Lecture 2: Nephron physiology

Question 1

What is the role of the glomerulus (Bowman’s Capsule)?

Answer 1

To for an ultra-filtrate of plasma

Question 2

What are 2 features of the glomerular filtration barrier? AKA the basement membrane

Answer 2

1. Charge selective: basement membrane is negatively charged due to glycoproteins which compose it. Negatively charged proteins are thus repelled and are not able to pass through.
2. Size selective: molecules greater than 50-100 angstroms will not pass through

Question 3

Glomerular Filtrate Rate (GFR)=

Answer 3

rate of volume which leaves the capillaries and enters the bowman’s space. Expressed in mL/Min

Question 4

What is considered a normal GFR?

Answer 4

125mL/Min

180 Liters/Day

Question 5

Renal blood flow is ___% of cardiac output?

Answer 5

20%; or 1200ml/min

Of all organs, only the liver gets a higher % of cardiac output.

Question 6

Only about ___% of what is filtered through the Bowman’s capsule becomes urine.

Answer 6

1%

Question 7

What 4 factors determine GFR?

Answer 7

1. THE ULTRAFILTRATION COEFFIENT: this depends on capillary permeability and surface area available for filtration
2. ONCOTIC PRESSURE: since there should be no free protein in the Bowman’s space, the net direction of this force should oppose filtration.
3. NET HYDRAULIC PRESSURE: drives fluid from capillaries into Bowman’s space.
4. CAPILLARY PLASMA FLOW RATE: higher flow = greater filtration.

Question 8

What is the Net Filtration pressure?

Answer 8

Calculated by:

Glomerular hydrostatic pressure (60mmHg) - Bowman’s capsule pressure (18mmHg) - Glomerular oncotic pressure (32mmHg)

= 10mmHg Net Filtration pressure

Question 9

How does the body get back filtered plasma?

Answer 9

As plasma moves toward the end of the glomerular capillary, filtration slows due to an Increase in oncotic pressure (as fluid is removed the protein concentration increases)

Capillary Hydrostatic Pressure drops significantly at the level of the efferent arteriole resulting in maximal reabsorption into the vasa recta and peritubular plexi

Question 10

Autoregulation refers to the kidney’s ability to regulate GFR over a range of conditions. At what range of MAP will GFR and renal blood flow remain constant?

Answer 10

a MAP range of 80-200 mmHg (some sources are around 55-180 mmHg)

Question 11

The Macula Densa monitors what?

Answer 11

It monitors Na levels in the Afferent vs Efferent arterioles around the glumerulus.

Question 12

What 2 mechanisms assist with auto regulation of GFR?

Answer 12

1. constriction and dilation of pre capillary sphincters in the afferent and efferent arterioles.
2. INCREASED Na delivery to the macula dense will DECREASE GFR.

Question 13

What is the concept of renal clearance?

Answer 13

the volume of plasma from which all of a given substance is removed per unit of time in 1 pass through the kidney.

Question 14

If a substance is neither secreted nor reabsorbed then it’s clearance is = to ?

Answer 14

GFR (example: insulin)

Question 15

If a substance is completely reabsorbed, then clearance is = to ?

Answer 15

clearance is 0.

Example: glucose, under normal circumstances

Question 16

If clearance is > GFR then ___?

Answer 16

There must be net secretion.

Question 17

If clearance is < GFR then ___?

Answer 17

There must be net reabsorption.

Question 18

If clearance is = to GFR then ___?

Answer 18

There is neither net reabsorption or net secretion.

Question 19

Renal clearance of creatinine is used clinically to estimate GFR. What is the best test to evaluate creatinine clearance and therefore GFR?

Answer 19

24-hour urine collection/test.

Question 20

What is creatinine?

Answer 20

Creatinine is a normal component of blood, a byproduct of skeletal muscle protein breakdown.

Question 21

Normal renal function corresponds to ___% of functioning nephrons and a GFR of ___.

Answer 21

100% and a GFR of 125ml/min

Question 22

Reduced renal function corresponds to ___% of functioning nephrons and a GFR of ___.

Answer 22

10-40% and a GFR of 12-80ml/min

Question 23

Renal failure corresponds to ___% of functioning nephrons and a GFR of ___>

Answer 23

<10% and a GFR of <12

Question 24

List the nephron structures/regions from proximal to distal.

Answer 24

Glumerulus
Bowman's capsule
Proximal tubule
Loop of Henle
Distal convoluted tubule
collecting ducts

Question 25

What area of the nephron is the main reabsorptive area?

Answer 25

Proximal Tubule

Question 26

Reabsorption in the proximal tubule is Hypo- Iso- or Hyper-osmotic?

Answer 26

Iso-osmotic

Question 27

What is secreted by the proximal tubule?

Answer 27

• Organic acids via anion pumps (diuretics, antibiotics)
• Organic bases
• Ammonia (important for acid-base balance)

Question 28

What is reabsorbed by the proximal tubule?

Answer 28

• Na, Cl, and water
• HCO3 reabsorption via carbonic anhydrase
• Vitamin ___ and K

Question 29

What are some characteristics of the fluid leaving the proximal tubule.

Answer 29

• osmolality is = to plasma
• Tubular flow is 1/3 GFR
• Glucose, protein and amino acids are absent (in a healthy individual, glucose should be reabsorbed, amino acids and protein should not filter through the glumerulus.
• Increased Cl- concentration complared to plasma. More stays behind to maintain electroneutrality d/t more HCO3- is being reabsorbed back into the capillaries.

Question 30

What are the 3 functional segments of the Loop of Henle?

Answer 30

1. DESCENDING THIN SEGMENT
2. ASCENDING THIN SEGMENT
3. THICK ASCENDING (MOST IMPORTANT)

Question 31

Describe the functions/characteristics of the Descending Thin Segment of the Loop of Henle.

Answer 31

• Highly permeable to to most solutes
• Permits simple diffusion of substances through its walls.
• 20% of filtered water is reabsorbed in this segment.

Question 32

Describe the functions/characteristics of the Ascending Thin Segment of the Loop of Henle.

Answer 32

• virtually impermeable to diffusion of water

- Reabsorption of capacity for ions such as Ca, HCO3, and Mg.

Question 33

Describe the functions/characteristics of the Thick Ascending Segment of the Loop of Henle. (most important)

Answer 33

• Considered the “diluting segment of the nephron”
• Key feature: it is IMPERMEABLE TO WATER while solute is pumped of the tubular fluid.
• the luminal membrane has a 1Na, 1K, 2Cl transporter pump (this is the TARGET SITE OF LASIX and the ONLY segment where Cl is ACTIVELY transported.
• The intraluminal charge is + in the TAL, this drives further reabsorption of Mg2+ and Ca2+.

Question 34

The Distal Tubule contains some special cells called the ___. What is the purpose of these cells?

Answer 34

The Macula Densa.

The Macula Densa senses Na concentration in the distal tubule compared to the Efferent/Afferent arterioles (blood stream).

If the macula densa senses high Na, the GFR will decrease. (provides feedback control)

Question 35

Describe the functions/characteristics of the Distal Tubule.

Answer 35

• similar reabsorptive characteristics as the thick segment of ascending limb.
• Virtually impermeable to water
• Tubular fluid becomes more dilute as solutes are reabsorbed.

Question 36

Water permeability is controlled by the presence or absence of what substance?

Where is this substance active?

Answer 36

Anti-Diuretic Hormone (ADH)

ADH is active in the Later distal tubule.

Question 37

What happens in the absence of ADH?

Answer 37

• Tubular cells virtually impermeable to water. Water is not reabsorbed and it is lost through urine.
• Alcohol blocks ADH. Drunk people have to pee often and have very dilute urine.

Question 38

What happens in the presence of ADH?

Answer 38

High levels of ADH make the tubular segment permeable to water. (Water can be reabsorbed)

Question 39

Reabsorption of sodium and secretion of potassium is controlled by what and where?

Answer 39

Aldosterone controls the rate at which Na is reabsorbed and K is secreted.

Aldosterone is active in the Distal Tubule

Secretion of H+ by hydrogen-ATPase against a large concentration gradient takes place. (1000 : 1)

Question 40

Hydrogen and Potassium are regulated by 2 distinct cells:

Answer 40

1. Principal cells

2. Intercalated cells

Question 41

What is the function of Principle cells?

Answer 41

reabsorbed sodium and water from the lumen and secrete potassium into the lumen.

Question 42

What is the function of Intercalated cells?

Answer 42

reabsorption of bicarbonate and potassium ions and secrete Hydrogen into the lumen.

(important for acid/base regulation.)

Question 43

The medullary collecting duct reabsorbes < ___% of water and sodium.

Answer 43

10%

permeability to water is controlled by the level of ADH

The medullary collecting duct is permeable to urea. reabsorption of urea into the interstitial aroudn the collecting duct increases the osmolality of medulla, and contibutes to form concentrated urine.