Ch. 17 Day 2

Question 1

Clearance

Answer 1

Net amount that is lost/excreted

Volume of plasma from which a given substance is cleared by the kidneys per unit time

Every substance in the blood has own distinct clearance values; units expressed as volume of plasma per unit time, e.g. mL/min or L/day

Question 2

Clearance Equation (**KNOW FOR EXAM)

Answer 2

((mass of x in urine) * ( urine volume/time))/plasma concentration of x

Ex: (18.2mg/mL)(1 mL/min)/0.26 mg/mL = 70 mL/min

Know how to work this equation…and know units

Question 3

The concept of clearance can be used to calculate GFR, assuming you use a substance that is?

Answer 3

1. Freely filterable at the glomerulus (so that its concentration in glomerular filtrate is the same as in plasma)
2. Not secreted by tubules
3. Not reabsorbed by tubules

Such a substance is the polysaccharide INULIN
–do NOT confuse that with insulin

Question 4

Use of clearance of inulin to calculate GFR

Answer 4

If mass excreted/time = mass filtered/time, then:

GFR = C(inulin) = (U(inulin))(V)/P(inulin)

1. Infuse in inulin into a subject such that its plasma concentration is 4 mg/mL
2. Collect using for 2 hours, collected 0.2L
3. Measure urine inulin concentration: 360 mg/mL

What is GFR?

(360 mg/mL)(0.2L/0.2 h)/4 mg/L = 18L/2h = 9L/h = 150 mL/min

Question 5

If inulin were secreted, would the calculated GFR be higher or lower than the true GFR? Why?

Answer 5

Higher b/c it’s secretion

If inulin were absorbed, GFR would be lower

Question 6

Glucose is freely filtered at the glomerulus, but it is also totally reabsorbed in the proximal tubules and returned to plasma. What is the clearance of glucose?

Answer 6

Zero return on glucose, because it’s returned to plasma

Question 7

Reabsorption

Answer 7

Recall that GFR = 180L/day and total body water = 40L. Thus almost all of that 180L (99%) must be returned to circulation via reabsorption in tubular epithelium
–filtration is nonselective (except for protein); reabsorption is highly selective

Question 8

What is reabsorbed?

Answer 8

Water
Electrolytes (ions) - Na+, K+, Cl-, HCO3-, H+, Ca2+, PO4(^3)-
Small organic molecules - glucose, AAs, etc.

Question 9

Is water reabsorbed via active transport or passively?

Answer 9

Passively!!

Water is always reabsorbed passively (by osmosis), there is NOT ACTIVE TRANSPORT OF WATER

Question 10

General pathway for reabsorption

Answer 10

Tubule –> epithelial cells –> interstitial –> peritubular capillaries

Question 11

When it comes to the following substances, which one is incompletely reabsorbed? Why?

water
sodium
glucose
urea

Answer 11

Urea is incompletely reabsorbed, so we tend to lose it from the body.

It’s how the body disposes/excretes excess nitrogen

Question 12

When it comes to the following substances, which one(s) are highly reabsorbed (99% and up reabsorption rate)?

water
sodium
glucose
urea

Answer 12

Water (99%), sodium (99.5%), glucose (1005)

Question 13

Tubular reabsorption of some substances cannot be physiologically controlled.

Answer 13

Ex: glucose filtered = 180g/day, glucose excreted = 0g/day

Tubular capacity for reabsorption of glucose > GFR, so reabsorption of glucose is always maximal

Therefore, reabsorption of glucose is NOT adjusted or altered

Question 14

Reabsorption of H2O and Na+ can be altered under normal conditions

Answer 14

Ex: ingested water will be excreted into urine w/in a few hours

Therefore, there is a control mechanism which acts to maintain plasma water w/in fairly narrow limits

Question 15

What are the methods of reabsorption?

Answer 15

Epithelial transport (transcellular transport)

Paracellular transport

Question 16

Epithelial transport (transcellular transport)

Answer 16

Substances cross apical and basolateral membranes of tubule epithelial cells

Apical side faces fluid

Question 17

Paracellular pathway

Answer 17

Substances pass through the cell-cell junction between 2 adjacent cells
–includes small anions, water…

Question 18

Is there low or high hydrostatic pressure in peritubular capillaries? What does this favor?

Answer 18

Lower hydrostatic pressure in peritubular capillaries

Favors the movement of fluid and solutes into those capillaries instead of out of them

Question 19

In general, whatever happens to Na+ will also happen to ____.

Answer 19

Water

Question 20

Reabsorption: Na+ Cotransport

Answer 20

aka Secondary Transport

Carrier SGLT1 will not bring Na+ in unless it’s also bringing in a glucose (and vice versa); this allows both of these things to be reabsorbed

Question 21

Reabsorption of Glucose

Answer 21

Glucose/Na+ cotransporters have a transport maximum (Tm)

• -a) if there is too much glucose in filtrate, it won’t be completely reabsorbed b/c all carriers are in use (saturated)
• -b) extra glucose spills over into urine = glycosuria and is a sign of diabetes mellitus
• -c) extra glucose in the blood also results in decreased water reabsorption and possible dehydration

Question 22

In the Proximal Tubule, what percentage of water and Na+ is filtered?

Answer 22

65%

Question 23

Descending limb is highly permeable to ____, and somewhat permeable to?

Answer 23

Highly permeable to water

Somewhat permeable to ions, Na+, and urea

Question 24

Thick ascending limb is impermeable to ____, which is important for?

Answer 24

Impermeable to water, important for kidney ability to concentrate urine

Question 25

In the collecting duct, the ability to reabsorb ____ is possible, but completely dependent on?

Answer 25

Ability to reabsorb water is possible, but completely dependent on hormone control (ADH, aldosterone)

Question 26

Summary of tubular transport

Answer 26

1. Water transport entirely via PASSIVE DIFFUSION 2. As progress through tubular system, volume of tubular fluid decreases due to reabsorption of water - -progressively concentrating the urine 3. Avid reabsorption of substances of nutritional significance (glucose, AA, etc.) takes place via secondary active transport in proximal tubules 4. Reabsorption of metabolic wastes (urea, creatinine) poor or nonexistent 5. Reabsorption of electrolytes (sodium, potassium) by tubules is under physiological control and can be altered under different conditions

Question 27

Kidneys control osmolality

Answer 27

Osmolality = solute concentration Kidneys control osmolality of body fluids by excreting either a concentrated (greater proportion of solutes) or dilute (greater proportion of water) urine

Question 28

The major determinant of plasma osmolality is ____.

Answer 28

Na+ Therefore (Osm)plasma is a function of [Na+]plasma When (Na+)plasma increases, (Osm)plasma increases

Question 29

Increase in (Osm)plasma

Answer 29

Kidney conserves water (reabsorbs more water than solutes) --> restores (Osm)plasma

Question 30

Decrease in (Osm)plasma

Answer 30

Kidney excretes water (reabsorbs more solutes than water) --> restores (Osm)plasma

Question 31

Collecting Duct and ADH

Answer 31

1. Last stop in urine formation 2. Impermeable to NaCl but permeable to water - -a) also influenced by hypertonicity of interstitial space - water will leave via osmosis if able to - -b) permeability to water depends on the number of aquaporin channels in the cells of the collecting duct - -c) availability of aquaporins determined by ADH 3. ADH binds to receptors on collecting duct cell s--> cAMP --> protein kinase --> vesicles w/ aquaporin channels fuse to plasma membrane (water channels removed w/o ADH) 4. ADH produced by neurons in hypothalamus but stored and released from posterior pituitary gland - release stimulated by increase in plasma osmolality

Question 32

Excreting Concentrated Urine

Answer 32

increase in (Osm)plasma --> osmoreceptors send nerve signals --> posterior pituitary secretes ADH --> medullary collecting duct --> insertion of aquaporin into epithelium --> increased water reabsorption --> concentrated urine (conserves water)

Question 33

Excreting Dilute Urine

Answer 33

decrease in (Osm)plasma --> osmoreceptors (NO nerve signal) --> posterior pituitary (NO ADH release) --> medullary collecting duct --> NO insertion of water pores into aquaporin --> decreased water reabsorption --> dilute urine (excretes water)

Question 34

Summary of Effects of ADH on Urinary Excretion

Answer 34

Increase in ADH --> water reabsorbed --> concentrated urine Decrease in ADH --> water excreted --> dilute urine Excretion of concentrated urine is a major determinant of an organism's ability to survive in a terrestrial environment Human kidney can produce a maximal urinary concentration of 1200-1400 most/kg, 4-5 times higher than plasma osmolality (300 most/kg)

Question 35

Urinary concentration takes place as fluid moves through ____ ____.

Answer 35

Collecting duct Medullary interstitial fluid around collecting ducts is hyperosmotic Therefore, when ADH increases, water diffuses out of ducts

Question 36

Countercurrent multiplier and exchange system

Answer 36

Sets up and maintains high medullary interstitial osmolality Present in 30-40% of nephrons whose loops are long, extending into inner medulla. Glomeruli for these nephrons are in juxtamedullary area and mid cortex

Question 37

What's a countercurrent system?

Answer 37

fluid flowing in opposite directions in adjacent tubules Anatomy of tubules and blood vessels in MEDULLA fit this definition

Question 38

Countercurrent Multiplication

Answer 38

Most important element is active pumping of sodium ions from ascending limb of Henle's loop into medullary interstitial Movement of water in response to increasing interstitial osmolality is passive; at any given level of the loop, acts to equilibrate osmolalities between interstitial and descending limb New fluid is constantly entering; as it moves down loop, its osmolality increases Final result: although the gradient across the loop is never more than 200 mOsm/kg, a large gradient (900-1100 most/kg) exists from top to bottom Thus, in the presence of ADH, water in the collecting duct readily diffuses into hyperosmotic intersitium

Question 39

When water diffuses into interstitium, why doesn't this dilute the interstitium, thus destroying the gradient?

Answer 39

B/c of Vasa Recta

Question 40

Vasa Recta

Answer 40

System of passive exchange capillaries closely associated w/ Henle's Loop Solutes diffuse in, water comes out - as blood descends, it encounters high medullary interstitial solute concentrate As blood leaves, its (Osm) only slightly higher than when it entered and only small amounts of solutes and carried away from medulla - Descending limb: solutes (Na+) diffuse in, water diffuses out, blood becomes hyperosmotic - Ascending limb: solutes diffuse out, water diffuses in, blood approaches isosmotic