Test 2 (Mechanisms to Adjust Urine Concentration)

Question 1

Renal Control of Salt and Water Balance

Answer 1

Crucial for regulation of:
- Blood Pressure

• Extracellular Fluid Solute Concentration
• Concentrations of Na+, K+ in Body Fluids

Normal function of these mechanisms allows:
- Water retention doing Dehydration

• Excretion of Dilute Urine when well Hydrated
• Sodium EXCRETION when Blood Pressure rises
• Sodium RETENTION when Blood Pressure falls

Question 2

Failure of Renal Control of Salt and Water Balance can cause:

Answer 2

• Edema
• Disorders of plasma K+ Concentration: HYPERkalemia, HYPOKalemia
• Undesirable changes in Blood Pressure
• Acid/Base disorders
• Neurological Problems: Shrinking or Swelling of the Brain

Question 3

Sodium Reabsorption Mechanisms

Answer 3

1) Proximal Tubule (50-55%):
- Cotransport with Glucose, Amino ACIDS, Phosphate

• Countertransport with H+ (Na+/ H+ Exchange)

2) Thick Ascending Limb (30-45%):
- Na+, J+, 2Cl- Cotransport

3) Early Distal Convoluted Tubule (5-8%):
- Na+, Cl- Cotransport

4) Late Distal Convoluted Tubule, Collecting Duct (2-3%):
- Luminal Na+ Membrane Channels

Question 4

Water and Chloride follow Sodium

Answer 4

1) WATER REABSORPTION:
- Always PASSIVE; can be Transcellular or Paracellular

• Follows Osmotic Gradients established by Reabsorption of Sodium, other solutes

2) CHLORIDE REABSORPTION:
- Always linked, either directly or indirectly, to Na+ Reabsorption (Cl- can balance the + Charges)

• Specific Mechanisms differ in different segments

Question 5

Loop of Henle

Answer 5

1) DESCENDING LIMB:
- Freely PERMEABLE to WATER

• IMPERMEABLE to Na+, Cl-

2) ASCENDING LIMB:
- Always IMPERMEABLE to WATER

• THIN Segment: NaCl Reabsorption mechanism is Controversial
• THICK Segment: Active Na+, K+, 2Cl- Cotransport (Has K+ Leak Channels that allows K+ to follow its Concentration Gradient. This established the Positive Tubular Potential)

Question 6

Late DCT and Collecting Duct

Answer 6

* THE MAJOR SITE OF PHYSIOLOGICAL CONTROL OF SALT AND WATER BALANCE!!!!!!!***

1) ALDOSTERONE: Stimulate Na+ Reabsorption, K+ Secretion, H+ Secretion in this Segment
2) ATRIAL NATRIURETIC PEPTIDE: Inhibits Na+ Reabsorption (Medullary Collecting Duct)
3) ANTIDIURETIC HORMONE aka ARGININE VASOPRESIN (AVP) Stimulates Water REABSORPTION

Question 7

Cation Transport in Late Distal Tubule, Collecting Duct

Answer 7

• Not the Large TRANSEPITHELIAL POTENTIAL (50mV, Lumen NEGATIVE)
• This is part of the DRIVING FORCE of K+ and H+ Secretion by the PRINCIPAL CELLS!!!!!!!!

Question 8

Aldosterone Mechanisms for Increasing Na+ Reabsorption in PRINCIPAL CELLS

Answer 8

1) Incorporation fo Na+ Channels in Luminal Membrane

2) Incorporation of Na+, K+, ATPase Ion pumps in Basolateral Membrane

Question 9

Water Permeability of Collecting Duct is Physiologically Controlled

Answer 9

1) Well Hydrated Individuals:
- Collecting Duct is IMPERMEABLE TO WATER

• Water remains in Tubular Lumen; Dilute Urine is Excreted

2) DEHYDRATED INDIVIDUALS:
- Collectign Duct is HIGHTLY WATER-PERMEABLE

• Water is Reabsorbed; Low Volume of Concentrated Urine is Excreted

Question 10

ADH (AVP) on Late Distal Tubule and Collecting Duct

Answer 10

• ADH (AVP) INCREASES H2O Permeability (Reabsorption) of Late Distal Tubule, Collecting Duct via V2 RECEPTORS and Insertion of Aquaporin Channels!!!!!!!!!!!

Question 11

Solute Concentrations in Particular Interstitium

Answer 11

• INNER MEDULLARY INTERSTITIAL FLUID has a Very High Solute Concentration

Question 12

Countercurrent Multiplies Mechanism

Answer 12

• Concentrates Solute in Medullary Interstitial
• High Solute Concentration enables kidneys to Excrete Highly Concentrated Urine, conserve Water during periods of Dehydration

This Mechanisms requires Integrated Function of 3 Components:
1) Descending, Ascending Limbs of Henle’s Loop

2) Vasa Recta Capillaries
3) Collecting Ducts

Question 13

Components of Countercurrent Multiplier

Answer 13

1) Na Gradient that the Na, K, Clo Cotransporter can establish in TAL is 200 mOsm/ Kg
2) Interstitial becomes HYPEROSMOLAR and pulls WATER OUT of the Descending Limb
3) Urine in Descending Limb is CONCENTRATED
4) Process Repeats
5) Augmented by action of ADH in CD

Question 14

Recycling Concentrated UREA in Inner Medulla

Answer 14

• AVP promotes UREA Reabsorption from Inner Medullary Collecting Duct

Question 15

Role of Urea in the Countercurrent Mechanism

Answer 15

• In the presence of ADH, Water but nor UREA is Reabsorbed in the Cortical Collecting Tubule, resulting in an INCREASE in the Tubular Fluid UREA Concentration
• In the Presence of ADH, more Water but NOT UREA is Reabsorbed in the Medullary Collecting Tubule, further raising the Tubular Fluid Urea Concentration. The Inner Medullary Collecting Tubule is relatively PERMEABLE to UREA; as a result, Urea passively diffuses into the Interstitial, INCREASING the Interstitial Osmolarity

Question 16

Vasa Rects

Answer 16

VASA RECTA maintain SOLUTE GRADIENT

• Water and NaCl are EXCHANGED between Descending and Ascending Limbs
• Solute gradient is maintained while SMALL amounts of NaCl and Water are RETURNED to SYSTEMIC CIRCULATION

**IF the Blood Flow INCREASES, there will be a Concentration Gradient that will make out more Solutes and abolish the Concentration Gradient and not allow us to Concentrate our Urine

Question 17

Antidiuresis

Answer 17

• HIGH AVP
• AVP makes the Collecting Duct Epithelium HIGHLY WATER PERMEABLE.
• Water is Reabsorbed in this Segment as a LOW VOLUME, HIGHLY CONCENTRATED URINE is Excreted

Question 18

Flows, Solute Concentrations in Antidiuresis

Answer 18

NOTE: The Vasa Recta remove more Water and Solute from the MEDULLA than they bring in

Question 19

Diuresis

Answer 19

• LOW AVP
• Here, a HIGH Volume of DILUTE URINE is Excreted
• Collecting Duct Epithelium is IMPERMEABLE to WATER
• Note the LOWER SOLUTE Concentrations in the MEDULLARY INTERSTITIUM!!!!!!!!!!!!!!

Question 20

Summary of NaCL and H2O Transport throughout the Nephron during an Antidiuresis and a Water Diuresis

Answer 20

• The tubular Fluid and Interstitial Concentrations are expressed in milliosmoles per Kilogram (mOsm/Kg)
• Note that the Composition and Volume of the Tubular Fluid are essentially the same at the end of the Loop of Henle as the Excretion of a Concentrated or Dilute Urine is determined primarily in the Collecting Tubules

Question 21

Obligatory Urine Volume (WATER LOSS)

What is minimum Daily Required to Eliminate Wastes?

Answer 21

• Body generates 600 Milliosmol of Waste/Day
• Maximum Urine Concentration = 1200 mOsm/ L

(600 mOsm/day)/ (1200 mOsm/L) = 0.5 L/day

What if the Kidneys couldn’t concentrate Urine above Plasma Solute Concentration?

(600 mOsm/ Day)/ (300 mOsm/ L) = 2.0 L/ day

Question 22

Osmolar Clearance

Answer 22

Osmolar Clearance (Cosm) = Uosm x V/ Posm

***When Kidneys EXCRETE Excess Solute = Cosm INCREASES!!!!!!!!!!

**When Solute is RETAINED = Cosm Falls!!!!!!!!!

Question 23

Free Water Clearance (CH2O)

Answer 23

DEFINITION: EXCRETION of Water in Excess of amount needed to Excrete Ososmotic Urine

• Ex: Excretion fo Sulte Free Water by the Kidneys

CH2O = V- Cosm

1) If Uosm Posm CH2O is NEGATIVE!!!!!
- Pure Water is RETAINED

Question 24

Fractional Excretion

Answer 24

DEFINITION: The fraction (percentage) of the filtered load of a Substance that is Excreted in Urine

Fex = (Amt Excreted)/ (Amt Filtered) ——–>

            = (Ux  x  V)/ (Px  x GFR)

• If CREATININE Clearance = GFR

Fex = (Ux x V)/ (Px x [(Ucr x V)/ Pcr]) ———–>

           = (Ux  x Pcr)/ (Px  x Ucr)

Question 25

Fraction Excretion Example

Answer 25

Ex: In a Spot Urine Sample, Fractional Excretion fo Na (FE Na) = (UNa x Pcr)/ (PNa x Ucr) x 100

***BELOW 1% = PRERENAL and AGN —> Na AVIDLY REABSORBED!!!!!!!!!!

***GREATRE Than 2% = ATN, RENAL!!!!!!!!!!