Pathophysiology of Sodium Handling Flashcards
What is the most important factor that determines ECF volume?
Why?
Sodium!
- B/c sodium is the most abundant solute in the ECF
- What are the two main body fluid compartments?
- One of the two main compartments is further subdivided into two more compartments, what are their names?
- Intracellular fluid 28L (2/3 total body water) & Extracellular fluid 14L (1/3 total body water)
- Extracelular fluid is further subdivided into:
- Intravascular 3.5L (1/4) most important space
- Extravascular 10.5L (3/4)
On average TBW = 42L
T/F: Freely permeable solutes like urea (small molecule) affects water movement
- False, its freely permeable so no [] gradient forms
What does the maintenence of ECF volume determine?
- Mean Arterial Pressure (MAP)
- Left ventricular filling volume
What is effective arterial blood volume (EABV)?
EABV:
- Amount of arterial blood volume required to adequateley “fill” the capacity of arterial circulation
- What type of receptors/sensors are found in the afferent limb?
- Name the 4 types
Afferent limb: Volume Sensors
- Low-pressure baroreceptors
- High-pressure baroreceptors
- Intrarenal sensors
- Hepatic and central nervous system sensors
Outline the location and function of low-pressure baroreceptors
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
Outline the location and function of high-pressure baroreceptors
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
Outline the location and function of Intrarenal sensors
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
What is found in the efferent limb of the homeostatic response?
Efferent limb: effector elements
What are the 4 effector elements of the efferent limb?
- Glomerular filtration
- Physical factors at the level of the proximal tubula
- Humoral effector mechanisms
- Renal sympathetic nerves
What is renal autoregulation?
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
What is tubuloglomerular feedback (TGF)?
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
What is glomerulo-tubular balance?
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
What are the 4 hormones that increase sodium reabsorption (antinatriuresis)?
- Angiotensin II
- Aldosterone
- Catecholamines
- Vasopressin
What are the 4 hormones that decrease sodium reabsorption (natriuresis)?
- Natriuretic peptides
- Prostaglandins
- Bradykinin
- Dopamine
Renal Sympathetic Nerves
- What do the renal sympathetic nerves (RSN) innervate?
- When RSN are activated what effect do they have on sodium balance?
- What effect does RSN stimulation have on the RAAS pathway?
- Iinnerevate: Afferent and efferent arterioles of the glomerulus
- Activation = Anti-natriuretic effect
- Stimulation = Release of renin from the JGA
*Note* “stimulation and activation” are synonyms not different processes just to be clear
What percentage of the glomerular filtrate, including sodium, does the proximal tubule reabsorb?
- 60%
What are the two sodium pumps in the proximal tubule?
- Na/K/ATPase
- Na/H
What are the 4 major areas of sodium absorption in the kidney?
- Proximal tubule
- Thick ascending limb of the loop of Henle
- Distal convoluted tubule
- Principle cell of the cortial collecting duct
T/F: The loop of henle is the site of most sodium reabsorption
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(*
- What is the main sodium transporter in the distal convoluted tubule?
- What class of diuretics acts at this site?
- Na/Cl cotransporter
- Thiazides
What are the two types of cells found in the Cortical Collecting Duct and what is their function?
- Principal cells
- Sodium/Potassium exchange
- Reabsorb H20
- Intercalated cells
- Secretion of H+ & HCO3-
What is the cardiovascular response to extracellular volume contraction?
-
Increased sympathetic activity
- Inc HR
- Inc Inotropy
- Inc Vascular Resistance
-
Increased secretion of vasocontriction hormones
- Angiotensin II, arginine vasopressin(AVP), endothelin
What is the renal response to extracellular contraction?
- 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
What are the clinical criteria for Orthostatic Hypotension?
- 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
What are the hemodynamic changes one would expect with instersitial fluid loss?
- Decreased
- R atrial pressure
- CVP
- Pulmonary Capillary Wedge Pressure
- CO
- Increased
- Systemic vascular resistance
- What is the BUN:Cr ratio c/w volume contraction?
- pH wise, what would upper GI loss of fluid lead to?
- pH wise, what would a lower GI loss of fluid lead to?
- Would serum HCT & albumin be increased or decreased in volume contraction?
- T/F: Urinary sodium will be high
- > 20:1
- Metabolic alkolosis (you are vomiting acidic gastic juices
- Metabolic acidosis - You lose bicarb in diarrhea
- Increased - due to hemoconcentration
- False: it will be low, you want to retain sodium to inc your volume
In what vascular compartment does edema form?
Interstitial compartment (recall: this is a sub compartment of the ECF)
Distrurbed starling forces are one main mechanism of edema formation.
- What are the 3 main examples of disturbed starling forces that lead to edema?
- R CHF - inc venous pressure increases capillary hydrostatic pressure
- Nephrotic Syndrome - urinary protein loss -> decreased capillary oncotic pressure
- Cirrhosis - hypoalbuminemia (due to malnutrition) & increased splanchnic vasodilation (seen in cirrhosis) cause both increased hydrostatic pressure and decreased oncotic pressure
Primary hormone excess can also lead to edema formation.
- What are the 3 main examples of hormone overproduction leading to edema formation?
- Primary hyperaldo
- Cushing’s syndrome (hypercortisolism)
- Syndrome of inapprorpirate secretion of anti-diuretic hormone (SIADH)
Recall:
- Mineral corticoids promote Na+ reabsoprtion
- Vasopressin promotes water reabsoprtion
What disease results in primary renal sodium retention that leads to edema?
- Acute glomerulonephritis
Diuretics
- What is the only diuretic that acts at the proximal tubule?
- Name 3 diuretics that act at the Loop of Henle
- What class of diuretics act at the distal convoluted tubule?
- Name 3 diuretics that act at the collecting ducts
- Acetazolamide
- Furosemide; bumetanide, & torsemide
- Thiazides (i.e. HCTZ)
- Triamterene and amiloride, & spironolactone
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.
- FALSE
- Acetazolamide is a weak diuretic because the distal parts of the nephron compensate for the decrease in procimal reabsorption of Na+
T/F: Acetazolomide is a viable treatment for metabolic alkylosis?
- 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.
-
Acetazolamide acts by blocking carbonic anhydrase action and causes wastage of bicarb in the urine
What is the most potent (and therefore first line) class of diuretics?
-
Loop diuretics (act on the loop of Henl)
- Inhibit the Na/2Cl/K co-transporter
- Recall 25% of sodium is reabsorbed here
What are some of the major side effects of loop diuretics?
Loop Diuretic Side Effects
- Hypokalemia
- Metabolic alkalosis
- Hypocalcemia
- Hypomagnesemia
What is the mechanism of action of thiazide diuretics and what are their side effects?
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
- What classes of diuretic are the ones that aact at the collecting ducts
- What is the main benefit to these drugs?
- Sodium Channel Blockers: Triamterene & Amiloride
-
Competitive Aldo Inhibitor: Spironolactone
- Can be used in states of secondary hyper aldo
- e.g - cirrhosis with ascites
- Can be used in states of secondary hyper aldo
- These diuretics can be used together with other classes of diuretics to prevent hypokalemia
