Normal Renal Physiology III

Question 1

How does LR fluid help maintain our blood pH?

Answer 1

LR contains lactate which gets converted to bicarb in the liver, maintaining acid-base balance

Question 2

Both LR and NS are electrically neutral. However, NS will make patients acidotic past ~2.5 L. Why?

Answer 2

Giving NS results in excess Na+ that the kidneys will excrete ; either Cl- or bicarb will follow, BUT Cl- is about 5x more numerous than HCO3- so body will more likely grab Cl- from the filtrate to pump back into the blood

This means that most of the negative electrolytes that remain in the urine will be bicarb resulting in metabolic alkalosis)

Question 3

Describe some traits about the cells at the proximal tubules.

Answer 3

Very thick

Lots of mitochondria (requires lots of ATP for the active pumps)

In other parts of the nephron, these cells are not as big since they act more as a passive filtration barrier

Question 4

Describe the anatomy and general function of the Loop of Henle.

Answer 4

The Loop of Henle dives down into the medulla of the kidney and is made up of the descending limb and ascending limb. Each limb has thin and thick portions.

In addition to reabsorbing more filtrate, it also sets up an electrolyte gradient.

Question 5

Describe the functionality and purpose of the thin and thick components of the limbs of the Loop of Henle.

Answer 5

The limbs of the Loop of Henle have thin and thick components.

Transporters in these membranes are different.

Thin component is primarily permeable to Na+ and H2O.

Thick component is impermeable to water and have Na+/K+/2Cl- pumps in them (cells are thicker to accommodate ATP requirement). Pump action of thick section = rate limiting step as to how quickly filtration can occur, and allows for ion concentration of blood beyond normal osmolarity.

Question 6

What happens at the thick portions of the limbs of the Loop of Henle if our ion load is too high (for example, after we eat a bunch of chips and drink a bunch of beer)?

Answer 6

If we have a huge ion load in the Loop of Henle, we can overpower the rate limiting steps of the ion pumps; ions will wash through without being reabsorbed into the blood (pumps cannot operate fast enough to save ions) and we end up losing electrolytes

Question 7

What is the purpose of the countercurrent exchange mechanism?

Answer 7

To concentrate urine multiple-fold

Question 8

Briefly describe how the countercurrent exchange mechanism works.

Answer 8

Sodium pumps pump Na+ into the tubules.

Water flowing in will enter the interstitial space due to higher concentration of Na+ there, leaving behind a more concentrated filtrate in the limbs.

Fluid in the medulla will then get more concentrated as more Na+ gets pumped out of the ascending limbs into the descending limbs…

The result is that the Na+ concentration in the descending limb keeps going up and water from the passing filtrate will follow concentration gradient into the interstitium - this allows us to concentrate our urine up to 1200 milli-osmoles

The non-parallel countercurrent set up of the limbs of the Loop of Henle allow the set up of this concentration gradient.

Question 9

At the Loop of Henle, how much more of the filtrate is reabsorbed?

Answer 9

About 20% (So at this point the filtrate is very concentrated, since 70% has been reabsorbed in the proximal tubule)

Question 10

What are the functions of the distal tubule?

Answer 10

• Loops back up to the glomerulus to sample afferent and efferent renal blood (macula densa output)
• Reabsorbs another 5% of filtrate (Na+)
  - Some of this is mediated by aldosterone in late distal tubule as it transitions into the collecting duct
• Reabsorption of Ca++ (dependent on PTH and Vit D)

Question 11

What are the functions of the collecting duct?

Answer 11

(Cortex)

• Aldosterone mediated reabsorption of Na+ (5-7% of filtrate)
• Small changes/fine-tuning of ion levels (K+, H+, HCO3-, Cl-)

(Medulla)

• More permeable to water: aldosterone-mediated water reabsorption
• H+ secretion

Question 12

What kinda of cells is the late distal tubule and collecting duct composed of?

Answer 12

Thick cells in the late tubule and collecting duct (further ion pumping and conservation of water via ADH stimulation)

Question 13

Describe the stages of renal excretion.

Answer 13

1. Filtration
2. Reabsorption
3. Secretion
4. Elimination

Question 14

Describe the secretion of drugs by the kidney.

Answer 14

Different parts of kidney have specific pumps that allows for secretion of substances into the urine

Most drugs that get renally cleared have moieties added to them by the liver which allows them to be secreted in the kidney into the filtrate

Question 15

Describe how creatinine is an indicator of kidney function.

Answer 15

Creatinine = product of protein breakdown (muscles); it is filtered into urine (no reabsorption or secretion). We measure how much of it is in our blood.

The amount of creatinine that is filtered into the urine is a direct representation of how much blood is filtered by the kidneys

-If creat is high in BLOOD, that means kidney is not doing a good job clearing it 

It is normally analyzed as a value that occurs over a day (a 24 hr total of creat filtration; analyze creat in 24 hrs of urine vs creat in blood) but can also be analyzed as a value that occurs over 2 hours

Question 16

What is the normal creatinine lab value?

Source of variabilities?

Answer 16

**Normal lab range: <1.2-1.4

Creat level in urine is normally 100- when it gets down to 10-15, pt needs dialysis

-Variability: pt may not have as much muscle mass so creat may be low (frail elderly pts)

For example if you have a really frail pt, their expected creat may be 0.6 so 1.1 may be high even though it is usually acceptable for normal pt

Question 17

What is BUN? What is it dependent on and how can we use it in conjunction with Creat?

Answer 17

BUN (blood urea nitrogen) = ultimately dependent on volume status, not just renal clearance (much more variability than creat so not as good of an assessment tool of renal function than creat levels)

-Therefore we look at Creat/BUN ratio; if its greater than 20:1, than we worry about dehydration of pt

Question 18

How does the kidney regulate body pH?

Answer 18

• Bicarb concentration control (primary)

- Protein secretion and H+ transport (secondary)

Question 19

What is renal tubular acidosis?

Answer 19

A condition where bicarb transporters in kidneys don’t function well so pt is in constant metabolic acidosis

Question 20

What is the relevant equation for pH regulation in the kidney?

Answer 20

H+ + HCO3- H2CO3

Enzyme: carbonic anhydrase

Question 21

What chemical reaction occurs in the kidneys during metabolic acidosis?

Answer 21

Carbonic anhydrase breaks H2CO3 down into H+ and HCO3-

Na+ is antiported with H+; H+ gets transported out into urine as Na+ gets transported into blood.

H+ in urine is locked to a buffer such as phosphate and excreted

Bicarb will be retained in the blood to help compensate
for the metabolic acidosis and this whole cycle repeats until compensation is complete

Ammonia ions can bind to H+ as well (Ammonia is directly excreted by the kidneys, so it just takes a proton with it if there is a proton excess in the system)

Question 22

Describe what happens when your macula densa detects low MAP.

Answer 22

Low Map –> Low GFR –> proportionally more filtrate reabsorbed at the distal tubule: results in a low amount of NaCl here –> macula densa senses this low NaCl

In response, it:

• Stimulates vasodilation of local afferent artery and vasoconstriction if no hypovolemia
• Stimulates renin release leading to vasoconstriction of local efferent arteries
• Stimulates increased reabsorption of Na and Cl in the proximal tubule

Question 23

Describe how the Renin-Angiotensin-Aldosterone system works.

Answer 23

Renin (released by macula densa) converts angiotensinogen (circulating throughout our blood) to angiotensin I.

Angiotensin I gets converted to Angiotensin II by endothelial cells and ACE in our lungs.

Angiotensin II stimulates aldosterone secretion from the adrenal gland

        -Aldosterone increases preload and increase afterload, promotes RBF and increases water retention

Question 24

Four main functions of the kidneys:

Answer 24

Glucose metabolism (insulin excretion)

RAA-axis

Calcium regulation

RBC generation process (erythropoieten production)

Question 25

Describe calcium regulation by the kidneys

Answer 25

Ca++ plasma levels fall —> PTH increases –>

1. Release of Ca++ from bones
2. Increase in vit-D dependent absorption of Ca++ from GI
3. Increased reabsorption of Ca++ from kidneys

Question 26

What are the effects on Ca++ when PTH is low?

Answer 26

Low PTH = Ca++ wasted in urine

When excreted Ca++ is too high, it can precipitate into kidney stones.

Question 27

Why can renal failure patients be chronically anemic

Answer 27

Kidneys release erythropoeiten which goes to the bone marrow to produce RBCs.

>>Often renal failure pts are chronically anemic due to the lack of this release!

Question 28

What are the effects of some of our anesthesia on renal function?

Answer 28

Fluoride moeities in volatile anesthetics accumulate when gas are run at low flows**

-High levels of fluoride ions can be toxic to the kidneys 

Propofol and thiopental have also been implicated as nephrotoxic at very high doses

Question 29

Why do we administer acetylcysteine to renal patients underdoing IV dyes for angiography?

Answer 29

IV dyes can be very caustic to the kidneys.

N-acetylcysteine - free radical binder that may have protective effect on kidneys especially in the presence of IV dyes

Renal pts that are undergoing IV dyes for angiography are often given fluids, mannitol, and acetylcysteine to try to wash out this IV dye as fast as possible

Question 30

How do diuretics work?

Answer 30

They decrease reabsorption of Na+ and H2O

They increase RBF at the cost of electrolyte imbalance and potential dehydration

Question 31

What can happen if you correct hyponatremia too quickly?

Answer 31

Central Ponteine Myolinolysis

Ponteines cells of pons in the brain stems get their myeline stripped off

-"Locked in syndrome": cortex working fine, but no transmission is escaping their brain stem; completely aware but cannot communicate with their bodies, so DO NOT correct hyponatremia too rapidly!

Question 32

How do loop diuretics work?

Answer 32

Interferes with ion transporter pump in the ascending thick limb of the Loop of Henle

Question 33

What are side effects of loop diuretics?

Answer 33

Electrolyte disturbances since it interferes with ion reabsorption

Question 34

What are loop diuretics used to treat?

Answer 34

CHF, hypertension, oliguria, hypercalcemia

Question 35

How do thiazides work? What are they used to treat?

Answer 35

Increase Na+ excretion at the distal tubule + carbonic anhydrase activity at the proximal tubule

Used to treat CHF, hypertension and hypercalcemia

Question 36

How do K+ sparing diuretics work and what condition is required for them to do so?

Answer 36

They are aldosterone antagonists that work only if aldosterone levels are high.

Question 37

In what patient population should you avoid K+ sparing diuretics?

Answer 37

CHF and liver failure pts

Question 38

What are carbonic anhydrase inhibitors used for?

Answer 38

Commonly used in eyedrops and for ppl w glaucoma as PO med

Question 39

How do carbonic anhydrase inhibitors work?

Answer 39

Affects Na+ and H+ proximal tubule reabsorption which results in bicarb wasting (urine alkalization)

Decreases intraocular pressure and bicarb