Regulating Body Fluid Osmolality Flashcards
What happens to the medullary salt gradient when blood flow through the vasa recta increases?
Medullary Washout
Vasa recta removes salt and water continuously added to the medullary interstitium
If blood flow through the vasa recta increases, more salt and water are removed, dissipating the medullary gradient
What affect does reducing vasa recta blood flow have on urine production?
Decreasing the blood flow through the vasa recta will decrease the amount of salt and solute transport out of the nephron lumen in the medulla, thus reducing the ability to concentrate urine
Which segments of the nephron are nearly impermeable to urea?
Thick ascending limb of the loop of henle
Distal Convoluted Tubule
Cortical Collecting Duct
What transporters allow for urea diffusion into the interstitium from the medullary collecting duct?
UT-A1 and UT-A3
How is urea recycled?
Urea removed from the medullary collecting duct by diffusion into the medullary interstitium.
Some urea in the interstitium is secreted into the descending limb of the loop of henle with the help of the UT-A2 transporter where then starts to travel through the nephron once again (recycled)
What is another name for ADH?
AVP (arginine vasopressin)
How does ADH signaling function?
ADH is synthesized and stored in secretory vesicles in two types of large neurons in the hypothalamus (supraoptic and paraventricular neurons)
Supraoptic and Paraventricular nuclei in the hypothalamus are stimulated by increased osmolarity and other factors, which causes nerve impulses to [ass down these nerve endings, changing the membrane permeability and increasing Ca2+ entry
ADH stored in secretory vesicles at the nerve endings are released.
What signals are osmoreceptors responsible for and which comes first?
Osmoreceptors are sensitive to small changes (1-2%) in plasma osmolality, resulting in ADH secretion and thirst stimulation
ADH secretion occurs rapidly in response to osmoreceptor activation, and thirst sensation comes somewhat later
What are the two cell types found in the late distal convoluted tubule and collecting duct, and what makes them different?
Principal Cells: Reabsorb Na+, Cl-, H2O and Secrete K+
- Contain intracellular aldosterone receptor
- Have surface ADH receptor on basolateral membrane
- Have Na/K ATPase on basolateral membrane (Na+ pumped into interstitium, K+ pumped into cell)
- H2O reabsorbed in response to ADH signaling (Aquaporin-2 Channels)
- Na+ reabsorption happens via Na/K ATPase depleting intracellular Na+, allowing the passive movement of Na+ across the luminal membrane into the cell
- K+ uptake across basolateral membrane via Na/K ATPase, and diffuse across luminal membrane down its concentration gradient
What is the function of Principal Cells?
Overall: Reabsorb Na+, Cl-, H2O and Secrete K+
- Contain intracellular Aldosterone receptor
- Have surface ADH receptor on basolateral membrane
- Have Na/K ATPase on basolateral membrane (Na+ pumped into interstitium, K+ pumped into cell)
- H2O reabsorbed in response to ADH signaling (Aquaporin-2 Channels)
- Na+ reabsorption happens via Na/K ATPase depleting intracellular Na+, allowing the passive movement of Na+ across the apical (luminal) membrane into the cell
- K+ uptake across basolateral membrane via Na/K ATPase, and diffuse across apical membrane down its concentration gradient
- Cl- is reabsorbed paracellularly
What is the function of Intercalated Cells?
Overall: Reabsorb K+; Secrete H+
- Aldosterone increases H+ secretion by stimulating H-ATPases on the apical membrane
- Reabsorb K+ by an H+/K+ ATPase on the apical membrane
- Basolateral Membrane has a HCO3-/Cl- exchanger that sends HCO3- into the renal interstitium, while bringing Cl- into the intercalated cell
What are the two types of diabetes insipidus?
Central “neurogenic” Diabetes Insipidus
Nephrogenic Diabetes Insipidus
What is Central “Neurogenic” Diabetes Insipidus?
Inability to produce or release ADH from the posterior pituitary
Can be caused by head injuries, infections, or congenital
Without ADH, distal tubular segments cannot reabsorb water, which results in dilute urine production with volume that exceeds 15 L/day
Treated with synthetic analogue of ADH, called Desmopressin.
What is Nephrogenic Diabetes Insipidus?
Inability of kidneys to respond to ADH
Either due to issues with countercurrent mechanism forming hyperosmotic renal medullary interstitium OR issues with distal and collecting tubules and collecting ducts responding to ADH
In both, excessive volume of dilute urine is produced
Diuretics affecting salt reabsorption in the loop of henle can make symptoms worse
So does lithium and tetracylcines (which impair distal nephron segments response to ADH)
How do you determine which form of Diabetes Insipidus a patient has?
By administering Desmopressin.
If within 2 hours, there is no prompt decrease in urine ouput and increase urine osmolarity, then nephrogenic diabetes insipidus is the likely form.
If proper response occurs, then patient has Central “neurogenic” diabetes insipidus
What is SIADH?
Syndrome of Inappropriate ADH
Excessive release of ADH leading to excessive water retention (even when the body doesn’t need to be retaining water)
Increased water retention leads to increased ECF
Increased ECF leads to decreased plasma osmolality, hyponatremia, diminished Aldosterone secretion (since it is reponsive to increased levels of serum K+), and elevated glomerular filtration rate (GFR)
Increased sodium excretion leads to fluid shifting into cells
Pt develops thirst, dyspnea on exertion, vomiting, abdominal cramps, confusion, lethargy,and hyponatremia
What urine volume is considered normal?
1-2 L/day
What urine volume is considered Polyuria?
> 2.5 L/day
What urine volume is considered Oliguria?
300-500 mL/day
What urine volume is considered Anuria?
< 50 mL/day
What is the Ratio of Urine Osmolality and what does it tell us?
Ratio of Urine Osmolality is the ratio of Urine Osmolality (Uosm) to Plasma Osmolality (Posm).
Uosm:Posm ratio greater than 1 indicates kidneys are able to concentrate urine
Uosm:Posm ratio of 1 indicates water and solute are being excreted in a state that is iso-osmotic with plasma
Uosm:Posm ratio significantly less than 1 indicates kidneys are able to dilute urine
What would be the result of infusing a drug that inhibits Na-K-ATPase activity?
Osmotic diuresis
What is wrong with a patient that has lost weight, Plasma Na+ and Plasma osmolality are reduced, and kidneys excrete concentrated urine?
Excessive ADH secretion
What is the most significant contribution of the Loop of Henle in regard to urine concentration/dilution?
Actively reabsorbing Na+ and Cl-
What is the primary factor that determines long-term (over days) output of urine via kidney?
The volume of total fluid intake
In a steady state, fluid intake must equal fluid output. Regulatory systems adjust output to match input.
