Urinary7 - Control of Plasma Volume

Question 1

2 features of sodium balance

Answer 1

1. ) Ingestion - can widely vary from diet (0.5-20g per day)
   - kidney Na+ excretion rates varies depending on diet
2. ) Plasma Volume - sodium conc is manipulated to control plasma volume (water follows sodium)
   - cannot simply add or remove water because that will change plasma osmolarity

Question 2

2 forms of reabsorption and secretion

Answer 2

1. ) Transcellular - through the epithelial cells lining the lumen of the nephron
   - lumen –> cell –> interstitium –> capillary
2. ) Paracellular - in between the epithelial cells
   - goes straight from the lumen into the interstitium
   - lumen –> interstitium –> capillary

Question 3

5 general features of reabsorption

Sodium Pump
Aquaporins
Hydrostatic Pressure
Oncotic Pressure
Transport Maximum

Answer 3

1. ) Sodium Pump - 3Na-2K ATPase (moves Na out)
   - found on basolateral surface of the epithelial cells
   - drives many other transporters and channels
2. ) Aquaporins - channels allowing water reabsorption
   - found on apical and basolateral membrane
   - not found in ascending limb and DCT because they do not reabsorb water
3. ) Hydrostatic Pressure - primary driving force in the interstitum
   - water enters the capillaries due to higher HP
4. ) Oncotic Pressure - primary driving force in the peritubular capillaries
   - solutes enter the capillaries because of the greater oncotic pressure due to plasma proteins
5. ) Transport Maximum - max amount of a substance than can reabsorbed due to no. of transporters
   - once this is reached, the remaining substance stays in the nephron and excreted in urine
   - explains glycosuria in diabetics

Question 4

4 features of isosmotic reabsorption

Osmolarity
Ordinate
Decreasing TF:P Ratio
Increasing TF:P Ratio

Answer 4

1. ) Osmolarity - stays the same through the PCT
   - achieved by balancing out the ions
2. ) Ordinate - ordinate means the tubular fluid to plasma conc ratio is 1. TF/P ratio = 1
   - anything free filtered at the glomerulus has a ratio of 1
3. ) Decreasing TF:P - substances that are preferentially reabsorbed decrease in TF:P as you move further away from the Bowman’s space
   - these are glucose, AAs, lactate, HCO3-, phosphate
4. ) Increasing TF:P - chlorine reabsorption lags behind so you have more chloride in the tubules than plasma
   - this helps balance out the osmolarity to achieve isosmotic reabsorption

Question 5

5 features of reabsorption in the S1 segments of the proximal convoluted tubule (PCT)

Simple Transcellular Reabsorption (5 molecules)
2 Paracellular Reabsorption (2 molecules)
Complex Transcellular Reabsorption (1 molecule)
Molecules Left Behind (2 molecules)

Answer 5

1. ) Simple Transcellular Reabsorption - co-transport
   - Na-K ATPase moves Na+ into the capillary/interstitium, creating a Na+ conc gradient
   - molecules enters the cell via a Na-Molecule symporter
   - molecules then enters the interstitium via faciliated diffusion through specific channels. This occurs with:
   - GLUCOSE (100%), AAs (100%), UREA (50%),
   - PHOSPHATE, HYDROGEN IONS
2. ) Paracellular Reabsorption of Water - 65%
   - solutes leaving the lumen creates a conc gradient for water to simply enter the interstitium via osmosis
   - however, small amounts of water can also take the transcellular route using aquaporins
3. ) Paracellular Reabsorption of Potassium - 67%
   - 3Na-2K ATPase generates an osmotic and electrochemical gradient
   - water is reabsorbed following the osmotic gradient
   - K+ is reaborbed following the electrochemical gradient
4. ) Complex Transcellular Reabsorption of HCO3 - (80%)
   - very long process so has its own flashcard
5. ) Molecules Left Behind - urea and chloride increase in conc to compensate for loss of glucose
   - increasing Cl- creates a conc gradient for chloride reabsorption in S2 and S3

Question 6

4 steps in sodium bicarbonate (NaHCO3) reabsorption in the S1 segment of the PCT

Answer 6

1. ) NaHCO3 Dissociation - splits into Na+ and HCO3-
   - occurs because there is no transporter for sodium bicarbonate
2. ) Carbonic Acid (H2CO3) - HCO3- joins with H+
   - H+ ions come from the NHE on apical membrane which exchanges Na ions in the lumen for H+ in the cell
   - amiloride is a diuretic that can block the NHE which abolishes 80% of the action of ang II of secreting H+ ions in the PCT
3. ) Carbonic Anhydrase - H2CO3 –> H2O + CO2
   - carbon dioxide and water diffuses into the cells
   - some H2O enters the interstitium via paracellular diffusion through aquaporins. Aids water reabsorption
4. ) Reconversion - H2O + CO2 –> H2CO3 using carbonic anhydrase again in the cell
   - H2CO3 –> H+ and HCO3-, H+ re-enter lumen via NHE
   - HCO3- is transported into capillary/ECF using the anion exchanger (exchanges HCO3- for Cl- ions)
   - HCO3- also leaves the cell via the HCO3-Na symporter

Question 7

2 types of reabsorption in the S2-S3 segments of the PCT

4 steps in the active reabsorption of … ions

Answer 7

1. ) Paracellular Chloride Reabsorption - passive process
   - chloride goes down the transepithelial gradient
   - some Na+ also follow the Cl- leading to water (using aquaporins) to follow the Na+ ions
   - PCT reabsorbs 67% of all sodium

2.) Transcellular Chloride Reabsorption - active process

1. ) Na-K ATPase creates conc gradient for NHE to exchange Na+ for H+ ions
2. ) H+ ions in the lumen binds to an anion and they enter the cell where they then dissociate.
   - the H+ is then used again by the NHE
3. ) Anion now in the cell is exchanged for Cl- ions in the lumen by a chloride-anion exchanger found on the apical membrane
4. ) Cl- then enters the capillary via the K-Cl symporter

Question 8

4 effectors that can cause a change in renal sodium excretion

Answer 8

1. ) Increase in BP - causes reduced expression of NHE and reduced Na-K ATPase activity in PCT which leads to
   - reduced Na and water reabsorption –> decrease in BP
   - called pressure natriuresis and pressure diuresis

2.) Pressure Changes - changes in osmotic and HP alters Na/water reabsorption in PCT

3. ) Angiotensin II - stimulates PCT Na/water reabsorption during low BP
   - it is inhibited by amiloride

4.) Aldosterone - targets principle cells of DCT and CD

Question 9

5 features of reabsorption in the of loop of Henle

6 Substances Reabsorbed
Type of Filtrate

Answer 9

1. ) Water Reabsorption in Descending Limb - extremely permeable to water due to lots of aquaporin channels
   - large concentration gradient from the cortex to the papilla allows for easy paracellular reabsorption of water
   - epithelium is simple squamous w/ loose gap junctions
2. ) Passive Na+ Reabsorption in Thin Ascending Limb
   - water reuptake in DL creates high conc of Na in lumen
   - this creates a high conc gradient for passive Na+ reabsorption in the thin ascending limb
3. ) Active Na+ Reabsorption in Thick Ascending Limb
   - separate flashcard
4. ) Other Ion Reabsorption in the Thick Ascending Limb
   - K-Cl symporter and Cl- transporter on the basolateral membrane allows for reabsorption of K+ and Cl- ions
   - Mg2+ and Ca2+ undergo paracellular reabsorption

5.) Hypo-osmotic Filtrate - tubule fluid leaving the loop is more dilute (less solutes) compared to plasma

Question 10

3 transporters involved in the active reabsorption of Na+ ions in the thick ascending limb

2 types of diuretics (and examples) than can interact with these transporters

Answer 10

1.) Na-K ATPase - generates conc gradient for Na+ ions

2. ) NKCC2 - found on the apical membrane
   - transports Na+, K+ and 2Cl- from the lumen –> cell
3. ) ROMK (renal outer medullary K+ channel) - found on the apical membrane
   - transports K+ ions into the lumen to keep NKCC2 working and prevent hyperkalemia
4. ) Loop Diuretics - e.g. furosemide
   - blocks NKCC2 to prevent Na/water reabsorption
   - loop diuretics doesn’t inhibit ROMK –> hypokalemia
5. ) Potassium Sparing Diuretics - e.g. spironolactone
   - blocks ROMK, preventing Na+ reabsorption by inhibiting activity of NKCC2 due to lack of K+ ions

Question 11

2 types of reabsorption in the distal convoluted tubule (DCT)

Answer 11

1. ) Selective Na+ Reabsorption - stimulated by aldosterone (RAAS) therefore it only reabsorbs Na+/water during low plasma volume
   - water comes from the collecting duct since the permeability of the DCT to water is low (no aquaporins)
   - it can reabsorb 5-8% of Na+ ions
2. ) Calcium Reabsorption - enters the cell via Ca2+ channels then immediately binds to calbindin (transport)
   - it is then transported out by NCX (Na-Ca exchanger)
   - tightly regulated by parathyroid hormone and calcitriol (active vitamin D)

Question 12

5 features/differences between the early DCT and late DCT

2 transporters
2 diuretics
Regulation

Answer 12

1. ) Early DCT uses the Na-Cl symporter (NCCT) on the apical membrane
2. ) Late DCT uses NCCT and the epithelial sodium channel (ENaC) on the apical membrane
3. ) Movement through ENaC is not electroneutral so it drives paracellular Cl- ion reabsorption
4. ) ENaC is upregulated by aldosterone (RAAS)
5. ) Diuretics - weaker than loop diuretics because there is less water re-uptake in DCT than the ascending limb
   - NCCT can be inhibited by thiazides diuretics
   - ENaC can be inhibited by amiloride diuretics

Question 13

3 features of reabsorption in the collecting duct

Divisions
Principal Cells
Intercalated Cells

Answer 13

1. ) Divisions - split into the cortical (CCD) and medullary (MCD) regions and 2 distinct cell types also found:
   - principal cells and intercalated cells found in CCD
2. ) Principal Cells - reabsorption of Na+ ions via ENaC
   - uses exactly the same concept as the late DCT
   - ROMK is also found on the apical membrane which causes K+ secretion/excretion
   - water is also reabsorbed depending on ADH activity on aquaporins
3. ) Intercalated Cells - can be type A or B
   - Type A secrete H+ ions into the lumen from the cell using the H-K ATPase (exchanger) on apical membrane
   - Type B secrete HCO3- into the lumen using anion exchanger (HCO3-Cl) on the apical membrane