Week 9 Flashcards
Discuss the direct renal influences in a patient who has been stabbed to stabilize his blood volume and pressure.
- Increase extracellular fluid volume: The patient has lower blood volume which causes decreased blood pressure. This decreases blood perfusion to the kidneys, causing them to retain water in efforts to increase total body fluid by increasing renin production.
- Increased erythropoietin production to increase red blood cell production
- increase cardiac performance
- ECF Osmolality
- Increase total peripheral resistance
Map the concept of renin-angiotensin-aldosterone system
§ Renin–> converts angiotensinogen–> angiotensin I–> angiotensin I is converted to angiotensin II by ACE in the lung tissue–> has a number of effects like vasoconstriction, Na+ reabsorption, water reabsorption, and increase thirst (see diagram below).
physiologic actions of Angiotensin II in regulation of blood volume and pressure.
- vasculature
- efferent arterioles
- water reabsorption
- sodium reabsorption
- thirst
- Angiotensin II acts on AT1 receptors located on vascular smooth muscle to induce vasoconstriction–> increases peripheral resistance–> increases blood pressure.
- Angiotensin II constricts efferent arterioles of the glomerulus to preserve renal function
- increases aldosterone secretion from the adrenal glands to increase sodium and water reabsorption.
- increases water reabsorption by increasing ADH release from the posterior pituitary.
- Angiotensin II also increases the activity of renal transporters in the thick ascending limb. So, the sodium/potassium pump activity increases–> causing sodium reabsorption. Increased activity of other renal transporters also increase resorption of bicarb and water.
- Other factors increase thirst by stimulating the hypothalamus
If a patient is euvolemic and he consumes 100 mEq/day of Na how much Na would he excrete?
- Since he is already euvolemic, he would lose 100 mEq/day.
Parts of Na reabsorption
So when there is normal ECF volume, GFR will be normal. And so, 92% of the filtered sodium is reabsorbed by the proximal tubule and thick ascending limb. The constant portion of the filtered sodium (8%) is delivered to the distal tubule. This is how sodium reabsorption by the distal tubule is regulated so that the amount of sodium excreted matches the amount ingested in the diet.
Discuss if the regulatory signal is increased or decreased in volume expansion vs Volume depletion
- Renal Sympathetic activity
- ANP and BNP
- Capillary Oncotic pressure
- Angiotensin II
- Aldosterone
- ADH lecels
- Na reabsorption
- VE: d; VD: i
- VE: i; VD: d
- VE: d; VD: i
- VE: d; VD: i
- VE: d; VD: i
- VE: d; VD: i
- VE: d; VD: i
What are the effects of ANP
ANP causes a loss of sodium into the urine, resulting in diuresis because water is also lost with it.
countercurrent multiplier & exchanger from the diagram?
○ Urea recycling & the exchanger is the vasa recta
countercurrent mechanism
- what is it used for
○ Maintaining osmolality across the vasa recta, the interstitium, & the urine tubule, but we’re increasing the concentration of the urine during that time
main diuretics that have their site reaction in the PCT
- Acetazolamide–carbonic anhydrase inhibitors
- Osmotic diuretics
- Adenosine
What are the main diuretics that have their sit reaction in the Thin descending limb
Osmotic agents
What are the main diuretics that have their sit reaction in the thick ascending limb
Loop diuretics
What are the main diuretics that have their sit reaction in the DCT
Thiazides
What are the main diuretics that have their sit reaction in the Collecting tubules
○ Aldosterone antagonists
○ ADH antagonists lower in the collecting tubule
Carbonic Anhydrase Inhibitors
- example
- function
- side effect
○ acetazolamide
- inhibit the carbonic anhydrase action, both in the luminal side & within the cell, but the more important factor is the luminal side. The major factor is it’s going to increase HCO3 excretion.
- more HCO3 excretion can lead to acidosis
Loop Diuretics
- MOA
- potassium recycling
- side effects
- direct effect to inhibit the NKCC2 on the luminal side & be doing that you directly increase urine Na & Cl. Also by inhibiting that same NKCC2 channel you have a small increase in urine potassium
- disturb their potassium recycling, which is going to cause an increase in calcium & magnesium in the urine.
- inhibiting salt reabsorption in the loops increase Na delivery to the collecting ducts & it’s the Na there that will change K & H absorption for reabsorption; that’s how you end up becoming more alkalotic–more basic
Loop + Thiazide
- why use combo?
- side effects
- benefits
- both of these drugs individually could have a resistance build up against them by having increased Na reabsorption through other channels etc. But when you use both of them there’s a synergy & all the channels are blocked so all the Na is excreted. So there’s a lot more excretion & a lot more of that diuresis effect. That’s the big reason why you would use both in synergy
- The changes in Na with the loops & thiazide combined you have an even larger increase in urine Na, so that’s going to cause an increase in K & H going into the urine.
○ Using these drugs in combination might negate the calciuremia that’s invoked by the loop diuretics bc the thiazides will actually increase Ca in the blood
Thiazide
- MOA
- where does it work?
- what happens to Cl
- what happens to Ca
- how does it cause alkalosis
○ Inhibits Na Cl transporter.
- It’s going to work at the early DCT, so Na remains in the lumen → increase in urine output.
- Cl is going to stay in the lumen & the Na downstream enters the DCT then the Na channels, and the lumen develops a negative charge to it causeing H+ ions to enter the cell
○ increase in Ca reabsorption bc decreased Na in cell causes upregulation of the NaCa antiporter so more Ca’s gonna go into the blood
- increased Na concentration in the urine increases H & K movement in the collecting tubule and if H goes into lumen BiCarb has to go into blood causing alkalosis
Aldosterone antagonists
- what does this do to K?
- ex?
- MOA
- side effects
- another type
○ Potassium sparing diuretics
○ Ex: Spironolactone
○ Competitive aldosterone receptor antagonists in the cortical collecting tubules. They act mainly in the principle cell & alpha intercalated cells.
○ At the principle cells we said that by blocking that it prevents mainly K secretion, At the intercalated cell it’s going to prevent H secretion -> hyperkalemia or acidosis
○ Amiloride is another aldosterone antagonist & it works by blocking the ENaC channels. So it’s a similar mechanism in the sense that the end result is the same, but how you get there is either through receptor or blocking the ENaC channel
How does ADH work?
- where?
- other effects
- Works at distal convoluted tubule and collecting duct
- Binds V2 receptor -> Increases cAMP concentration and ultimately increases incorporation of aquaporin 2 channels on apical membrane to increase water reabsorption
- Also binds V1 on blood vessels causes vasoconstriction to increase SVR and cause increased arterial pressure
Relationship of diabetes and ADH
- vs central pathology
- differences in treatment
ADH level can be normal or increased but there is resistance to ADH by the kidney, so no response from kidney to ADH
- there’s a deficiency in ADH
- case of central -> you’d give an ADH agonist ; For nephrogenic, you’d give a thiazide because it will cause hyponatremia which could correct the patient’s hypernatremia and decrease the polyuria the patient is experiencing; An NSAID like indomethacin would inhibit prostaglandin which would stop inhibition of ADH, so that would increase vasoconstriction
How to differentiate central and nephrogenic based on the water deprivation test and desmopressin?
- Water deprivation test in central and nephrogenic: no change in urine osmolality
- In response to ADH, increased urine osmolality in central and no change in nephrogenic
3 major factors that concentrate the urine?
- ADH
- Renal response to ADH
- Medullary tonicity
