Pathophysiology of Sodium Handling

Question 1

What is the most important factor that determines ECF volume?

Why?

Answer 1

Sodium!

• B/c sodium is the most abundant solute in the ECF

Question 2

1. What are the two main body fluid compartments?
2. One of the two main compartments is further subdivided into two more compartments, what are their names?

Answer 2

1. Intracellular fluid 28L (2/3 total body water) & Extracellular fluid 14L (1/3 total body water)
2. Extracelular fluid is further subdivided into:
   
   • Intravascular 3.5L (1/4) most important space
   • Extravascular 10.5L (3/4)

On average TBW = 42L

Question 3

T/F: Freely permeable solutes like urea (small molecule) affects water movement

Answer 3

• False, its freely permeable so no [] gradient forms

Question 4

What does the maintenence of ECF volume determine?

Answer 4

• Mean Arterial Pressure (MAP)
• Left ventricular filling volume

Question 5

What is effective arterial blood volume (EABV)?

Answer 5

EABV:

• Amount of arterial blood volume required to adequateley “fill” the capacity of arterial circulation

Question 6

• What type of receptors/sensors are found in the afferent limb?
  
  • Name the 4 types

Answer 6

Afferent limb: Volume Sensors

1. Low-pressure baroreceptors
2. High-pressure baroreceptors
3. Intrarenal sensors
4. Hepatic and central nervous system sensors

Question 7

Outline the location and function of low-pressure baroreceptors

Answer 7

Low-pressure baroreceptors:

• Location: Venous side of circulation (low pressure = venous)
• Function: Works to maintain venous return to the right side of the heart and CVP
  
  • Controls natriuresis and diuresis

Question 8

Outline the location and function of high-pressure baroreceptors

Answer 8

High pressure baroceptors:

• Location: High pressure = arterial circulation receptors
• Function: Works to maintain MAP
  
  • Controls diuresis and natriuresis, can also release catecholamines in severe volume contraction to increase HR and vascular resistance

Question 9

Outline the location and function of Intrarenal sensors

Answer 9

Intrarenal sensors:

• Location: Formed by the renal juxtaglomerular apparatus (JGA)
• Function: Control the release of renin
  
  • Changes in renal prefusion pressure, sodium chloride delivery to the JGA, and renal sympathetic nerves influence the release of renin

Question 10

What is found in the efferent limb of the homeostatic response?

Answer 10

Efferent limb: effector elements

Question 11

What are the 4 effector elements of the efferent limb?

Answer 11

1. Glomerular filtration
2. Physical factors at the level of the proximal tubula
3. Humoral effector mechanisms
4. Renal sympathetic nerves

Question 12

What is renal autoregulation?

Answer 12

Renal Autoregulation: Ability of the kidney to keep RBF (renal blood flow) and GFR constant

• Achieved by contraction of vascular smooth muscle of the stretched afferent arteriole in response to a higher intravsacular pressure or dilatation when perfusion pressure decreases

Question 13

What is tubuloglomerular feedback (TGF)?

Answer 13

TGF: Phenomenon whereby increased distal delivery of sodium chloride to the macula densa (art of the JGA) increases afferent arteriolar tone and returns the RBF and GFR towards normal values

Question 14

What is glomerulo-tubular balance?

Answer 14

Glomerulo-tubular balance: Changes in GFR automatically induce a proportional change (increase) in the rate of proximal tubular sodium reabsorption

• Therefore, fractional excretion of sodium is maintained constant in the setting of increases or decreases in GFR

Question 15

What are the 4 hormones that increase sodium reabsorption (antinatriuresis)?

Answer 15

1. Angiotensin II
2. Aldosterone
3. Catecholamines
4. Vasopressin

Question 16

What are the 4 hormones that decrease sodium reabsorption (natriuresis)?

Answer 16

1. Natriuretic peptides
2. Prostaglandins
3. Bradykinin
4. Dopamine

Question 17

Renal Sympathetic Nerves

1. What do the renal sympathetic nerves (RSN) innervate?
2. When RSN are activated what effect do they have on sodium balance?
3. What effect does RSN stimulation have on the RAAS pathway?

Answer 17

1. Iinnerevate: Afferent and efferent arterioles of the glomerulus
2. Activation = Anti-natriuretic effect
3. Stimulation = Release of renin from the JGA

*Note* “stimulation and activation” are synonyms not different processes just to be clear

Question 18

What percentage of the glomerular filtrate, including sodium, does the proximal tubule reabsorb?

Answer 18

• 60%

Question 19

What are the two sodium pumps in the proximal tubule?

Answer 19

• Na/K/ATPase
• Na/H

Question 20

What are the 4 major areas of sodium absorption in the kidney?

Answer 20

1. Proximal tubule
2. Thick ascending limb of the loop of Henle
3. Distal convoluted tubule
4. Principle cell of the cortial collecting duct

Question 21

T/F: The loop of henle is the site of most sodium reabsorption

Answer 21

FALSE

• Loop of Henle: 30% of filtered sodium is reabsorbed here
• Proximal Tubule: 60% of filtered sodium is reabsorpbed here

*Recognize: the site of major diuretic action is not at the site where the most sodium is reabsorbed in the body(*

Question 22

1. What is the main sodium transporter in the distal convoluted tubule?
2. What class of diuretics acts at this site?

Answer 22

1. Na/Cl cotransporter
2. Thiazides

Question 23

What are the two types of cells found in the Cortical Collecting Duct and what is their function?

Answer 23

1. Principal cells
   
   • Sodium/Potassium exchange
   • Reabsorb H₂0
2. Intercalated cells
   
   • Secretion of H⁺ & HCO₃^-

Question 24

What is the cardiovascular response to extracellular volume contraction?

Answer 24

• Increased sympathetic activity
  
  • Inc HR
  • Inc Inotropy
  • Inc Vascular Resistance
• Increased secretion of vasocontriction hormones
  
  • Angiotensin II, arginine vasopressin(AVP), endothelin

Question 25

What is the renal response to extracellular contraction?

Answer 25

* Dec GFR -\> smaller filtered load of sodium * Activation of renal sympathetic nerves * Vasocontriction of afferent arteriole and increased tubular re-abs of Na * Stimulation of RAAS * Inhibition of secretion of atrial natriuretic peptide (ANP) -\> anti-natriuretic effect

Question 26

What are the _clinical criteria_ for **Orthostatic Hypotension?**

Answer 26

* Decrease of \>10mmHg in SBP between supine and standing pressure _OR_ * Increase of \> 20bpm in heart rate upon standing * There may also be decreased elasticity (turgor) of the skin too

Question 27

What are the hemodynamic changes one would expect with instersitial fluid loss?

Answer 27

* Decreased * R atrial pressure * CVP * Pulmonary Capillary Wedge Pressure * CO * Increased * Systemic vascular resistance

Question 28

1. What is the BUN:Cr ratio c/w volume contraction? 2. pH wise, what would upper GI loss of fluid lead to? 3. pH wise, what would a lower GI loss of fluid lead to? 4. Would serum HCT & albumin be increased or decreased in volume contraction? 5. T/F: Urinary sodium will be high

Answer 28

1. _\>_ 20:1 2. Metabolic alkolosis (you are vomiting acidic gastic juices 3. Metabolic acidosis - You lose bicarb in diarrhea 4. Increased - due to hemoconcentration 5. False: it will be low, you want to retain sodium to inc your volume

Question 29

In what vascular compartment does edema form?

Answer 29

Interstitial compartment (recall: this is a sub compartment of the ECF)

Question 30

Distrurbed starling forces are one main mechanism of edema formation. * What are the 3 main examples of **disturbed starling forces that lead to edema**?

Answer 30

1. **R CHF** - inc venous pressure increases capillary hydrostatic pressure 2. **Nephrotic Syndrome** - urinary protein loss -\> decreased capillary oncotic pressure 3. **Cirrhosis** - hypoalbuminemia (due to malnutrition) & increased splanchnic vasodilation (seen in cirrhosis) cause both increased hydrostatic pressure and decreased oncotic pressure

Question 31

Primary hormone excess can also lead to edema formation. * What are the 3 main examples of **hormone overproduction leading to edema formation?**

Answer 31

1. **Primary hyperaldo** 2. **Cushing's syndrome** (hypercortisolism) 3. Syndrome of inapprorpirate secretion of anti-diuretic hormone **(SIADH)** _Recall:_ * Mineral corticoids promote Na+ reabsoprtion * Vasopressin promotes water reabsoprtion

Question 32

What disease results in **primary renal sodium retention that leads to edema**?

Answer 32

* Acute glomerulonephritis

Question 33

_Diuretics_ 1. What is the only diuretic that acts at the proximal tubule? 2. Name 3 diuretics that act at the Loop of Henle 3. What class of diuretics act at the distal convoluted tubule? 4. Name 3 diuretics that act at the collecting ducts

Answer 33

1. Acetazolamide 2. Furosemide; bumetanide, & torsemide 3. Thiazides (i.e. HCTZ) 4. Triamterene and amiloride, & spironolactone

Question 34

**T/F:** _The proximal tubule is responsible for 60% of the body's sodium reabsorption._ *Acetazolamide* which is acts at the proximal tubule is the *strongest diuretic available.*

Answer 34

* FALSE * Acetazolamide is a weak diuretic because the distal parts of the nephron compensate for the decrease in procimal reabsorption of Na+

Question 35

**T/F:** _Acetazolomide_ is a viable treatment for **metabolic alkylosis?**

Answer 35

* TRUE * **Acetazolamide** acts by blocking carbonic anhydrase action and **causes wastage of bicarb in the urine** * It can be _used to treat metabolic alkylosis_ when normal saline (NS) can't be given b/c of ECF volume expansion.

Question 36

What is the most potent (and therefore first line) class of diuretics?

Answer 36

* **Loop diuretics (act on the loop of Henl)** * **Inhibit the Na/2Cl/K co-transporter** * Recall 25% of sodium is reabsorbed here

Question 37

What are some of the major side effects of loop diuretics?

Answer 37

_Loop Diuretic Side Effects_ * **Hypokalemia** * **Metabolic alkalosis** * Hypocalcemia * Hypomagnesemia

Question 38

What is the mechanism of action of thiazide diuretics and what are their side effects?

Answer 38

_Thiazides_ * *Mechanism of Action* * **Block sodium entry across the apical membrane into distal tubular cells** * *Side effects* * **Metabolic alkalosis; hypokalemia, hypomagnesmia** * Note: unlike loop diuretics, _thiazides increase calcium reabsorption_

Question 39

1. What classes of diuretic are the ones that aact at the collecting ducts 2. What is the main benefit to these drugs?

Answer 39

1. * **Sodium Channel Blockers**: Triamterene & Amiloride * **Competitive Aldo Inhibitor:** Spironolactone * Can be used in states of secondary hyper aldo * e.g - cirrhosis with ascites 2. These diuretics can be used together with other classes of diuretics to **prevent hypokalemia**