Mechanisms to Adjust Urine Concentration Flashcards
A 65 y.o. man with a history of hypertension and a myocardial infarction 6 months ago presents to your cardiology clinic with complaints of shortness of breath and swollen ankles. Physical exam reveals 4+ pitting edema in the lower extremities, crackles and rales in both lungs, and jugular venous distention. You decide to treat his edema with a loop diuretic.
1.Is this a case of over or underfilling of the vascular tree?
Overfilling
•A 65 y.o. man with a history of hypertension and a myocardial infarction 6 months ago presents to your cardiology clinic with complaints of shortness of breath and swollen ankles. Physical exam reveals 4+ pitting edema in the lower extremities, crackles and rales in both lungs, and jugular venous distention. You decide to treat his edema with a loop diuretic.
1.How does this type of diuretic increase urine output?
Impair the ability of the medullary interstitium to become concentrated. Causing diuresis.
•A 65 y.o. man with a history of hypertension and a myocardial infarction 6 months ago presents to your cardiology clinic with complaints of shortness of breath and swollen ankles. Physical exam reveals 4+ pitting edema in the lower extremities, crackles and rales in both lungs, and jugular venous distention. You decide to treat his edema with a loop diuretic.
1.How can you determine if the diuretic is working properly?
Look for increased secretion of solutes. Via fractional excretion
Renal Control of Salt and Water Balance is crucial for the regulation of what things?
–Blood pressure
–Extracellular fluid solute concentration
–Concentrations of Na+, K+ in body fluids
Failure of Renal Control of Salt and Water Balance Can Cause…
(5)
- •Edema
- •Disorders of plasma K+ concentration: hyperkalemia, hypokalemia
- •Undesirable changes in blood pressure
- •Acid/base disorders
- •Neurological problems: shrinking or swelling of neurons
What are the Na+ reabsorption mechanisms for the following?
- Proximal tubule (50-55%):
- Thick ascending limb (35-40%):
- Early distal convoluted tubule (5-8%):
- Late distal convoluted tubule, collecting duct (2-3%):
- –Cotransport with glucose, amino acids, phosphate
–Countertransport with H+ (Na+/H+ exchange) - Na+, K+, 2Cl- cotransport
- Na+, Cl- cotransport
- luminal Na+ membrane channels
Water reabsorption is always passive, and can be either ______ or ______.
transcellular or paracellular
To what is Cl- reabsorption linked?
–Always linked, either directly or indirectly, to Na+ reabsorption (Cl- can balance the + charges)
Cl- movement in the proximal tubule is partially facilitatied by?
Leaky tight junctions
What impact does ADH have on the ascending limb of the loop of henle with regard to water?
None
What is the osmolarity of the tubular fluid entering the early distal tubule?
Hypoosmolar to plasma
What does aldosterone do in the Late DTC and collecting duct?
•Aldosterone stimulates Na+ reabsorption, K+ secretion, H+ secretion (H-ATPase) in this segment
What does ANP do in the late DTC and collecting duct?
•Atrial natriuretic peptide inhibits Na+ reabsorption (medullary collecting duct)
What does AVP do in the Late DCT and coll. duct?
•Antidiuretic hormone [arginine vasopressin (AVP)] stimulates water reabsorption
Where are principle cells located?
DCT and collecting duct
Permeability of Collecting Duct is Under Physiologic Control, describe the collecting duct in well hydrated individuals.
–Collecting duct is impermeable to water
–Water remains in tubular lumen; dilute urine is excreted
Permeability of Collecting Duct is Under Physiologic Control, describe the collecting duct in dehydrated individuals.
–Collecting duct is highly water-permeable
–Water is reabsorbed; low volume of concentrated urine is excreted
Inner medullary interstitial fluid has very high solute concentration but low blood flow. Why is low blood flow beneficial for being able to concentrate our urine?
Prevents washing out the gradient.
What does the countercurrent multiplier mechanism do?
•Concentrates solutes in medullary interstitium
What are the 3 components the countercurrent multiplier relies upon?
–Descending, ascending limbs of Henle’s loop
–Vasa recta capillaries
–Collecting ducts
What impact does a high protein diet have on urine concentration?
Individuals who consume high protein diets can concentrate their urine much better than those with low protein diets.
What would likely happen in a case of excess ECF volume?
- No ADH
- Increased RBF
- Increased GFR
- Decreased urea recycling (lower concentration since more H2O is present)
- Urea excretion
- Less concentrated urine
How do vasa recta contribute to the countercurrent?
•Vasa recta are countercurrent exchangers
–Highly permeable to solutes and water
–Equilibrate with medullary interstitium
–Vasa recta don’t create the medullary hyperosmolarity, but they do maintain it (prevent it from being dissipated)!
•Osmotic Diuretics:
decrease water reabsorption by increasing osmotic pressure of tubular fluid
•Loop Diuretics:
decrease activity of Na-2Cl-K cotransport and reabsorption in the thick ascending loop of Henle
–Disruption of countercurrent multiplier system
–Increase delivery of solutes to distal nephron segments, which act as osmotic agents to prevent water reabsorption
Thiazide Diuretics
•Thiazide Diuretics: decrease NaCl reabsorption in the early distal tubule
What do you think happens to K+ balance with these types of diuretics?
Osmotic, loop and thiazide diuretics
may promote potassium secretion. Can give potassium sparing diuretics to offset this impact.
•Carbonic Anhydrase Inhibitors:
block sodium bicarbonate reabsorption in the proximal tubule
–The decrease in Na+ and HCO3- reabsorption causes osmotic diuresis (disadvantage is that these can cause acidosis)
•Competitive Inhibitors of Aldosterone:
decrease Na+ reabsorption from and K+ secretion into the cortical collecting tubule
–Na+ remains in the tubules and acts as an osmotic diuretic
–Can cause increased ECF K+ levels (potassium-sparing diuretics)
What triggers of antidiuresis did we talk about? What are these mediated by?
•Osmoreceptor-ADH Feedback System
–Increased ECF osmolarity causes osmoreceptor cells in the hypothalamus to shrink, leading to ADH secretion
•Decreased arterial pressure leads to ADH secretion
–Aortic arch and carotid sinus baroreceptors
•Decreased blood volume leads to ADH secretion
–Cardiac atria
•strong stimuli for ADH secretion are also strong stimuli for?
thirst (+ Angiotensin II)
What is the formula for the Obligatory Urine Volume
(Water Loss)
What is the formula for osmolar clearance?
•Osmolar clearance (Cosm) = (Uosm · V) / Posm
What is the formula for free water clearance?
CH2O = V – Cosm
V=urine flow
Cosm= osmotic clearance
If Uosm < Posm, CH2O is
positive; pure water is cleared from the body
•If Uosm > Posm, CH2O is
negative; pure water is retained
•Does AVP affect CH2O?
Yes
What is the formula for fractional excretion?
!!!!!!Must know this equation!!!!!
–Fex = (Ux * Pcr) / (Px * Ucr)
Where Cr is creatinine
Be able to figure this out based on these values and others, including inulin potentially.
What could cause a decreased fractional excretion?
Increased reabsorption
What are three types of Disorders of Urinary Concentrating Ability?
1.Inappropriate secretion of ADH
–Central Diabetes Insipidus: failure to produce ADH
- SIADH: Ectopic foci of continuous ADH production
2.Impairment of the countercurrent mechanism
–No matter how much ADH is present, maximal urine concentraiton is limited by the degree of hyperosmolarity of the medullary interstitium.
3.Inability of the distal tubule, collecting tubule, and collecting duct to respond to ADH
–Nephrogenic Diabetes Insipidus: inability of the kidneys to respond to ADH
How do you tell what kind of diabetes insipidus a patient has?
Give them ADH. If central diabetes insipidus, they will improve.
If nephrogenic, then they will not respond to ADH
How does increased RBF impact osmolarity?
–Increases flow through the vasa recta and washes out solutes from the renal medulla
How does increased GFR impact osmolarity?
–Increased tubular flow, active transport of Na+ is not able to sufficiently dilute the tubular fluid in the TAL, and urea is not as concentrated in the collecting tubule (due to water being present). This decreases the medullary hyperosmolarity.
How does the absence of ADH impact osmolarity?
–Cortical CD and outer medullary CD, and initial part of the inner medullary CD become impermeable to water and urea does not get concentrated, reducing urea reabsorption from the terminal part of the collecting duct by ~20%
