Module 4: Renal II

Question 1

Micturition reflex

1. What is it?
2. What volume does it kick in?
3. What volume is its maximum (then what happens)?
4. How much is left once micturition is completed?

Answer 1

1. The urge to urinate.
2. Around 200 mL.
3. 500 mL, the internal sphincter is forced open, leading to opening of the external sphincter and loss of voluntary opposition
4. 10 mL.

Question 2

What are the 3 important structures of micturition?

Answer 2

1. Detrusor muscle: makes up majority of the bladder wall
2. Internal sphincter: smooth muscle, passively contracted
3. External sphincter: skeletal muscle, stays contracted

Question 3

Define incontinence. Give 5 causes.

Answer 3

The inability to control urination voluntarily.

1. Infants: corticospinal connections yet to be established
2. Damage to internal or external sphincter
3. Spinal cord damage
4. Aging
5. Prostate growth

Question 4

What four parameters are balanced by homeostatic mechanisms for fluid and electrolyte balance?

Answer 4

1. Fluid volume: dictates blood volume, dictates blood pressure
2. Osmolarity: dictates cell volume
3. pH: protein folding and optimization
4. Concentrations of individual ions: Na⁺, K⁺, Ca²⁺

Question 5

Mass balance: what are the three methods remove excess fluid and molecules from the body?

Answer 5

1. Kidneys
2. Feces and sweat
3. Lungs: lose water and help remove H+ and HCO₃ by excreting CO₂

Question 6

What cell in the kidney is important for maintaining cell volume and osmolarity? How does it do this?

Answer 6

Renal tubule cells (Loop of Henle in juxtamedullary nephrons) are constantly exposed to hypertonic ECF and produce organic solutes to match intracellular osmolarity.

Question 7

What systems integrate fluid and electrolyte balance? How are they controlled and what is their response speed?

Answer 7

1. Cardiovascular
   
   • Neural control
   • Rapid
2. Respiratory
   
   • Neural control
   • Rapid
3. Renal
   
   • Endocrine and neuroendocrine control
   • Slower

Question 8

Which cells in the body respond to atrial filling?

Answer 8

Volume baroreceptors on the aorta.

Question 9

What creates concentrated urine? The concentration, or osmolarity, of urine is a measure of how much of what is excreted by the kidneys?

Answer 9

The intersitial space of the renal medulla. Concentration is a measure of how much water is excreted.

Question 10

If the kidneys are trying to remove excess water they will produce a _____ volume of _____ urine. This is known as diuresis.

Answer 10

Large, dilute.

Question 11

If the kidneys are trying to conserve water they will produce a _____ volume of _____ urine. This is known as antidiuresis.

Answer 11

Small, concentrated.

Question 12

How do the kidneys control the urine concentration? Where does this occur?

1. What happens in the production of dilute urine?
2. What happens in the production of concentrated urine?

What mechanism are these changes made by?

Answer 12

They vary the amounts of water and Na+ reabsorbed in the distal nephron (distal tubule and collecting duct).

1. The distal nephron must reabsorb solute without allowing water to follow by osmosis.
2. The distal nephron must reabsorb water and little solute.

This is done adding or removing water pores (AQP2) in the apical membrane under the direction of the hormone vasopressin (AVP).

Question 13

The insertion of AQP2 is a _____ process, depending on the amount of AVP present.

Answer 13

Graded. It is not all or one.

Question 14

What 4 stimuli control vasopressin secretion?

Answer 14

1. Blood pressure
2. Blood volume
3. Osmolarity
   
   • Increased osmolarity is the most potent stimulus of AVP secretion
4. Circadian rhythm (dies down at night)

Question 15

Production and secretion of vasopressin:

1. Controlled by what cells?
2. What is osmolarity monitored by?
3. How do these signal the control cells?

Answer 15

1. Magnocellular neurosecretory cells (MNC’s) in the hypothalamus
2. Osmolarity is monitored by osmoreceptor neurons.
   
   • Stretch sensitive neurons that increase firing rate as osmolarity increases (shrink)
3. High osmolarity causes firing of the osmoreceptor neurons, signaling the MNC’s, causing the release of AVP.

Question 16

Activity of MNC’s

1. Hypertonic solution:
2. Set point:
3. Hypotonic solution:

Answer 16

1. Hypertonic solution: increased AP’s, increased AVP release, antidiuresis
2. Set point: antidiuresis and diuresis both adjust to meet the set point level
3. Hypotonic solution: decreased AP’s, decreased AVP, diuresis

MNC’s are always active to some extent

Question 17

AVP is important for water reabsorption out of the nephron, but the high osmolarity within the medullary interstitium is necessary for what?

Answer 17

To create the concentration gradient for osmotic movement of water out of the collecting duct.

Question 18

What creates the hyperosmotic interstitium and why isn’t it reduced as water is reabsorbed? (2 reasons)

Answer 18

The renal medulla

1. Renal countercurrent exchange system
2. Urea

Question 19

What are the components of the renal countercurrent exchange system? What are the main roles of each?

Answer 19

1. Loop of Henle (countercurrent multiplier)
   
   • Descending limb: allows water to follow to follow its osmotic gradient into the increasingly hypertonic interstitium but does not allow solutes to be transported.
   • Ascending limb: actively transports solutes (Na+, Cl-, K+) into the interstitium. Filtrate leaving is hypoosmotic.
   • Main job: create the hypertonic interstitium
2. Peritubular capillaries (vasa recta) (countercurrent exchanger)
   
   • Moves in the opposite direction to the multiplier.
   • Removes water
   • Main job: prevent the washout (dilution) of the hypertonic interstitium

Question 20

25% of sodium and potassium reabsorption occurs in the ascending limb of the Loop of Henle. This is done using _____ transport and what kind of transporter? Describe it’s mechanism.

Answer 20

Active transport using NKCC transporters on the apical membrane. Uses energy stored in the Na+ concentration gradient to move Na+, K+ and 2 Cl- into the epithelial cells. Na+ is pumped against it’s concentration gradient on basolateral membrane.

Question 21

Why doesn’t the water entering the interstitium via the decending limb dilute the hyperosmotic medulla?

Answer 21

The opposite direction loop of the vasa recta picks some solute up and loses some water as it travels by the ascending limb creating hyperosmotic blood. This then creates a gradient allowing much of the water transported from the ascending limb to move into the vasa recta.

Question 22

What role does urea play in the creation of the hyperosmotic interstitium?

Answer 22

Large amounts of urea in the medulla interstitium contribute to the hyperosmotic state.

Question 23

Aldosterone

1. What is it?
2. Where is it produced?
3. What role does it play?
4. What channels does it act on?

Answer 23

1. Steroid hormone
2. Produced in the zona glomerusola cells
3. Responsible for altering Na+ reabsorption and K+ excretion.
4. ENaC (Na+ reabsorption channel) and ROMK (K+ excretion channel)

Question 24

When aldosterone binds to _____ receptors in _____ cells, what two things happen?

Answer 24

Cytoplasmic mineralocorticoid receptor in P cells.

1. Increased opening of Na+ channels and possibly K+ channels, enhancing Na+ reabsorption and K+ excretion
   
   • Increased Na+ entry speeds up Na+-K+ pump, increasing reabsorption of Na+, while increasing intracellular K+, leading to increased K+ secretion
2. Hormone ligand complex transports to cell nucleus, increasing transcription of apical Na+ channels, apical Na/K pumps, and possibly apical K+ channels, further enhancing reabsorption and secretion

Question 25

What 3 things can trigger aldosterone release? What thing can inhibit it?

Answer 25

_Activate_: 1. Abnormally **large drop in Na+** 2. **K+** will act on the adrenal cortex to stimulate production, protecting the body from hyperkalemia 3. **RAS pathway**: decreased blood pressure usually controls aldosterone secretion initiating a pathway that results in the production of angiotensin II which triggers aldosterone release _Inhibit_: 1. **Increased osmolarity** acts on adrenal cortex during dehydration, inhibiting aldosterone release

Question 26

**Renin-angiotensin system/pathway** 1. Role? 2. Assists which reflex? 3. Works with what system? 4. Begins with secretion of what?

Answer 26

1. Maintains blood pressure 2. Assists baroreceptor reflex 3. Works with the cardiovascular control center 4. Begins with the secretion of renin

Question 27

Give three stimuli that begin the RAS. What are these all driven by?

Answer 27

1. **Low blood pressure in renal arterioles** causes granular cells to secrete renin 2. **Sympathetic neurons** activated by CVCC when blood pressure decreases terminate on granular cells to secrete renin 3. **Paracrine feedback (prostaglandins) from macula densa cells** signal to the granular cells to secrete renin These are all driven by a drop in blood pressure.

Question 28

What is the main role of renin?

Answer 28

To convert angiotensinogen to angiotensin I.

Question 29

What enzyme converts ANG I to ANG II?

Answer 29

Angiotensin converting enzyme (ACE).

Question 30

What are the 5 effects of ANG II?

Answer 30

1. Increases vasopressin secretion (ANG receptors in the hypothalamus) 2. Stimulates thirst 3. Vasoconstriction 4. Increased sympathetic output to heart and blood vessels (ANG II receptors in the CVCC) 5. Increases proximal tubule Na+ reabsorption (apical Na+/H+ exchanger), increasing water reabsorption

Question 31

**Atrial natriuretic peptide (ANP)** 1. Where is it produced and secreted from? 2. What stimulates production? 3. What is its role? 4. What is its receptor and how does it work?

Answer 31

1. Produced and secreted by specialized myocardial cells primarily in the atria of the heart. 2. Stimulated by increased stretch of the atria. 3. Causes loss of water and Na+ (works in complete opposition to ANG II). 4. ANP receptor, acts through a cGMP second messenger system

Question 32

ANP primarily affects 4 regions of the body, what are they and how does ANP affect them?

Answer 32

1. **Kidney** * Relaxes afferent arterioles (increases GFR) * Reduces renin release from granular cells * Reduces Na+ reabsorption at the collecting duct 2. **Hypothalamus** * Reduces AVP release 3. **Adrenal cortex** * Inhibits aldosterone release 4. **Medulla** * Acts on the CVCC to decrease blood pressure