Physiology Block 7 Lectures 21-24

Example of organic cations that are secreted in the proximal tubule?

CREATININE, dopamine, epinephrine, norepinephrine, and drugs (atrophine, morphine, sympathomimetics)

How do Starling forces change as you go from glomerular capillary to peritubular capillary?

Capillary hydrostatic pressure drops as it flows across efferent arteriole, while tubular hydrostatic pressure rises in comparison. Capillary oncotic pressure also rises because so much water filtered out at the glomerular capillary (increases concentration of proteins). Although Starling forces at the glomerular capillary favor filtration, these changes cause reabsorption to be favored at the peritubular capillary.

What happens to capillary hydrostatic and oncotic pressures when renal blood flow increases?

Capillary hydrostatic pressure increases in proportion to the increase in renal blood flow. Capillary oncotic pressure does not rise this much though. This means that when renal blood flow increases, filtration will increase and reabsorption will decrease. (If oncotic pressure increased just as much as hydrostatic pressure increased, there would be no change in filtration or reabsorption.)

Describe how Na+ and Cl- are reabsorbed paracellularly in the late proximal tubule.

Chloride concentration in the lumen is high in the later proximal tubule because it was not reabsorbed in the early tubule (whereas a lot of water was). This not only drives Cl- transport transcellularly, but also paracellularly. This massive reabsorption of Cl- causes a slightly positive intraluminal charge, which also drives Na+ paracellular reabsorption.

T/F: Water movement in the kidneys may be by passive or active processes.

False. All water movement is passive.

T/F: To reabsorb more water, you would want to excrete more solutes.

False. Water moves by osmotic influences, so if you excrete more solutes, more water is going to follow and be excreted as well (called "osmotic diuresis").

T/F: The reabsorption of water in the proximal tubule is influenced by hormones.

TRUE. Although hormones do not change the permeability of water in the proximal tubule, they can affect transport of solutes, renal blood flow, and capillary pressure, all of which would influence the reabsorption of water.

T/F: Half of the transport in the thick ascending loop of Henle is paracellular.

TRUE. This is because there is high reabsorption of chloride and bicarbonate, which further increase the positive potential in the lumen. This positive potential drives cations (Na, K, Ca, Mg) to be reabsorbed by paracellular transport. THIS IS ESPECIALLY TRUE FOR POTASSIUM.

What kinds of substances should never be found in the urine of a healthy individual?

GLUCOSE, amino acids, protein, blood, leukocytes, bilirubin, ketones, bacteria

How does high GFR affect tubular load of sodium? How does this influence JGA activity?

High GFR means increased filtration, so greater tubular load of sodium. This decreases JGA secretion of renin, and thus RAAS activity.

What kinds of influences would cause water to move to a different area?

Hydrostatic pressure or osmotic influences (solutes)

Is ADH secretion more sensitive to hypernatremia or hypovolemia?

Hypernatremia - unless in hypovolemic shock, in which case ADH will be secreted even if it does mess up plasma osmolarity

What effect would hypothyroidism have on serum phosphate levels? Why?

Hypothyroidism would cause hypophosphatemia. Hypothyroidism --> decreased metabolism --> decreased function of basolateral Na/K ATPase --> decreased function of Na/phosphate symporter (by secondary active transport). Decreased metabolism causes more sodium to be excreted, which causes more phosphate to be excreted. This would also cause osmotic diuresis --> hypotension.

T/F: ADH controls concentration of sodium, but not content of sodium. Aldosterone controls content of sodium, but not concentration of sodium.

True

T/F: Renin secretion is increased by decreased GFR.

True

T/F: There is no active transport of solutes in the thin descending limb of the Loop of Henle.

True. However, water permeability here is high.

T/F: The volume of tubular fluid does not change in the early distal tubule.

True. This is because the early distal tubule is impermeable to water.

T/F: The osmolarity of the tubular fluid in the thick ascending loop of Henle drops below the normal plasma osmolarity.

True. This is because this segment is impermeable to water, so solutes are being reabsorbed while water stays in the tubular fluid. Solute reabsorption here raises interstitial osmolarity to very high concenctrations (1200 mOsm/L).

Why is vasa recta function critical to production of a concentrated urine?

Vasa recta flow removes solutes from the medulla, which allows solutes to be reabsorbed from the tubular fluid (thus producing dilute urine).

Baroreceptor input (inhibits/stimulates) secretion of ADH.

inhibits

What are the two principal control mechanisms for secretion of aldosterone? Which is it more sensitive to?

plasma potassium concentration (more sensitive stimulator) and plasma angiotensin II concentration

ADH binds to the ____ receptor in order to regulate the water channel, ____, in the collecting duct.

vasopressin 2 (V2) receptor Aquaporin 2 (AQP2) channel

If FL<Tm, then excretion will = ?

zero. If filtered load is less than transport maximum, then all of that solute can be reabsorbed without any being excreted.

Water and solutes pass through _____ during paracellular transport.

tight junctions

Most reabsorption of sodium is (transcellular/paracellular).

transcellular

Indicate whether ADH would increase or decrease the following... 1. urine flow 2. urine osmolarity 3. plasma osmolarity 4. ECF volume

1. decrease 2. increase 3. decrease 4. increase

Indicate whether high sodium intake would cause an increase or decrease of the following by compensation... 1. sympathetic activity 2. ANP secretion 3. RAAS activity 4. TPR

1. decrease 2. increase - because of high preload 3. decrease - because of higher tubular load of sodium 4. decrease - because increased water reabsorption causes higher cardiac output - decrease TPR to prevent MAP from skyrocketing

Indicate whether aldosterone would increase or decrease the following... 1. blood volume 2. plasma potassium 3. plasma sodium 4. renal excretion of acid 5. blood pH

1. increase 2. decrease 3. increase 4. increase 5. increase

What hormones directly regulate permeability of water in the late distal tubule and collecting duct?

ADH (increases) and ANP (decreases)

How does alcohol consumption affect ADH secretion?

Alcohol inhibits secretion of ADH.

How can aldosterone influence reabsorption of chloride?

Aldosterone stimulates increased reabsorption of sodium from tubular fluid. Taking these cations out of the fluid produces a relatively negative potential in the lumen, which drives the negatively charged chloride to be reabsorbed by paracellular transport.

Aldosterone tends to produce metabolic (acidosis/alkalosis). Why?

Alkalosis. Part of aldosterone's mechanism is to stimulate active secretion of H+ (acid). Bicarbonate will also be reabsorbed. The combination of these two produce metabolic alkalosis.

What part(s) of the nephron is(are) impermeable to water?

Ascending loop of Henle, early distal tubule

Where in the nephron does the majority of sodium (and thus water) reabsorption occur?

In the proximal tubule (2/3 of the total amount reabsorbed)

With high sodium intake, would you want to compensate by increasing or decreasing GFR? What combination of afferent/efferent dilation/constriction would help best promote this? (Ex. afferent constriction with efferent dilation)

Increase GFR to get rid of excess sodium Dilation of afferent arteriole with constriction of efferent arteriole would both increase GFR

Will vasa recta flow increase or decrease with high water consumption?

Increase. This increases reabsorption of solutes and produces a dilute urine.

ADH (increases/decreases) reabsorption of urea.

Increases. ADH also increases permeability of the collecting duct to water.

Where in the nephron does aldosterone have its greatest effect? What is its mechanism?

Late distal tubule and cortical collecting duct: increases apical permeability of sodium (reabsorption) and potassium (secretion); increases activity of Na/K ATPase on basolateral surface; increases activity of active H+ secretion on apical surface

Describe how Na+ and Cl- are reabsorbed by transcellular transport in the late proximal tubule.

Na+ is reabsorbed via the Na/H exchanger, and Cl- is reabsorbed via the Cl/anion exchanger. When the anion and H+ are pumped out, they join in the lumen, passively diffuse back into the cell, break apart, and then allow for the two exchangers to go again. This is a very efficient way to reabsorb Na+ and Cl-, because it just keeps cycling.

What is the unique transporter on the apical surface of the thick ascending loop of Henle? What powers this transporter?

Na/K/2Cl symporter - secondary active transporter powered by high intraluminal chloride and low intracellular sodium

What is solvent drag?

Not only do osmotic gradients encourage water movement, but when this water moves it also carries solutes with it (K+, Ca++, etc.) -- this is called solvent drag.

Explain how PAH secretion involves tertiary active transport. What other anions are secreted this way?

PAH enters cells by antiport with tricarboxylate (alpha-ketoglutarate). High intracellular tricarboxylate concentration gradient built by symport with sodium. Low intracellular sodium gradient built by Na/K ATPase. So, PAH enters by tertiary active transport. Other anions are secreted similarly, such as urate, cAMP, bile salts, prostaglandins, penicillin, and aspirin.

What are the two types of transport in the nephron? Are these active or passive?

Paracellular (passive) or transcellular (active or passive)

Describe how amino acids are reabsorbed in the early proximal tubule.

Reabsorbed with Na+ via a symporter on the apical surface, which is secondary active transport. The energy to perform this action is the low concentration gradient of sodium within the cell, a gradient which is formed by the Na+/K+ ATPase on the basolateral surface.

What is the largest contributor to osmotic influences on water movement?

Reabsorption of sodium with chloride and organic solutes

Which part of the loop of Henle is termed the "diluting segment"?

The thick ascending loop - because solutes are reabsorbed but the tube is impermeable to water reabsorption. Water stays in tubular fluid but solutes leave --> diluting urine

Osmoreceptors that regulate ADH secretion are located in the ______.

anterior ventral surface of the 3rd ventricle (AV3V)