Lecture 10: Sodium Balance and Renal Sodium Transport Flashcards
What is the recommended dietary Na intake per day?
2.3 g per day of just Na or 7.02 g of NaCl
What happens if you decrease sodium retention from 99.6% (which is normal) to 95% (which is abnormal)?
You lose 1,275 mmoles of Na since there is 25,500 mmoles of Na in ECF
And since Na is the primary determinant of ECF, that means you lose 8L of fluid from the ECF alone!
Losing 8L (140 mEq per L) would lead to hypervolemia!!
How much Na is filtered?
25,500 mmole
How much Na is reabsorbed?
25400 mmole or 99.6% of sodium
So urine output should only be 100 mmole a day of sodium
How is the Na handled in the nephron segmentally?
- Freely filtered at glomerulus 25,5000 mmole a day
- 67% reabsorbed at proximal tubule
- not finely regulated at this point for Na
- 25% reabsorbed at medullary thick ascending limb (mTAL)
- 5% reabsorbed at level of DCT and connecting tubule
- 3% reabsorbed at collecting duct
- urinary secretion = ~100 mmole/day = 0.4% of filtered load
In the first 3rd of the proximal tubule, sodium is preferentially absorbed in what compound?
Sodium and Glucose (because glucose is absorbed fastest in the first 1/3 of proximal tubule
Could also be sodium, glucose and amino acids (since it drops really fast in the graph below but Berns didn’t include that as an answer choice)
What is back leak at level of proximal tubule?
Paracellulary Na movement from blood TOWARDS lumen due to negative lumen voltage (after all the + charges have been reabsorbed
How is sodium reabsorbed at the proximal tubule?
- Na-glucose transporter
- Na-H+ antiport
- Na-aminoacids cotransport
- Paracellularly with water
What are the basolateral membranes that make sure Na goes into the blood?
- Na/K atpase
- sodium channel (orange guy at the top right)
- HCO3—Na+ channel on BLM
What are the characteristics of the fluid reaching the later proximal tubule (after the first 1/3)?
It is high in Cl and low in HCO3-
What are the characteristics of proximal tubule Cl- reabsorption?
- paracellularly in proximal PT (goes along with sodium due to gradient)
- Transcellularly in late PT (through CFEX channel in late PT)
CFEX = Chloride formate exchange
What are the transporters that send Cl- from PT cell to blood?
- Cl-K symporter
2. Cl channel
What are the characteristics of Na and Cl- transport in thin limbs of LoH?
Thin descending limb has low NaCl permeability so NaCl concentration increases as fluid goes farther down the descending limb
Medullary interstitium has high NaCl concentration
Thin ASCENDING limb is permeable to Na+ so NaCl is passively reabsorbed from thin ascending limb
-fluid becomes more hypotonic as it reaches the thick ascending limb
What are the characteristics of sodium and chloride reabsorption in thick ascending limb?
Water impermeable
NKCC channels will absorb both Na and Cl (2Cl- for every Na)
This is where sodium dilution begins to occur
What is the diluting segment?
Thick ascending limb (because water is impermeable and sodium is absorbed)
What is Bartter’s syndrome?
Mutations in NKCC, basolateral Cl- or apical K+ channels
Associated with urinary sodium wasting
What are the characteristics of Na/Cl reabsorption at distal convoluted tubule (DCT1 and DCT2)?
Water impermeable
Na-Cl symporter is the main channel
What is Gitelman’s syndrome?
Syndrome in which Na-Cl symorter at DCT is impaired
Gives you same symptoms as thiazide
What are the key characteristics of sodium reabsorption in the principal cells of the cortical collecting duct?
Primary channel = ENaC
ROMK is also involved … potassium channel that pumps K+ out of cell when ENac pumps Na into the cell
Aldosterone upregulates ENac while amiloride antagonizes it
Water variability here varies with vasopressin levels
Sodium is NOT reabsorbed at the intercalating cells of collecting duct
What are the key characteristics of chloride absorption in the principal and intercalated cells of collecting duct?
- Cl- is primarily reabsorbed through paracellular pathway driven by large lumen negative voltage at level of principal cells
- Cl- is also absorbed via Cl-HCO3- antiport in the B(eta)-intercalated cells
* *remember there are both alpha and beta intercalated cells)
What happens to weight in comparison to sodium intake?
At steady state, a diet with stable sodium content means no change in one’s weight
If you gain 1 kg of weight, how much Na was gained as well?
140 mEq in order for new 1 kg of solution to be isotonic with rest of body (which usually has 140mEq of sodium per liter upon lab measurement)
Thus 1 kg of weight = 1 L = 140 mEq of Na
Which one of the following is primarily responsible for regulating sodium reabsorption in the collecting ducts?
Aldosterone
When effective circulating volume decreases, what senses it?
- renal baroreceptor = decreased GFR
-leads to renin release - atrial, pulmonary and CNS low-pressure receptor and carotid sinus and aortic arch
-stimulates ADH release and sympathetic activation of ANS - cardiac atria
-stretch stimulates ANP release
Thus, angio II, aldosterone, adrenergic neurotransmitters, ADH and ANP all lead to decreased sodium excretion
How is sodium reabsorption at proximal tubule regulated?
- Glomerulotubular balance
- Antinatriuretic factors
i. angio II
ii. sympathetic nervous system - Natriuretic factors (promotes natriuresis)
i. dopamine
ii. ANP
What are the primary effects of angio II and SNS on sodium reabsorption?
Stimulates Na-H exchanger as well as Na/K ATPase at basolateral membrane
What can the proximal tubule cells synthesize?
- Dopamine!! (which promotes natriuresis)
2. Angio II
What is the glomerulotubular balance?
Describes the phenomenon when changes in GFR are balanced by equivalent changes in tubular absorption
Constant fraction of filtered fluid and NaCl is reabsorbed
Mediated by luminal and peritubular factors rather than any specific hormonal influences
Glomerulotbular balance = regulation of sodium absorption at level of PT!!
What are the mediators of glomerulotubular balance?
Increased GFR = increased solute reabsorption = increase in oncotic pressure (20 to 40) for post-glomerular peritubular capillaries (the ones that comprise the vasa recta and such) = more reabsorption of fluid from tubule lumen into peritubular capillaries (since capillaries have higher oncotic pressure now
What does an increase in filtration fraction do in terms of the glomerulotubular balance?
- increases oncotic pressure of peritubular capillaries
- Increases hydrostatic pressure inside the tubule lumen (since you have higher GFR_
- decreases hydrostatic pressure in peritubular capillaries
These changes all favor reabsorption of tubular fluid into proximal tubule
How do you regulate sodium reabsorption at level of thick ascending limb?
- vasopressin stimulates NKCC2
- extracellular calcium activates basolateral membrane calcium sensing receptor (CaSR) which leads to inhibition of NKCC, apical K channel and Na/K ATPase
- activation of CaSR will promote sodium, potassium, calcium and magnesium wasting
How does hypercalcemia lead to sodium wasting and potassium wasting and calcium wasting and magnesium wasting?
Because it activates the basolateral calcium sensing receptor (CaSR) which leads to inhibition to NKCC, apical K channel and Na/K ATPase
Too much calcium = excessive Na and K secretion
How do you regulate sodium reabsorption at level of cortical collecting duct?
- aldosterone
- vasopressin and Angio II stimulate epithelial sodium channel (ENaC)
- Prostaglandins reduce ENaC activity and antagonize effects of AVP
What antagonizes activity of AVP and ENaC at level of collecting duct?
Prostaglandins
Thus how can NSAIDs affect renal function?
NSAIDs decrease prostaglandin synthesis
Thereby removing inhibitory effect against AVP and ENaC
Thus NSAIDs leads to greater Na reabsorption and greater H2O reabsorption
What is the MoA of aldosterone?
Aldosterone binds to mineralocorticoid receptor in cytoplasm
Ald+MR upregulates
i. ENaC
ii. N/K ATPase channels
Aldosterone also increases conductance of ENaC and N/K ATPase channels
Therefore greater aldosterone = greater number of open ENaC channels
Which of the following are most likely to be seen in a patient who has ECF volume depletion?
Reduction in urine sodium concentration
Reduction in blood pressure
What is the definition of hypovolemia?
Decreased total body sodium and water with decreased effective circulating blood volume
Hypovolemia is NOT dehydration
Hypovolemia = decreased effective arterial blood volume or decreased Na content
What are the causes of hypovolemia?
- Renal
i. diuretics
ii. osmotic diuretic (hyperglycemia)
iii. Hypoaldosteroneism
iv. salt-wasting nephropathies (and NSAID use?) - Extrarenal
i. Vomiting, diarrhea
ii. through skin (sweating or blood loss)
iii. Lungs
iv. Third space accumulations like ascites, edema or pancreatitis
When can total body sodium be misleading?
In the case of ascites and edema
Na is there but it is not where it needs to be because of the ascites
What is not informative in assessing volume status?
Serum sodium concentration
What is informative in assessing volume status?
Urine sodium concentration
What are the clinical findings of hypovolemia?
- orthostatic tachycardia
- hypotension and reduced cardiac output
- decreased tissue turgor
- Organ hypoperfusion and shock
What is the treatment for hypovolemia?
- NaCl and volume
- salt rich foods and water
- IV NaCl
- blood replacement
- Address underlying cause like stopping diuretics and treating hyperglycemia
What is prerenal azotemia?
Refers to reduced GFR due to impaired renal perfusion (prerenal)
Also refers to elevation of nitrogenous products in the blood (azotemia)
Refers to laboratory findings of higher BUN and creatinine but BUN increases at greater rate than creatinine increase
Why does BUN levels increase more than creatinine levels?
Because urea gets reabsorbed whereas creatinine only gets secreted…in this cause urea is being reabsorbed as well so increases by greater amount
What does postrenal azotemia mean?
Means you get a build up of nitrogenous products due to obstruction of the urinary tract
What is the definition of hypervolemia?
Increased total body sodium and water
May be increased or decreased “effective” circulating blood volume
What are the causes of hypervolemia?
Renal
i. acute kidney injury and chronic renal disease can increased effective arterial blood volume (EABV)
ii. nephrotic syndrome (can be decreased or increased EABV)
Extrarenal
i. Heart failure decreases EABV
ii. Hepatic cirrhosis with ascites decreases EABV
What is the appropriate treatment for a patient with chronic kidney disease, HTN and edema?
NaCl restriction
Diuretics
Do not give bed rest, IV albumin infusions and water restriction
-water restriction won’t do shit since Na is primary determinant of EABV
What are the clinical findings of hypervolemia?
- Peripheral edema
- Ascites
- Pulmonary edema
- Increased JVP
- BP variable
What are the treatments for hypervolemia?
Depends on cause
- restrict NaCl intake
- diuretics
- dialysis
- heart failure management; heart transplant
- liver transplant
In an individual ingesting 2300 mg sodium per day who is at steady state with stable weight, daily urine sodium excretion will be close to what?
2300 mg/d
Urine is at steady state means that you don’t change weight…therefore you excrete the same amount you ingest
