Distal Convoluted Tubule And Collecting Duct

Question 1

A 19 year old man is diagnosed with diabetes insipidus which is a disease of the vasopressin system. Which serum osmolyte is likely to be the most important in controlling the release of vasopressin in this man?

Answer 1

Sodium

Question 2

Aldosterone is a mineralocorticoid produced by the adrenal cortex. Which of the following statements about aldosterone is correct?

Answer 2

reduces sodium and water loss through the urine

Question 3

Aldosterone is a key hormone involved in salt and water homeostasis. Which effect does aldosterone have on transporter proteins in the distal convoluted tubule?

Answer 3

Increase in Sodium - Potassium exchange transporters

Question 4

Function of DCT

Answer 4

Fine tuning and regulation of Na+, K+, Ca2+ and Pi
Separation of Na+ from H2O
Continues active dilution of urine by reabsorption of Na+ in a water impermeable setting

Question 5

What transporter aids reabsorption of Na+ and Cl- in DCT

Answer 5

NCC (sodium chloride cotransporter)

Question 6

2 cell types of DCT

Answer 6

Principle cells
Intercalated cells

Question 7

What do principle cells respond to

Answer 7

Aldosterone and vasopressin

Question 8

Effect of aldosterone on principle cells

Answer 8

Increased expression of ENaC, ROMK, Na/K ATPase and H ATPase

Question 9

Effect of vasopressin on principle cells

Answer 9

Insertion of AQP 2 on apical membrane - water reabsorption

Question 10

Function of intercalated cells

Answer 10

Exchanging acids and bases

Question 11

What do alpha intercalated cells secrete

Answer 11

Acid

Question 12

What do beta intercalated cells secrete

Answer 12

Bicarbonate

Question 13

Sodium reabsorption in distal tubule

Answer 13

Active transport of Na+ via basolateral Na/K ATPase pump out of proximal tubule cell into interstitial fluid- low intracellular concentration of Na+ compared to tubular lumen so Na+ moves down gradient into tubular epithelial cells
Secondary active transport of glucose and phosphate into cells
H+ exchanged for Na+ = lumen becomes acidic

Question 14

What promotes sodium reabsorption in DCT

Answer 14

Aldosterone

Question 15

Mechanism of aldosterone

Answer 15

Diffuses through membrane (steroid)
Binds to mineralocorticoid receptor complex intracellularly
Complex binds to MRE in the nucleus and increases protein synthesis for ENaC, ROMK, Na/K ATPase and H ATPase

Question 16

What type of hormone is aldosterone

Answer 16

Steroid

Question 17

What are co-transported with Na+ in the DCT

Answer 17

Glucose
Phosphate

Question 18

How does DCT maintain acid-base balance

Answer 18

Secretes H+ (derived from intracellular carbonic anhydrase) by H ATPase H/K counter transporter - K+ brought into the cell

Question 19

Effect of aldosterone

Answer 19

Increases Na+ reabsorption in DCT and subsequent H2O reabsorption
More K+ lost in collecting duct due to Na/K ATPase
Increases H+ secretion in collecting duct
Promotes Na+ reabsorption in gut and sweat gladns

Question 20

What causes the release of aldosterone

Answer 20

RAAS
Sympathetic
Afferent arterioles wall tension
Paracrine factors
Hyperkalaemia
Hyponatraemia

Question 21

Why does hyperkalaemia causes the release of aldosterone

Answer 21

Causes secretion of K+ via Na/K ATPase

Question 22

Why does hyponatraemia causes the release of aldosterone

Answer 22

Retention of Na+

Question 23

What is ANP

Answer 23

Atrial natriuretic peptide
28 amino acid peptide cleaved from a precursors

Question 24

What causes the release of ANP

Answer 24

Stretch of atria due to:
Large circulating volume
High venous return
Increase in plasma Na+

Question 25

Where is ANP synthesised and secreted from

Answer 25

Cardiac atrial cells - especially right atrium

Question 26

Effects of ANP

Answer 26

Inhibits Na+ reabsorption by blocking ENac and Na/K ATPase Renal vasodilator of afferent arterioles Inhibits aldosterone secretion Blocks renin secretion Blocks effects of angiotensin

Question 27

How does ANP inhibit Na+ reabsorption

Answer 27

Blocks ENaC and Na/K ATPase

Question 28

ANP as a renal vasodilator

Answer 28

Afferent arterioles dilation Increases GFR increases Na+ excretion (natriuresis)

Question 29

ANP and aldosterone

Answer 29

Inhibits secretion from Zona glomerulosa Increases Na+ secretion

Question 30

ANP and renin

Answer 30

Blocks renin secretion in afferent arterioles Causes dilation, increases pressure in glomerular capillaries increasing GFR, increases tubular flow rate so increases Na+ loss

Question 31

How does ANP block the effects of angiotensin

Answer 31

Blocks the H/Na exchange and Na/K ATPase

Question 32

When is parathyroid hormone released

Answer 32

In response to low plasma Ca2+ concentration

Question 33

Effect of parathyroid hormone

Answer 33

Reduces phosphate uptake Stimulates formation of vitamin D

Question 34

Where is vitamin D formed

Answer 34

Kidneys

Question 35

How does parathyroid hormone work

Answer 35

Binging with a receptor causes an increases in Ca2+ uptake from the tubule which is carried across the basolateral membrane by Ca/H ATPase and Ca/H counter transporter

Question 36

Function of collecting duct

Answer 36

Acid-base balance Regulation of salt H2O reabsorption

Question 37

What percentage of glomerular filtrate reaches the collecting duct

Answer 37

15%

Question 38

What volume of glomerular filtrate reaches the collecting duct

Answer 38

20-25 L

Question 39

Concentration of fluid entering collecting duct

Answer 39

100 mOsm

Question 40

Why is the collecting duct impermeable to water

Answer 40

Cells have very tight junctions

Question 41

What urine concentration can it reach in the collecting duct if vasopressin active

Answer 41

1000-1200 mOsm

Question 42

What is vasopressin

Answer 42

9 amino acid peptide (nonapeptide) Cleaved from a larger precursor

Question 43

Where is vasopressin synthesised

Answer 43

Magnocellular cells in the supraoptic and paraventricular nuclei of hypothalamus

Question 44

Where is vasopressin stored

Answer 44

Granules with neurophysin

Question 45

Where is vasopressin secreted from

Answer 45

Posterior pituitary

Question 46

How is vasopressin transported from the hypothalamus to pituitary

Answer 46

Neurohypophysis in neurones

Question 47

What controls the release of vasopressin

Answer 47

Hypothalamic osmoreceptors

Question 48

How sensitive are osmoreceptors

Answer 48

Very Can detect changes as small as 1-2% in osmolarity

Question 49

What substances affect vasopressin secretion

Answer 49

Alcohol MDMA (ecstasy) Nicotine

Question 50

How does alcohol effect vasopressin secretion

Answer 50

Decreases Results in hydration

Question 51

How does MDMA effect vasopressin secretion

Answer 51

Inhibits Results in dilute blood which leads to seizures and fits

Question 52

How does nicotine effect vasopressin secretion

Answer 52

Increased

Question 53

Half life of vasopressin

Answer 53

15 mins- allows for quick adaptations to osmolarity changes

Question 54

Mechanism of vasopressin

Answer 54

Binds to V2R receptors (Gs GPCR) Protein kinase A phosphorylates serine 256 sites on tetrameter of vesicle If 3 out of 4 sites arephosphorylated the vesicle is shuttled to apical surface where AQP2 is inserted

Question 55

What channel protein transports water out of colllecting ducts

Answer 55

AQP2

Question 56

What receptor does vasopressin bind to in kidneys

Answer 56

V2R receptors

Question 57

What does binding of vasopressin to V2R receptors trigger

Answer 57

Protein kinase A to phosphorylate serine 256 sites on tetrameter of vesicle

Question 58

How many serine 256 sites must be phosphorylated for vesicle to fuse with apical membrane in collecting duct

Answer 58

3 out of 4

Question 59

How many times can shuttling back of the AQP2 occur before the protein is degraded

Answer 59

3/e

Question 60

What happens once water is reabsorbed via AQP2 on apical membranes

Answer 60

Escapes through AQP3 and AQP4 channels on basolateral membrane

Question 61

How does vasopressin affect arterioles

Answer 61

Constriction which helps restore arterial blood pressure to normal

Question 62

What stimulates thirst

Answer 62

Increase in plasma osmolarity Decrease in extracellular fluid

Question 63

Vasopressin and urea

Answer 63

Causes insertion of urea transporters (UTA) onto the membrane Vasa recta contain UTB Try and keep the interstitium high in urea so we can excrete urine at a high concentration - stops osmotic effect Vasopressin helps maintain the hyperosmolarity of medulla by increasing urea permeability of collecting duct

Question 64

Where are baroreceptors that control vasopressin secretion located

Answer 64

CVS eg aortic arch and carotid sinus

Question 65

What causes baroreceptors to decrease their firing

Answer 65

CV pressures decrease eg reduced blood pressure

Question 66

Baroreceptors and vasopressin secretion

Answer 66

Decrease firing when CV pressures decrease Baroreceptors transmit fewer impulses via afferent neurones and ascending pathways to hypothalamus—> vasopressin secretion

Question 67

Baroreceptors and vasopressin decrease

Answer 67

Increase CV pressures Increased baroreceptors firing Decrease vasopressin secretion

Question 68

Sensitivity of baroreceptor reflex of vasopressin

Answer 68

High threshold = sizeable reduction in CV pressure required to trigger it Les sensitive than osmoreceptors reflex

Question 69

Transporters on apical membrane of DCT

Answer 69

NCC (na and Cl) Ca2+

Question 70

Aldosterone action

Answer 70

Increases transcription (steroid receptor) of ENaC (and NaKATPase) This increases apical Na influx This charge movement facilitates K efflux Thus aldosterone drives both Na reabsorption and K secretion