Kidney III

Question 1

What is constant plasma osmolality maintained by?

Answer 1

1) Urine formation
2) Thirst

Plasma osmolality range: 280-295mOsm/kg
Urine osmolality range: 50-1200mOsm/kg

Question 2

Concentrated Urine value

Dilute urine value

Answer 2

Concentrated urine: >300mOsm/l
Obliged to eliminate 600mOsm/l of waste products each day. Max urinary conc possible is 1400mOsm/l
Obligatory water loss: 600/1400=0.428L/day

Output <0.428L/day = ‘Oliguria’

Dilute urine: <300mOSm/l
Min urinary possible is 50mOsm/l (a lot of water conc!).
Max urine output ~23L/day

Normal urine output is ~1-2L/day
Output >2L/day = ‘Polyuria’

Question 3

Why would obligatory water loss increase?

Why would healthy urine may not be clear?

Answer 3

> person has experienced tissue trauma (increased waste products)

> person is fasting (generate more waste products)

Healthy urine may not be clear bc may be a sign of water intoxication OR disease

Question 4

Describe Oliguria, Polyuria, Diuresis

Answer 4

Oliguria - Output<0.428L/day

Polyuria - Output>2L/day

Diuresis - Excessive production of urine (w water)
Anti-diuresis - Less water excreted in urine

Question 5

Define Osmolar clearance

Answer 5

The clearance of all osmotically active particles can be calculated in a similar manner to the clearance of individual substances.
Fasting Cosm ~2-3ml/min

Question 6

Define Free water clearance

Answer 6

Used to assess renal function

Reflects the ability of the kidneys to excrete dilute or concentrated urine.

Calcuated using Cosm eqaution, with a V - in front.

Possible C H2O range -1.3 to 14.5 ml/min
Lowest: max anti-diuresis
Highest: complete absence of ADH

> 0 indicates hypo-osmotic urine
=0 indicates iso-osmotic urine w/r to plasma
<0 indicates hyper-osmotic urine

Question 7

Effect of Low and High water intake?

Answer 7

Low intake: increase plasma osmolality - detected by osmoreceptors (sends signals to posterior pituitary). It releases increased ADH into blood. Circulates in kidneys, where increased water reabsoprtion occurs at the level of collecting duct.
Outcome - less water excreted in urine

High intake: decrease plase osmolality - detected by osmoreceptors

Question 8

Function of osmoreceptors

Answer 8

Located near the hypothalamus

Osmoreceptors in the OVLT, MPN and SFO signal to magnocellular neurosecretory cells in paraventricular and supraoptic nuclei in hypothalamus.
These cells can produce and release ADH into blood through posterior pituitary

Precursor molecule passed along axon to terminal ending - posterior pituitary - to get ADH (9 A.A’s long)

Question 9

Why is ADH release into blood very effective

Answer 9

Plasma half-life short

ADH release rapid

ADH actions rapid - bc it’s thru a 2nd messenger effect

Question 10

What other factors affect ADH secretion

Answer 10

Blood pressure (10% decrease) + blood volume (5% decrease)

There has to be a 1% change in osmolality of these to cause an affect on ADH secretion

Question 11

Action of ADH on collecting duct

Answer 11

ADH acts on the level of V2-r on the basolateral membrane.
2nd messenger effect is mediated thru cAMP that’ll cause AQP2 insertion into the luminal membrane

Water can be reabsorbed

Question 12

Describe Diabetes Insipidus

Answer 12

Generate urine which has normal [Na+,K+,Cl-]
Characteristics:
> Urination (polyuria)
> Thirst (polydipsia)
> Nocturia too (frequently getting up to empty bladder)

Types:

1) Neurogenic (no ADH secretion) i) congenital
ii) head injury
2) Nephrogenic i) Inherited (V2-r/AQP2)
ii) Acquired

Question 13

Describe Osmotic Diuresis

Answer 13

[Na+,K+] will be higher than expected.

Reason for characteristics is increased urination due to small molecules (eg. excess glucose) in renal tubule lumen - so will get v.dilute urine aswell
Characteristics:
> Urination (polyuria)
> Thirst (polydipsia)

Mechanism

i) Increased blood [glucose]
ii) consequently, increased GF of glucose
iii) increased osmolarity in filtrate (affected gradient)
iv) Decreased H2O reabsoprtion from PT - other molecules also be altered

Later portions of nephron can not compensate

Question 14

Features of K+

Answer 14

> Most important intracellular cation in the body
5mM EC fluid, 150mM IC fluid.
Gradient main determinant of resting membrane potential
Ingest 40-120 mmoles K+ each day

Question 15

How do we maintain K+ balance across cells?

Answer 15

i) Renal excretion ~95mM
ii) GI loses (secreted into the colon, then expelled from the body in the feces) ~5mM
iii) Cellular shifts (redistributed)

(intake ~100 mM K+ per day)

Question 16

Describe renal handling of K+ (at PT)

Answer 16

Excretion involved filtration - kidney filters ~800mM/day - Reabsorption - ~95% of this is reabsorbed - and secretion.

~65% reabsorbed passively at PT

Majority of K+ movement is b/w cells by (not due to charge!) following movement of Na+ and H2O.

There are K+/Cl- channels at the basolateral side that move K+ into the interstitial fluid.
No inward K+ movement found at luminal membrane - only outwards

Question 17

Renal handling of K+ (at Thick ascending limb)

Answer 17

~30% reabsorbed at TAL

Via Na+/K+/2Cl- cotransporter expressed on luminal membrane.
Across the cell and out via K+/Cl- and K+ channels on basolateral.

Filtrate is +ve charged, therefore repels the K+.

Question 18

Renal handling of K+ (at Distal tubule)

Answer 18

~5% Reabsorbed at DT by intercalated cells

Via K+-H+ exchanger on luminal membrane

But outweighed by K+ secretion by principle cells
Exit routes:
i) K+ channels (ROMK, BK)
ii) K+/Cl- co-transporter

Secretion process is aided by the ATPase pump moving K+ into the cell across the basolateral membrane. Then excreted in the urine via i) and ii)

Question 19

Factors affecting K+ secretion by principal cells

Answer 19

1) factors affecting Na+ entry through Epithelial Na+ channels
2) Aldosterone stimulates K+ channels