Physiology-Control and Composition of Body Fluids

Question 1

What things does the kidney try to control?

Answer 1

Water, Na, K, Ca, P, Mg and Acid-Base

Question 2

A storm hits your city really hard and you get snowed in. All you have to eat is potato chips and water storage. Why might you see a weight gain after eating your emergency food supply for a couple of days?

Answer 2

As you increase sodium intake, your body tries to maintain a constant plasma osmolarity. With increased salt intake, you must retain more water to maintain the same osmolarity and will gain water weight.

Question 3

How does the body assess its water content?

Answer 3

Plasma osmolarity and the Effective Circulating Volume (fullness of vascular system)

Question 4

Where are plasma osmolarity receptors and baroreceptors found in the body?

Answer 4

Osmoreceptors = Hypothalamus. Baroreceptors = Aortic arch and carotid sinus.

Question 5

You’re hungry for your morning snack and grab a bag of chips. While pounding the chips you ingest 9g of NaCl. How does your body respond to this?

Answer 5

This will increase plasma osmolarity by about 3%. The hypothalamus will sense this and send a signal to the pituitary gland to release more ADH (10x) in response to the increase in plasma osmolarity. Osmoreceptor stimulation also increases the thirst reflex. These two consequences = increased H2O intake & decreased H2O excretion

Question 6

What kind of change do you need in the effective circulating volume in order to get the same increase in ADH seen in changes with osmolarity?

Answer 6

Baroreceptors are not as sensitive as osmoreceptors. You need about 15% decrease in ECV to get a 10-fold increase in ADH.

Question 7

What drives passive reabsorption of H2O in the proximal convoluted tubule?

Answer 7

Reabsorption of Na+ and glucose causes a change in osmolarity that makes H2O follow them

Question 8

Where in the nephron does H2O reabsorption not occur?

Answer 8

Ascending loop of Henle.

Question 9

Where does ADH have its greatest effect on reabsorption of H2O?

Answer 9

Collecting duct (can vary from 8-17%). Everywhere else in the nephron stays constant (PCT:67%, Descending Loop of Henle: 15%)

Question 10

What signaling cascade happens as a result of ADH biding to the V1 receptor on a light cell in the collecting duct?

Answer 10

G-protein activation of adenylyl cyclase -> increased cAMP levels -> activation of PKA -> phosphorylation of aquaporin II -> aquaporin II moves to the lumenal membrane of the light cell -> H2O can pass into aquaporin II, go through the cell and leave through aquaporin IV.

Question 11

How does the body know when to get rid of sodium?

Answer 11

It knows to get rid of sodium when the effective circulatory volume is high. This is sensed by the baroreceptors in the aortic arch and carotid sinus, the right atrium and juxtaglomerular apparatus in the kidney.

Question 12

How does sodium reabsorption progress as you move along the nephron?

Answer 12

*

Question 13

How is sodium reabsorbed in the proximal tubule?

Answer 13

Na-K ATPase pump maintains a low intracellular Na gradient. This allows for Na to flow down its gradient from the PCT lumen, through exchangers, into the cells and out the basement membrane.

Question 14

How is sodium reabsorbed in the thick ascending limb?

Answer 14

Na-K-2Cl Cotransport, K+ channel and Na/K ATPase.

Question 15

How is sodium reabsorbed in the distal convoluted tubule?

Answer 15

NaCl Cotransport and Na/K ATPase.

Question 16

How is sodium reabsorbed in the principal cell of the collecting duct?

Answer 16

Epithelial Na channel and Na/K ATPase.

Question 17

What four signal systems are responsible for control of sodium reabsorption in the kidney?

Answer 17

Direct hemodynamics, RAAS, Sympathetics, Natriuretics

Question 18

What mechanisms are responsible for the constant perfusion pressure in the glomerulus and thus constant GFR?

Answer 18

Myogenic and tubulo-glomerular.

Question 19

An isolated kidney is tested in an experiment on high blood pressure and urine production. The results are shown in the graph below. What accounts for this?

Answer 19

Increased BP increases the peritubular hydrostatic pressure. It also decreases the filtration fraction. This results in a decrease in oncotic pressure. With these two factors combined, you get “back leaking” of Na+ and water into the collecting duct and sent out as urine.

Question 20

How do cells in the kidney work to increase Na filtration in response to a decreased effective circulating volume?

Answer 20

Macula densa cells sense a decrease in filtered Na+. They signal to juxtaglomerular cells to secrete more renin. Renin is secreted. Angiotensin II is formed and stimulates the zona granulosa in the adrenal cortex to secrete aldosterone.

Question 21

How does aldosterone increase reabsorption of sodium in the kidney?

Answer 21

Aldosterone activates genes in the principal cells of the collecting ducts. Short term, these genes code for more Na+ channels. Long term they code of more Na/K ATPase pumps.

Question 22

How does the sympathetic nervous system play a role in Na+ reabsorption?

Answer 22

Decreased effective circulating volume causes baroreceptor-mediated signaling to the brain. The brain activates the sympathetic nervous system (the renal nerve specifically) to release renin from juxtaglomerular cells, vasoconstrict the afferent arteriole and increase PCT Na+ reabsorption.

Question 23

A patient comes to see you from the heart failure clinic. Blood tests reveal an elevated ANP. What does ANP do?

Answer 23

*

Question 24

What are the main controllers of short-term and long-term blood pressure values?

Answer 24

Short-term = Sympathetic Nervous System. Long-term = homeostatic control of Na and H2O by the kidney

Question 25

A 49 year old male comes to your clinic with essential hypertension. You prescribe him lisinopril and hydrochlorothiazide. Why this combination of drugs for this patient?

Answer 25

ACE-I prevents aldosterone-induced increased reabsorption of Na at the collecting ducts. HCTZ blocks Na reabsorption at the distal tubule. Both of these result in increased Na excretion, increased H2O excretion, reduced effective circulating volume and reduced BP.

Question 26

Where do the different diuretics act in the nephron?

Answer 26

Carbonic anhydrase inhibitors (inhibits Na-H exchanger in PCT), Loop diuretics (inhibits Na/K/2Cl exchanger in thick ascending loop of Henle), Thiazides (inhibits Na-Cl transport at distal tubule) and Amiloride (inhibits Na reabsorption at collecting duct principal cells)

Question 27

Why are heart failure patients so prone to developing edema?

Answer 27

Despite back up of blood, the body still senses a decreases effective circulating volume. Consequently RAAS and sympathetic tone are unregulated. Na and H2O are increasingly absorbed and you get fluid overload leading to edema.

Question 28

How does your body immediately respond when you eat three bananas in one sitting? How does it regain normal homeostasis?

Answer 28

If all of the K+ in the banana went into the blood you would become hyperkalemic and at risk for arrhythmias. Typically the body will secrete insulin and epinephrine (within minutes) to stimulated skeletal muscle uptake of K+ in the blood to keep levels consistent. For long-term regaining of homeostasis, aldosterone is secreted (within hours) and K+ is secreted into the collecting duct from the blood.

Question 29

How does K+ secretion occur?

Answer 29

Na/K ATPase pump is bringing K+ into the cell. The secretory K+ channel lets it pass into the collecting duct.

Question 30

What signal systems control K+ levels?

Answer 30

Serum [K+], aldosterone, tubular flow rate, ADH and acid-base.

Question 31

How does an increase in serum K+ alone cause increased secretion of K+ into the collecting duct?

Answer 31

Increased extracellular K+ levels stimulates the Na/K ATPase pump. More K+ is taken into the cell and more K+ goes out the secretory K+ channel into the collecting duct.

Question 32

How does aldosterone adjust the cell's ability to secrete K+?

Answer 32

Gene activation to increase # of K+ secretory channels and Na/K ATPase pumps.

Question 33

How does an increase in tubular flow rate cause increased K+ secretion?

Answer 33

As more K+ comes out, it is quickly whisked away into the urine, maintaining a high diffusion gradient from the cells to the collecting duct.

Question 34

How does the body separate the effects of aldosterone on Na+ and K+ in response to increased ECV?

Answer 34

Tubular flow rate & aldosterone balance each other out. An increased ECV causes decreased PCT reabsorption of K+, increased distal tubular flow and increased K+ secretion. At the same time, the increased ECV stimulates decreased aldosterone secretion and decreases the K+ secretory stimulation.

Question 35

How does the body separate the effects of aldsoterone on Na+ and K+ in response to decreased ECV?

Answer 35

Decreased ECV causes increased K+ reabsorption at the PCT. This causes a decrease in distal flow rate which will decrease K+ secretion. However, the decreased ECV will stimulate aldosterone release to secrete more sodium and potassium and the K+ effects will balance out.

Question 36

Why are patients with hyperaldosteronism at high risk for hypokalemia?

Answer 36

Increased aldosterone increases K+ secretory channels and K+ secretion. It also causes an increase in ECV, decreased PCT reabsorption, increased distal tubular flow and further increased K+ secretion.

Question 37

Why are patients on loop diuretics at risk for hypokalemia?

Answer 37

Blocking the Na/K/2Cl uptake channel in the thick ascending limb decreases Na reabsorption. This will increase the distal flow rate and increase K+ excretion. It will also cause a decrease in ECV which will cause an increase in aldosterone & an increase in K+ excretion. Finally, it will cause a decrease in loop K+ reabsorption, increased distal [K+] and increased K+ excretion.

Question 38

How does ADH promote K+ secretion and how do the effects of ADH help to maintain a constant K+ balance?

Answer 38

ADH stimulates increased K+ secretory channels and thus increased excretion. However, ADH also stimulates water reuptake via the aquaporin channels which decreases urinary flow rate and distal K+ secretion.

Question 39

How does the body increase or decrease K+ secretion in response alkalosis or acidosis?

Answer 39

Acidosis inhibits the Na/K ATPase pump and K+ secretory channel, increasing K+ retention. Alkalosis stimulates the Na/K ATPase pump and K+ secretory channel.

Question 40

How does the body recover from hypokalemia?

Answer 40

It shuts off all K+ secretory mechanisms. Max reabsorption of K+ is carried out in the collecting ducts by the intercalated (dark) cell's K+/H+ exchange channel.

Question 41

How does the parathyroid hormone reduce Ca excretion in response to low plasma Ca levels?

Answer 41

\*

Question 42

How much serum Ca2+ usually gets filtered by the glomerulus?

Answer 42

40%. The other 60% is bound to serum proteins.

Question 43

Where and how does most Ca2+ reabsorption take place in the nephron?

Answer 43

60% occurs at the PCT via passive paracellular transport

Question 44

How does PTH increase Ca2+ reabsorption?

Answer 44

Stimulation of active transcellular transport channels, ATPase pumps and Na/Ca2+ exchangers.

Question 45

How does PTH increase excretion of PO4-?

Answer 45

PO4- reabsorption is limited by its transport maximum. PTH blocks the Na/PO4 exchangers, lowering the transport maximum and increasing the amount of PO4 excreted in the urine.

Question 46

What percentage of serum magnesium is filtered by the glomerulus?

Answer 46

40%. The other 60% is bound to serum protein.

Question 47

Where is most magnesium reabsorbed?

Answer 47

70% is reabsorbed in the Loop of Henle and 25% in the PCT.