4 Flashcards
Explain the sodium balance in the ECF (expansion)
- ingestion of sodium can vary (low salt diet 0.5 g/d to 20 g/d)
- kidney Na+ excretory rates must vary over wide range depending on diet
- Match excretion to ingestion
- urinary water excretion can be varied physiologically by the kidney
- if sodium ion excretion is LESS than intake, then a pt. Is in positive balance; extra Na ions are retained in the body primarily in the ECF
- when Na ion content of the ECF increases, there is a corresponding increase in ECF volume since water from nephron is drawn out
- blood volume and arterial pressure increase and oedema may follow
Why can’t we just add/remove water to plasma to change its volume?
- because that would change the plasma osmolarity
- need to add isosmotic solution to increase volume
- or remove isosmotic solution to reduce volume without changing osmolarity
- how do we add/remove an isosmotic solution?
- need to make water want to move
- so need to actively add/remove Na so water passively follows
Explain the sodium balance in the ECF (contraction)
- if Na ion excretion is greater than ingestion, then a pt. Is in negative balance
- excess Na ions are lost from body so Na ion content of ECF decreases and water remains in nephron
- ECF volume decreases so does blood volume and arterial pressure
- AMOUNT is affected not CONCENTRATION
Explain reabsorption of Na in kidneys
- 2 membranes are involved
- luminal/apical membrane and basolateral membrane
- involves 3Na2K ATPase
- different segments of the tubule have different types of Na transporters and channels on the apical membrane
- can occurs in paracellular fashion: between the gaps of the cells
- can occur in transcellular fashion: through the cell
What Na channels are in each area of the nephron?
Proximal tubule -Na/H anti porter -Na/Glucose symporter -Na/AA co-transporter -Na/pi Loop of Henle -NaKCC symporter Early DT -NaCl symporter Late DT and CD -ENaC (Epithelial Na channels)
Describe the PCT in regards to Na reabsorption
- 2 segments
- Early PCT: S1
- Late PCT: S2 and S3
- both segments have active Na/K ATPase on basolateral membrane
- uptake into capillaries governed by oncotic forces and hydrostatic forces
- different nephron segments use different apical transporters or channels for transcellular Na reabsorption
Describe the function of PCT in S1
-has basolateral 3Na2K ATPase
-also NaHCO3 co-transporter (acids and bases)
Apical channels
-Na/H exchange
-co-transport with glucose
-co-transport with AA or carboxylic acids
-co-transport with phosphate (NaPi channel sensitive to increase in PTH)
-Aquaporin 1 allows water move from lumen into cell
-Urea and Cl are left behind and increase in S1 to increase for the loss of glucose
-increase in Cl concentration creates a conc. Gradient for Cl reabsorption in S2-3
-Actively removing Na ions from inside tubular cell
-lower Na concentration inside the cell
-as a result a concentration gradient is established from high in lumen
-allows for glucose to go into cell and then eventually into interstitum, then into capillary
-sometimes transport of glucose can be against conc. Gradient thus It is active
Explain the relationship between glucose filtration, reabsorption and excretion to the plasma glucose concentriation
- as much glucose cam be reabsorbed back into plasma until it hits the transport maximum (Tm)
- when we exceed transport maximum, glucose ends up being excreted
- occurs in diabetic patients
- see graph
Explain Na and HCO3 reabsorption in PCT S1
- NaHCO3 splits in lumen
- Na goes into Na/H anti porter
- H comes out of lumen to make H2CO3 with HCO3
- H2CO3 goes through carbonic anhydrase to make H2o and CO2 which go into tubular cell
- rejoin as H2CO3 and then split into H and HCO3
- HCO3 goes through anion exchanged into capillary by exchanging with Cl
- allows for an osmole effect to bring water in
What is amiloride?
- diuretic that inhibits ENaC in DCT
- BUT also blocks the Na+/H+ anti porter in PCT, abolishing about 80% of the action of AGII on the secretion of H ions in PCT
What is isosmotic reabsorption?
- graph that shows the levels of reabsorption for different molecules, compared to the distance from Bowman’s space
- amount of Cl increases in the filtrate as other ions are removed, preferentially leaving it behind
- osmolarity remains unchanged
- ordinate=tubular fluid to plasma concentration ratio (TF/P)
- TF/P= 1 for a substance that is the same concentration in the tubular fluid and plasma (anything freely filtered at the glomerulus would have a TF/P=1 at the glomerulus)
Describe the action of early PCT at S2/3
- contains a basolateral 3Na-2K ATPase
- apical Na+ reabsorbed in S2-3 via Na-H exchange and one or more Cl-anion antiporters
- apical membrane has Na/H exchanger
- has a paracellular Cl transport (done freely)
- Movement of Cl results in positive transepithelial charge which helps drive Na and Cl via paracellular route
- about 4mOsmol gradient favouring water uptake from lumen
- aquaporin 1
How does the late PCT (S2/3) function?
- as Cl increases, paracellular reabsorption occurs with no use of energy
- diffusion through tight junctions
- proportion of tubular Cl- as the major anion increases as HCO3 decreases
Explain the amino acid reuptake in the proximal tubules
-on apical membrane there are sodium-dependent AA transporters
-on basolateral membrane there are passive AA transporters
At least 7 different transporters
-Basic AA/cysteine
-Glutamic and aspartic acids
-neutral amino acids
-imino acids
-glycine
-cystine and cysteine
-beta and gamma amino acids
How is the peritubular capillary isosmotic?
- proximal tubule is highly water permeable
- bulk transport or obligatory water reabsorption
- reabsorption is isosmotic with plasma
- PCT reabsorbs 65% water, 100% glucose and AA and 67% Na
- driving force is osmotic gradient established by solute absorption (ex. Osmolarity in interstitial spaces increase)
- hydrostatic force in interstitum increases
- increase in oncotic force in peritubular capillary due to loss of 20% filtrate at glomerulus but cells and proteins left in blood
- so that things can be rapidly reabsorbed back into blood
- increase in plasma concentration in efferent arterial goes to peritubular capillaries = increased osmotic force to reabsorb fluid in PCT
Explain how effectors can change renal sodium excretion
-changes in osmotic pressure and hydrostatic pressure alter the proximal tubule Na reabsorption (and thus water)
-PCT Na reabsorption is stimulated by AG2 (RAAS) under conditions of low BP (inhibited by amiloride)
-principle cells of DCT and CD targets for the hormone aldosterone
-when renal artery BP INCREASES
-reduced Na/H anti porter and reduced Na-K ATPase activity in PCT
-causes reduction in sodium resorption in PCT (glomerular tubular balance)
-leads to reduction in water resorption in PCT
-results in increased sodium (natriuresis) and increased water (diuresis) excretion
ECF volume decreased and initial BP rise diminished
-natriuresis and diuresis occur together
Explain the movement of fluid in the loop of Henle
Descending: squamous epithelium so no transport of solutes, just water reabsorption, but no NaCl
Ascending: no aquaporin channels so impermeable to H2O, but reabsorbs NaCl
-thus ascending limb is known as the DILUTING SEGMET
-tubule fluid leaving loop is therefore hypo-osmotic (more dilute) compared to plasma
What occurs in the descending limb of the loop of Henle?
- cortex to papilla interstitial concentrations gradient allows paracellular reuptake of water from descending limb
- this concentrates the sodium and chloride ions in the lumen of the descending limb ready for active transport in the ascending
Explain passive Na reuptake by the thin ascending limb
- water reabsorption in descending limb creates a gradient for passive Na ion reabsorption in thin ascending limb
- epithelium in thin ascending limb permits passive reabsorption by paracellular route
What is ROMK?
- Renal Outer Medullary K Channel
- expressed on apical membrane
- very efficient and good to take K out of cell and into lumen
- helps NKC22 in the Na reuptake at the thick ascending limb
- helps ClC-KB (chloride) to transporting Cl from cell to capillary
What is furosemide?
- a loop diuretic
- can block NKCC2 on the apical membrane of the thick ascending limb
- prevents active transport of Na, K and 2 Cl
- can cause hypokalemia
Explain K reuptake and secretion in the thick ascending limb
- NKC22 only works because ROMK gives K to it
- see diagram
What is spironolactone?
- is a K sparing diuretic
- stops ROMK which will cause diuresis
- prevents transport of Na into cell
What occurs in the DCT?
- water permeability of early DCT is fairly low
- active Na+ reabsorption (up to 5-8%) results in further tubular dilution: stimulated by aldosterone (RAAS)
- late DCT and collecting duct
- water permeability is variable depending on ADH (low Bp stimulates ADH, which increases water reuptake by aquaporin channels)
- extra water comes through DCT because of ADH
