1
Q
What happens if there is a mutation in SGLT2?
A
- Familial renal glycossuria
- Increased urinary glucose
- Autosomal recessive
2
Q
When is aldosterone released?
A
1) Increase in plasma K by as little as 0.1mM
2) Decrease in plasma Na
3) Decrease in extracellular fluid volume
3
Q
What does renin do?
A
- Catalyses the conversion of angiotensin to angiotensis 1 (in the blood vessels)
- AGT1 -> AGT2 by Angiotensin converting enzyme in the capillaries (the bulk of this happens in the lungs where the capillary density is larger)
- Promotes the release of aldosterone from the zona glomerulosa
- AGT2 also causes vasocontriction
4
Q
What channels are present in the proximal tubule and what do they allow?
A
Apical: SGLT1/ SGLT2 = Glucose and sodium cotransporter Na/Amino acids = cotransporter NApiII = Phosphate/Na cotransporter NHE3 = Na/H symporter (H out Na in)
Basolateral
Na/KATpase = 3 NA out, 2 K in
K = K out
Na/HCO3 = 3 NA and 1 HCO3 out
5
Q
What is uraemia?
A
A group of symptoms associated with chronic renal faliure
6
Q
Symptoms of chronic renal faliure?
A
URAEMIA (a group of symptoms associated with chronic renal faliure)
- Hypertension
- Hyperkalemia
- Mild acidosis
- Nausea/ vomiting - due to increased cretanine and serum urea
- Calcification
- Amemia lethargy
7
Q
What is the pelvis of the kidney?
A
1 per kidney, urine flows from the calyx into here and then into the ureter
8
Q
What is different about the descending limb and the ascending limb of the loop of henle?
A
Decending- absorbs water but not ions
Acsending - absorbs ions but not water
9
Q
What are the roles of the principle cells?
A
1) Concentrate urine
2) Secrete K and H
3) Reabsorb Na and H2O
10
Q
What is the treatment for Liddle’s syndrome?
A
Amiloride, K sparing diuretic
- Blocks excess ENaC
11
Q
What are the 3 regions of the adrenal cortex?
A
- Zona reticularis
- Zona fasciculate
- Zona glomerulosa
12
Q
Where are hypothalamic receptors present and what do they detect?
A
- In the cell bodies of the neurosecretory cells in the supra-optic and and paraventricular nucleus in hypothalamus
- They detect changes in osmolality +/- 3mOsm
13
Q
Names of loop diuretics and what channel do they act on?
A
Bumetanide
Frusemide
Block the NKCC2 channel in the apical membrane of the TAL
14
Q
What are the medullary rays?
A
Part of the medulla, show the orientation of the blood vessels
15
Q
How does alcohol affect vasoreprssin release and what are the consequences?
A
- Inhibit release when osmolality is normal
- Less water reabsorbed
- Increase urine flow rate
- Dehydration
16
Q
What does aldosterone stimulate?
A
1) Resabsorption of Na
2) Secretion of K and H
3) Regulates the angiotensin system
17
Q
What is the hilus of the kidney?
A
The point in the kidney where the ureter leaves
18
Q
What is the progression of chronic renal faliure?
A
- Thickening of the glomeruli membrane
- Causes glomerulosclerosis (scarring)
- Tubular atrophy (death of nephron and kidney)
- Interstitial inflammation
- Fibrosis (reduce in renal size)
19
Q
What are the 3 types of diuretics and where do they act?
A
Loop diuretics - loop of henle
Thiazide diuretics - Early distil tubule
K sparing diuretics - Late distil tubule
20
Q
How is Bartters symptoms different to Gittlemans syndrome?
A
Bartters involves hypercalciuria
Gittlemans involves hypocalciuria
21
Q
What is the glomerulus?
A
- A capillary bed embedded in the beginning of the nephron which filters the plasma
- Has afferent and efferent arterioles
- Liquid and ions are filtered though and proteins don’t
22
Q
What is the difference between superficial and juxtamedullary nephrons?
A
Superficial
- Regulates urine
- 85% of nephrons
- Glomerulus and bowmans capsule is in the outer cortex
Juxtamedullary
- Fine tunes urine
- 15% of nephrons
- Glomerulus and BC on the borderline between the cortex and the medulla
23
Q
Where does aldosterone act?
A
Late distil tubule and cortical collecting duct
24
Q
What is the transport maximum for glucose?
A
375mg/min
25
What is the structure of the alpha intercalated cell?
Apical:
H ATPase - H out
Basolateral:
Cl channel - Cl out
AE1 - Cl in, HCO3 out
26
What does the release of renin cause?
1) Increase Na reabsorption
2) Increase in extracellular fluid
3) Blood pressure goes to normal
27
What do angiotensin converting enzyme cause?
Less constriction and less water retension
28
4 abnormalities of the kideny?
1) Horseshoe kidney, remain fused
2) Ectopic kidney, one or more kindeys form in the pelvis but they are normal
3) Polysystic kidney - kidneys are enlarged to 30cm
4) Renal agensis - kidney doesn't develop. Incompatible with life
29
What is minimum flow rate?
300ml
30
What does renin-angiotensin regulate?
- Body fluid volume
| - Plasma K and Na
31
What percentage of fluid is extracellular?
38%
| 28% Intersitial, 7% plasma, 3% transcellular
32
Causes of chronic and acute renal faliure?
Chronic:
Hypertension
Diabetes mellius
PKD
Acute:
Pre renal
Renal
Post renal
33
What are diuretics?
- Drugs which increase the flow rate of urine
| - Treat hypertension and treat chronic renal faliure
34
Example of a thiazide diuretic and what does it d?
Chlorothiazide
- Targets NCC in the apical membrane of the early distil tubule
- Side effects are Gittleman's syndrome
35
Treatment of chronic and acute renal faliure?
Chronic:
Dialysis
Dieuretics
Acute:
Dialysis
36
How does ecstasy affect vasopressin release and what are the consequences?
- Increase release
- Retain water that would normally be secreted
- If coupled with drinking lots -> odema and swelling of the brain
37
What is the process of HCO3 reabsorption?
- HCO3 + H -> H2CO3 (carbonic acid)
- H2CO3 -.> H2O + CO2 (by carbonic anhydrase)
- H2O + CO2 diffuse into the membrane
- H2O + CO2 -> H2C03 (by carbonic anhydrase)
- H2CO3 -> H + HCO3
H out of apical membrane by NHE3
HCO3 out of basolateral membrane by Na/HCO3 cotransporter
38
What is an examples of a K sparing diuretic and where does it act?
- Amiloride
| - ENaC in the principle cells of the late distil tubule
39
What are the channels in the early distil tubule?
Apical:
NCC - cotransporter (one Na and one Cl in)
Mg channel
```
Basolateral:
Na/KATPase
K channel
Mg channel
CLCK and Barttin
```
40
Where is the site of action of vasopressin?
Collecting duct in the kidney
41
What does too much angiotensin 2 cause?
Hypertension
42
What percentage of fluid is intracellular?
62%
43
What causes central diabetes insipidus and what is the treatment?
Problems which the CNS at the level of the hypothalamus or the posterior pituitary
Nasal spray (containing synthetic vasopressin)
44
Principle cell model for vassopressin action?
- Vasopressin activates V2 receptors on the basolateral membrane
- Activation of protein kinase A (through G protein coupled pathway)
- PKA attaches to the vesicles containing AQP2 channels
- Channels fuse with the apical membrane
- Increases the amount of water absorbed
When VP levels drop:
-Endocytosis of the channels
45
What is Liddle's syndrome?
- Low aldosteone
- BUT increase in NA absorption through ENaC
- Increase in ENaC channels which can't be removed from the membrane
- Defect in endocytosis
- Too much Na, too much water reabsorbed
46
Intercellular composition of ions?
```
[K] = 144mM
[Na] = 10mM
[Other] = 40mM
```
```
[Cl] = 4mM
[Proteins] = 55mM
[Other] = 140mM
```
47
What are the symptoms of ROMK knockouts in mice and humans?
Mice
- Salt wasting
- Polyuria
- Acidosis
Humans
- Same symptoms but ALKALOSIS
48
Function of the calyx?
Part of the medulla, urine drains through here into the pelvis
49
What type of hormone is aldosterone?
A mineralcorticoid - regulates mineral content (especially Na and K)
50
2 types of cell in the late distil tubule?
Principle cell
| Intercalated cell - has alpha and beta configurations
51
What is renal faliure?
- When the glomerulus filtration rate falls below 125ml/min
| - Accumulation of serum urea and creatine which are toxic
52
Where is renin released from and how?
- From the juxtaglomerular apparatus (glomerulus and early distil tubule) in the kidney
In early distil tubule:
- Macular densa cells release compounds which act on the afferent arteriole in response to urine flow rates
In glomerulus:
- Contains the afferent arterioles have granules containing renin, compounds cause renin release
53
What is the structure of the beta intercalated cell?
Apical:
AE1 - Cl in, HCO3 out
Basolateral:
Cl channel - Cl out
H ATPase - H out
54
What are the channels in the principle cell and what do they do?
Apical:
ENaC - 1 Na in
ROMK - 1 K out
AQP2 - H2O in
Basolateral:
Na/KATPase
Kir 2.3 - K out
AQP3 and AQP4 - water out
55
What causes the release of vasopressin?
- Increased plasma osmolality (how concentrated)
- Stress
- Dehydration
- Injest solute
56
When is renin released?
- In response to a fall in extracellular fluid volume, which causes a fall in the glomerular filtration rate and a fall in urine flow rate
57
Dimentions of the kideny?
150g
10cm x 5.5cm
Found between the 12th lumbar and the 3rd thoratic segment
58
How is vasopressin released?
- Activation of the hypothalamic receptors
- Action potential generated down the axon into the posterior pituitary gland
- Causes influx of Ca2+
- Fusion of vesicles containing vasopressin with the presynaptic membrane
- Vasopressin release into capillary bed
59
What is the transport maximum and what is it limited by?
- When the transport across the tubule has reached its maximum rate
- Limited by the number of carrier channels
60
What causes nephrogenic diabetes inspidus?
- No activation of PKA due to V2 defect
- AQP2 defect
- No treatment
61
What happens when injest salt?
- Vasopressin release downregulated
- If this didn't happen there would be a opposing system as vasopressin aims to increase ECF volume and aldosterone aims to decrease it
62
Where is aldosterone released from?
From the zona glomerulosa in the adrena cortex of the adrenal gland
63
Onset for chronic and actute renal faliure differences?
Chronic:
Irreverisble
Progressive
Decreased Hb and renal size
Acute:
Reversible
Short
64
What is albumin and why is it significant?
Small moleucular weight protein which is present in the ultrafiltrate but reabsorbed in the tubules
If still present in the turine - problem with the tubule
65
What are the side effects of loop diuretics?
```
Bartters-like symptoms:
Salt wasting
Hypokalemia
Hypotension
Alkalosis
Hypercalciuria
```
66
Extracellular composition of ions?
```
[K] = 5mM
[Na] = 140mM
[Other] = 8mM
```
[Cl] = 103mM
[Proteins] = 15mM
[Other] =36mM
67
What is pseuodohypoaldosteronism?
- High aldosterone
- BUT high salt loss (Na)
- Problem with the mineralcorticoid receptor
- No production of protein channels
68
Principle cell model of aldosterone?
- Steroid hormone, enters through the cell membrane
- Binds to intracellular mineralcorticoid receptor
- Moves into nucleus and stimulates RNA transcription
```
- Increase in the proteins which synthesise:
ROMK
Na/H exchanger
ENaC
Na/KATPase
```
- Increase capacity to reabsorb Na and secrete K and H
- Same mechanism as in the alpha intercalated cells
69
What are the channels present in the TAL and how does Mg and Ca move?
Apical:
NKCC2 - Na, K, 2 x Cl in
ROMK (kir 1.1) - K out
Basolateral:
Na/KATPase - 3 Na out, 2 K in
K channel
CLCK - Cl out, regulated by BARTTIN
Mg and Ca move by paracellular transport
70
What is the function of the loop of henle?
- To concentrate urine
| - Removal of forgein compounds from the body (penicillin)
Physiology and Pharmacology
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