity - PB_BK_16 Active cellular transport mechanisms PB_BK_53 Regulation of water and electrolyte [Na+, K+, Ca++, Mg++, PO4--,] balance; response to fluid loss /hypovolaemia. Role of urea and creatinine measurement.
What is the formula for net filtration in the bowman’s capsule?
This is the balance between the hydrostatic pressure of the plasma vs the hydrostatic pressure in the bowman’s capsule, countered by the effect of plasma oncotic pressure.
Plasma hydrostatic pressure (Pc) 48mmHg (Due to the efferent arteriole)
Interstitial hydrostatic pressure (Pi) 10mmHg
Plasma oncotic pressure (πi) 25mmHg
Net filtration pressure (NFP)
NFP = Pc - Pi - πiNFP = 48 - 10 -25NFP = 15mmHg
Describe the glomerulus
A highly specialised network of fenestrated capillaries designed to facilitate rapid filtration of small molecules and fluid into the renal tubule.
Glomerular capillaries are 5,000x more permeable than the BBB, with pores 80nm wide.
Three layers contribute to flomerular filtration
Capillary endothelium
Bowman’s capsule endothelium (Formed from podocytes which prevent molecules larger than 70,000 Da from filtering through)
Basement membrane
How can filtered substances be reabsorbed in the proximal tubule?
Primary active transport
ATP is used to drive substrates across a membrane, against their concentration gradient
Sodium/Potassium pump
Active calcium reabsorption across the basal membrane
Hydrogen ion secretion
Hydrogen/Potassium exchange on the apical membrane
Seconary active transport
Uses ionic gradients established as a result of the above to drive a second substrate across the membrane, against its concentration gradient
Sodium is commonly the driving ion
Can either be co-transport or countertransport
Facilitated diffusion
Via ion channels and transporters down the ion’s concentration gradient
Glucose via GLUT transporters
Paracellular transfer
Substances can move between cells within the nephron (usually down a concentration or electrical gradient)
Solvent drag
Water is reabsorbed (most efficiently via aquaporins) and can drag solutes with it
What happens in the proximal convoluted tubule?
IMAGE of ratios
The vast majority of reabsorption of filtered solute and fluid occurs in the PCT
60-70% of sodium, calcium and chloride ions
5-60% of potassium ions
90% of bicarbonate ions
All glucose (Assuming Tmax as not been exceeded (plasma conc. <11mmol/L)
Majority of filtered amino acids
Proteins re-absorbed via pinocytosis
By the end of the PCT, the fluid has very little glucose, amino acids and bicarbonate compared with plasma, with slightly higher concentrations of Na/K/Cl than plasma, and a high concentration of insulin
How is sodium reabsorbed in the PCT?
https://teachmephysiology.com/wp-content/uploads/2017/03/PCT-reabsorption-1.jpg
WHY CHLORIDE REABSORPTION?
80% undergoes active countertransport using hydrogen ion secretion
This facilitates chloride and bicarbonate reabsorption
How is chloride/bicarbonate reabsorbed in the PCT?
How is glucose handled by the kidney?
Freely filtered by the glomerulus, proportionally to plasma concentration.
Usually completely reabsorbed in PCT, with distal segments of nephron only used if the proximal parts are overwhelmed
Step 1
Sodium-Glucose linked transport (STLT) co-transporters use the sodium concentration gradient to actively move glucose up its concentration gradient
Step 2
GLUT-facilitated diffusion across basolateral membrane into interstitial fluid
Sodium pumped into the interstitium by the NaKATPase pump to maintain the concentration gradient necessary for step 1.
This process has a maximum rate - Tmax (Tubular maximum) of 300-380mg/minute of glucose, seen at plasma concentration of 10-12mmol/L.
Draw a graph showing the relationship between renal excretion of glucose and plasma concentration.
IMAGE
X axis: [Glucose] plasma (mMol/L)
Y axis: Rate of glucose transfer (mg/min)
Filtration: Linear, directly proportional relationship between plasma glucose and filtration, starting at zero and at a steep angle matching that of the re-absorption line.
Reabsorption: Starts at 0, and sharply plateaus at 11mmol/ml, with a rate of 300mg/min (Tmax)
Excretion: starts at 11mmol, rising linearly in proportion to the filtration line.
Draw and explain the function of the loop of Henle
IMAGE Loop of Henle
Concentrates urine via a countercurrent multiplier, which creates a hypertonic interstitium to draw water out of the renal tubules and collecting ducts.
Functionally distinct thin descending limb, and an ascending limb (which is impermeable to water), initially thin but transitioning to thick.
The thin descending limb can only reabsorb water (driven by higher interstitial osmolality), concentrating tubular fluid as it descends into the loop.
The thick part of the ascending limb actively reabsorbs sodium, potassium and chloride (NKCC co-transporter) back into the interestitium as well as bicarbonate, excreting H+ ions into the tubule - increasing the osmolality of the surrounding interstitium further.
Because solutes are actively removed in the thick ascending limb, tubular fluid is diluted relative to fluid entering the loop - at around 1010mOsm/kg. Loop diuretics work by inhibiting the NKCC cotransporter
The vasa recta (which follow the loop down) contribute to this process by having relatively low flow, allowing concentrations of solutes to equilibrate at the top and bottom of the loop of henle, and preventing washing out of the solutes.
Only 15% of nephrons reach the deepest parts of the medulla
What happens in the distal convoluted tubule
Sodium, chloride and potassium reabsorption initially
Further along, K+ diffuses back into the tubule down its concentration gradient
No water is re-absorbed, further diluting the fluid
The DCT allows sodium and water reabsorption to be regulated and adjused via the macula densa and RASS system
Describe the different primary aquaporins found in the Kidney
4 Aquaporins of primary significance
1. Found in PCT and descending limb of loop of Henle, making them highly permeable to water
2. Under influence of ADH in the collecting ducts (apical membane)
3. Collecting ducts (basal membrane)
4. Collecting ducts (basolateral membrane)
13 aquaporins found in the body. Aquaporin 4 is most relavant in the CNS and regulation of CSF
How does the collecting duct work?
IMAGE
Variable permeability to water, under influence of ADH. Driven by the osmotic gradient generated by the adjacent loop of Henle. Aldosterone stimulates the reabsorption of Na⁺ in exchange for H⁺ and K⁺ ions.
