Renal Lectures 2 and 3 Flashcards
Which part of the tubule reabsorbs most of filtered fluids?
The proximal tubule reabsorbs 67% of filtered water and Na, K, Cl and other solutes. Key element of this is Na+ K+ ATPase.
How does ion concentration differ as the fluids travel the proximal tubule?
In 1st have of proximal tubule, Na is reabsorbed with HCO3- (H+).
In 2nd half of proximal tubule, Na is reabsorbed with Cl-.
Na in will be greater then Na out making a steep chemical gradient.
Paracellular route
Tight junctions -> passive diffusion
Transcellular route
Active transport through cell, includes transapical, transbasal, and translateral pathways
What drives the Na intro the cells and out of the lumen
Electrochemical gradient - cell interior negative. Na into cell is passive.
Is Na from cell to interstitial space passive or active
Active
Is Na backleak through tight junctions from cell to lumen passive or active
Passive
Describe sodium transport along the nephron
Early proximal tubule - sodium and bicarbonate absorbed
Late proximal tubule - sodium and chloride ions absorbed
Ascending limb - NaCl absorbed
Distal tubule - NaCl absorbed
Collecting duct - NaCl absorbed
How is sodium reabsorbed in early proximal tubule
Na/H exchanger and Na-solute cotransporter
How is sodium reabsorbed in late proximal tubule
Apical sodium transporters: parallel exchangers and Na/H and Cl/base
How is sodium reabsorbed in thick ascending limb
Apical sodium transporter - Na/K/2Cl triporter
How does proximal fluid composition change along proximal tubule
- Chlorine rises and plateaus
- Na stays consistent
- Pi drops and plateaus
- HCO3-, Glucose, and Lactate drop even further - depletion of major solute
How is sodium reabsorbed in the early distal tubule
Apical sodium transporter - NaCl cotransporter
This is anti-natuiretic - decreases sodium excretion by anti natuiretic agents
How is sodium reabsorbed in the late distal tubule and collecting duct
Apical sodium transporter - Epithelial sodium channel.
Na absortion to principal cell.
How do angiotensin and NE affect sodium reabsorption
Increases absorbtive capacity
Stimulate Na/H transporter
Innervated with sympathetic activity
Describe the apical effect of Na entry by NE and AII
NE -> a2 receptor -> Gai
AII -> AT1 receptor -> Gai
Results in decrease cAMP concentration, decrease PKC activity, stimulates Na/H exchanger
Describe the basolateral effect of Na extrusion by NE
NE-> a1 receptor -> Gaq
Activates PLC to increase intarcellular Ca2+ concentration and stimulate Na/K ATPase
Aldosterone
Modulates sodium transport in principal cells by increasing sodium absorption. It binds to the mineralcorticoid receptor and migrates to nucleus to produce protein which can be used to make channels and also stimulates mitochrondria to make ATP. It is an anti-naturietic agent - increases absorption.
Atrial Natriuretic Peptide (ANP)
Targets principal cell to block Na uptake -> urine volume increases.
Increases CGMPby binding to its receptor. Increased CGMP inactivates epithelial sodium channel by
1. binding to an allosteric modifer site on the channel
2. phosphorylating the channel via cGMP-dependent PK.
Diuretics
Increase in sodium excretion by target specific transport system
Decreased absorption, increeased urine
Which sections of the nephron are water impermeable
Thick ascending limb, early distal tubule, collecting duct
Where is very dilute urine found in nephron
After TAL and around early distal tubule, Na gone but water not yet reabsorbed
How does ADH affect water transport along the nephron
More dilute in late distal tubule and medulary collecting duct because ADH makes cells more water permeable.
Mode of action of ADH
ADH, aka vasopressin, creates water channels.
Describe distribution and balance of potassium
Most K+ is reabsorbed and in intracellular compartment (90%). Small percentage in feces and urine.
These stimulate K+ exchange into the ICF while Na goes out (ATPase pump)
Epinephrine released from adrenal gland and insulin from pancreas; both released due to increased extracellular K+.
Describe reabsorption of K+ in the nephron for a diet low in potassium
80% reabsorbed in proximal convuluted tubule
10% reabsorbed in thick ascending limb
Only 2% of filtered load remaining in collecting duct
Describe reabsorption of K+ in the nephron with a healthy amount of K+ in diet
80% reabsorbed in proximal convuluted tubule
10% reabsorbed in thick ascending limb
20-180% secreted by initial collecting tubule
10-150% of filtered load remaining in collecting duct
K+ transport in proximal tubule
K+ channel (K out)
K+/Cl- symporter (K out)
Na/K exchanger (K in)
K+ transport in thick ascending limb (TAL)
Na/K Cl symporter (K in)
K channel (K out)
Na/K antiporter (L in)
K+ transport in Cortical collecting tubule (CCT): alpha-intercalated cell
Na/K antiporter (K in)
K/H antiporter (K in - therefore increased pH / more basic extracellularly)
K channel (out)
K+ transport in cortical collecting tubule: principal cell
Passive K channel out
Active K/Na pump exchanger K in
Increased plasma K+ concentration
Increasing K+ secretion, to a plateau
Tubular flow rate to K+ secretion
Higher tubular flow rate = higher K+ secretion rate
A diet (high/low) in K+ has a higher secretion rate per same tubular flow rate
High
How is K+ regulated by pH
Increase in pH (more basic) = steeper increase in K+ secretion.
How is K+ regulated by aldosterone
Increase in aldosterone = increase in secretion of K+
