(uro-renal) renal regulation of water & acid-base balance Flashcards
1
Q
what is osmolarity?
A
the concentration of osmotically active particles in solution
(quantitatively expressed is osmoles of solute per litre of solution)
2
Q
what is the equation for osmolarity?
A
concentration x no. of dissociated particles
Osm/L OR mOsm/L
3
Q
what are the units of osmolarity?
A
Osm/L OR mOsm/L
4
Q
calculate the osmolarity for 100 mmol/L glucose and 100mmol/L NaCl
A
osmolarity for glucose
= 100 x 1 = 100 mOsm/L
(one dissociated particle)
5
Q
calculate the osmolarity for 100mmol/L of NaCl
A
osmolarity for NaCl
= 100 x 2 = 200 mOsm/L
(two dissociated particles)
6
Q
what is the driving force for osmosis?
A
oncotic pressure/osmotic pressure
7
Q
what does the osmotic/oncotic pressure depend on?
A
directly proportional tot he number of solute particles
8
Q
what is the total fluid volume?
A
approx 60% of body weight
9
Q
describe the distribution of body fluid
A
2/3 = intracellular 1/3 = extracellular
of the extracellular fluid
- 1/4 = intravascular (plasma)
- 3/4 = extravascular
of the extravascular
- 95% = interstitial fluid
- 5% = transcellular fluid
10
Q
give an example of an intravascular fluid
A
plasma
11
Q
give an example of an extravascular fluid
A
interstitial fluid
transcellular fluid (peritoneal fluid, CSF)
12
Q
what are transcellular fluids?
A
fluid that fills up the spaces of chambers that are formed from the linings of epithelial cells
(CSF, peritoneal fluid)
13
Q
what separates intracellular fluid from extracellular fluid?
A
cell membranes
14
Q
water loss can either be regulated or unregulated - what are the four forms of unregulated water loss?
A
sweat
faeces
vomiting
evaporation from respiratory lining/skin
15
Q
water loss can either be regulated or unregulated - what is the one form of regulated water loss?
A
renal urine production
16
Q
what is positive water balance?
A
amount of water in the body is higher than what is required
17
Q
what is negative water balance?
A
amount of water in the body is less than what is required
18
Q
how do the kidneys respond to a positive water balance?
A
high water intake causes a positive water balance
= increased ECF volume = reduced sodium concentration = reduced plasma osmolarity = production of hypo-osmolar urine = osmolarity normalises as excess water is lost when the hypo-osmolar urine is excreted
19
Q
how do the kidneys respond to a negative water balance?
A
low water intake causes a negative water balance
= reduced ECF volume = increased sodium concentration = increased plasma osmolarity = production of hyperosmolar urine = osmolarity normalises as as much water as possible is retained (+ more water is drank) when the hyperosmolar urine is excreted
20
Q
besides hyper-osmotic urine production, what else causes the osmolarity to normalise in a negative water balance?
A
increased water intake due to thirst
+ combined w hyperosmolar urine production = normalises osmolarity
21
Q
what is the structural functional unit of a kidney?
A
nephron
22
Q
how much water is reabsorbed in the PCT?
A
67%
23
Q
how much water is reabsorbed in the thin descending limb of the loop of Henle?
A
15%
24
Q
what process does water reabsorption in the loop of Henle rely on?
A
osmosis (therefore, requires an osmotic gradient)
25
where in the loop of Henle can water be reabsorbed?
thin descending limb
| but defo not in the thick ascending limb
26
where in the loop of Henle can salts (Na+, Cl-) be reabsorbed?
thick ascending limb
| but defo not in the thin descending limb
27
what is an essential requirement for water reabsorption from the loop of Henle?
hyper-osmotic medullary interstitium
| to created the osmotic gradient required for water reabsorption form the LOH and the collecting duct
28
explain the process by which water is reabsorbed from the loop of Henle
sodium and chloride are reabsorbed both actively and passively reabsorbed din the thick ascending limb
produce a hyperosmotic medullary interstitium
water follows osmotic gradient into the medullary interstitium (from the thin descending limb tubular cells via aquaporin channels)
29
how much water is reabsorbed in the collecting duct?
variable amounts
30
why is the amount of water reabsorbed in the collecting duct variable?
depends on vasopressin action which determines the number of aquaporin channels embedded in the tubular cell membranes to facilitate water reabsorption
31
explain the process of countercurrent multiplication in the loop of Henle
active salt reabsorption in the thick ascending limb causes the medullary interstitium to become hyperosmotic (reducing tubular fluid osmolarity)
water follows into the medullary interstitium from the thin descending limb due to the osmotic gradient (increasing tubular fluid osmolarity)
32
why is countercurrent multiplication called so?
countercurrent = fluid movement in opposite directions in the ascending and descending limbs
multiplication = process continues to repeat itself
33
what is the minimum, maximum and range of osmolarities in the loop of Henle?
```
minimum = 300
maximum = 1200 (at tip of LOH)
```
= range due to repeated countercurrent multiplication cycles)
34
describe the osmolarity of the medullary interstitium as you do down the nephron
from the other medulla to the inner medullar
| = becomes more hyperosmolar
35
what is the vasa recta?
series of blood vessels surrounding the loop of Henle in the renal medullary region
(responsible for oxygen and nutrient transport)
36
what are UT-A1 transporters?
urea transporters found on the apical membranes of the tubular cells in the collecting duct
37
what are UT-A3 transporters?
urea transporters found on the basolateral membranes of the tubular cells in the collecting duct
38
explain how urea recycling occurs in the nephron
urea take up into tubular cells from tubular fluid via UT-A1 transporters
urea transported into medullary interstitium via the UT-A3 transporters (increasing interstitial osmolarity)
then either
1) urea transported into the vas recta via UT-B1 transporters
2) urea transported back into the tubular fluid via UT-A2 transporters in the thin descending limb
39
where does the urea go after the medullary interstitium?
then either
1) urea transported into the vas recta via UT-B1 transporters
2) urea transported back into the tubular fluid via UT-A2 transporters in the thin descending limb
40
what is the maximum possible concentration of urea in the medullary interstitum?
600 mmol/L
41
what are UT-B1 receptors?
urea transporters found on the vasa recta
42
what are UT-A2 receptors?
urea transporters found on the thin descending limb of the loop of Henle
43
what is the purpose of urea recycling?
to increase medullary interstitium osmolarity for
1) urine concentration
2) because urea excretion requires less water (so less water loss)
44
differentiate between the vasa recta and the peritubular capillaries
both have the same function of nutrient transport
- peritubular capillaries originate from the efferent arteriole and surround the renal cortex region mainly
- vasa recta are specialised peritubular capillaries that supply the renal medulla
45
how does vasopressin affect urea recycling?
vaspressin increases UT-A1 and UT-A3 numbers so increases urea uptake into the medullary interstitium
= making it more hyper-osmotic
46
how many amino acids make up vasopressin?
nine
47
what is the main function of vasopressin?
concentrates the urine by increasing water reabsorption from the collecting duct
48
where is ADH produced?
hypothalamic magnocellular neurones in the supraoptic and paraventricular nucleus
49
where is ADH stored?
posterior pituitary gland
50
what is the normal plasma osmolality in a healthy adult?
275-290 mOsm/kg H2O
51
how is the fluctuation in osmolality detected?
osmoreceptors in the hypothalamus
52
what change in osmolality is required for detection by osmoreceptors?
approx 5-10%
53
which factors stimulate ADH production?
increased plasma osmolality
hypovolemia (decreased blood pressure)
nausea
angiotensin II
nicotine
54
which factors inhibit ADH production?
decrease plasma osmolality
hypervolemia (increased blood pressure)
ethanol
ANP (atrial natriuretic peptide)
55
which receptor does ADH act on in the collecting duct?
V2 receptor on the basolateral membrane of the tubular cells
56
what kind of receptors are V2 receptors?
G-protein coupled
57
what are aquaporin 3 and aquaporin 4 channels?
water transporters on the basolateral membrane of the tubular collecting duct cells
58
what does the activation of the V2 receptors cause?
stimulates activation of adenylate cyclase = converts ATP to cAMP
activates protein kinase A
stimulates the migration of aquaporin 2 channels into the apical membrane to facilitate water reabsorption
59
what are aquaporin 2 channels and why are they important?
water transporters on the apical membrane of the tubular collecting duct cells
= facilitate water reabsorption from the tubular fluid
60
which aquaporin channels does ADH act on?
aquaporin 2 & aquaporin 3
61
what is diuresis?
increased dilute urine production
62
what are the ADH levels in diuresis?
low or zero
63
explain how diuresis occurs
-
64
how low can urine osmolality actually get?
as low as 50 mOsm/L
65
what is reabsorbed in the thin descending limb of the LOH?
water (passively)
66
what is reabsorbed in the thick ascending limb of the LOH?
Na+, Cl- (actively in the inner medullary region and passively in the outer medullary region)
67
describe the tubular fluid just at the end of the loop of Henle, prior to entering the collecting duct
hypoosmotic (due to ascending limb NaCl reabsorption)
68
what happens in the DCT that contributes to diuresis?
increased active Na+, Cl- reabsorption
| makes tubular fluid more hypoosmolar
69
what happens in the collecting duct that contributes to diuresis?
increased Na+ reabsorption
70
which transporter(s) is/are responsible for NaCl reabsorption in the thick ascending limb?
(basolateral) Na+-K+ ATPase, K+ - Cl- symporter
| (apical) triple transporter
71
which transporter(s) is/are responsible for NaCl reabsorption in the DCT?
(basolateral) Na+-K+ ATPase, K+ - Cl- symporter
| (apical) Na+ - Cl- symporter
72
in diuresis, why is water not reabsorbed in the DCT?
aquaporin 2 channels are absent in the DCT in diuresis
73
which transporter(s) is/are responsible for Na reabsorption in the collecting duct?
(basolateral) Na+-K+ ATPase
| (apical) Na+ channels
74
in diuresis, despite the low ADH levels, why does some water reabsorption still occur in the collecting duct?
there are still some aquaporins present so water reabsorption can still take place in the absence of ADH
75
what is antidiuresis?
production od low volumes of concentrated urine
76
what are the ADH levels in antidiuresis?
high
77
what three things does high ADH cause in antidiuresis?
(apical transporters)
thick ascending limb = triple transporter
DCT = Na+ - Cl- symporter
collecting duct = Na+ channels
78
how high can urine osmolality actually get?
1200 mOsm/L
| can produce as little as 0.5L of urine per day
79
explain how antidiuresis occurs
-
80
in anti-diuresis, why are large amounts of water reabsorbed in the DCT?
aquaporin 2 channels are present to facilitate water reabsorption
81
in anti-diuresis, why are large amounts of water reabsorbed in the collecting duct?
there is a gradient in the medullary interstitium = gets more hyperosmolar as you progress from inner medulla to outer medulla, down the nephron
medullary hyperosmolarity stimulates more water reabsorption
82
name three ADH-related clinical disorders
central diabetes insipidus
nephrogenic diabetes insipidus
syndrome of inappropriate ADH secretion (SIADH)
83
what causes central diabetes insipidus?
decreased/negligent production and release of ADH
84
what are the clinical features of central diabetes insipidus?
polydipsia
polyuria
(among others)
85
what is the treatment for central diabetes insipidus?
external ADH administration
86
what is SIADH?
syndrome of inappropriate ADH secretion
87
what causes SIADH?
increased production and release of ADH
88
what are the clinical features of SIADH?
hypervolemia
hyperosmolar urine production
hyponatraemia
89
what is the treatment for SIADH?
non-peptide inhibitor of ADH receptor
(conivaptan & tolvaptan)
= prevents aquaporin channel facilitation of water reabsorption
90
what is central/cranial diabetes insipidus?
impaired pituitary production of ADH leading to impaired water reabsorption in the renal collecting duct
(could be due to trauma or infection)
91
what is nephrogenic diabetes insipidus?
impaired response to adequate ADH production due to damaged or mutant renal V2 receptors or aquaporin 2 channels
= leading to impaired water reabsorption from the renal collecting duct
92
what causes nephrogenic diabetes insipidus?
less/mutant aquaporin 2 transporter
93
what are the clinical features of nephrogenic diabetes insipidus?
polydipsia
polyuria
(among others)
94
what is the treatment for nephrogenic diabetes insipidus?
thiazide diuretics + NSAIDs
| diuretics reduce filtration rate at Bowman's capsule so reduced volume of urine produced
95
true or false: ADH regulates the number of aquaporin channels on both the apical and basolateral membranes of the principal cells
true
ADH can either upregulate/downregulate aquaporin 2 (apical) & aquaporin 3 (basolateral) channels
96
true or false: the blood of a patient suffering from SIADH will slowly get more hyperosmotic
false
will become hypoosmotic as body conserves more water when not required
97
how are most bases excreted?
base excretion in faeces
98
how much metabolic acid is added to the body each day?
50-100 mEq/day
99
which ion is essential for metabolic acid neutralisation?
baicrbonate ion (HCO3-)
100
what is the ECF concentration of bicarbonate ions?
approx 350 mEq OR 24 mEq/L
101
why are bicarbonate ions important in the body?
neutralise the metabolic acids produced daily to prevent acidosis or other acid-base disorders
102
which enzyme catalyses the combination of carbon dioxide and water and what does this produce?
carbonic anhydrase
103
what does carbonic acid dissociate into?
H+ ions
HCO3- ions
104
what does the Henderson-Hasselbalch equation suggests about H+ ions and HCO3- ions?
[H+] = (24 x pCO2)/[HCO3-]
so the [H+] is directly proportional to the pCO2 = rises so H+ rises and falls so H+ fals
and the [H+] is inversely proportional to the [HCO3-] = rises so [H+] falls and falls so [H+ rises
105
what kind of acid-base disorder results from a rise or fall in the PCO2?
respiratory
| if pCO2 changes
106
what kind of acid-base disorder results from a rise or fall in the [HCO3-]?
metabolic
if [HCO3-] changes
107
how much of the bicarbonate in the tubular fluid is reabsorbed
approx 100% of the tubular fluid bicarbonate ions
108
which transporters are responsible for bicarbonate ion reabsorption in the PCT tubular cells?
apical = H+ excretion
- NHE3 (Na+-H+ antiporter)
- H+ ATPase
basolateral = HCO3- reabsorption
- Na+-K+ ATPase
- NBC1 (Na+-HCO3- symporter)
109
what are intercalated cells?
tubular cells involved in acid-base regulation
110
what is the function of alpha intercalated cells?
H+ secretion
| HCO3- reabsorption
111
what is the function of beta intercalated cells?
HCO3- secretion
| H+ reabsorption
112
which transporters are responsible for bicarbonate ion reabsorption in the DCT and collecting duct tubular cells?
alpha intercalated cells
- apical = H+ ATPase, H+-K+ ATPase
- basolateral = Cl- - HCO3- antiporter
beta intercalated cells
- apical = Cl- - HCO3- antiporter
- basolateral = H+ ATPase
(swapped apical and basolateral in one cell to give arrangement for the other)
113
what is glutamine important for in the PCT tubular cells?
glutamine produced two ammonium ions and one divalent ion
the divalent ion gives rise to two bicarbonate ions that are reabsorbed into the bloodstream
the ammonium ions are secreted into the tubular fluid via the Na+-H+ antiporter (substituted in place of H+)
114
how do the ammonium ions leave the PCT tubular cells and enter the tubular fluid?
via the Na+ - H+ antiporter
115
how are H+ ions secreted into the tubular fluid in the DCT and CD?
H+ ATPase
| H+ - K+ ATPase
116
explain how new bicarbonate ions are produced in the PCT tubule cells
glutamine produced two ammonium ions and one divalent ion
the divalent ion gives rise to two bicarbonate ions that are reabsorbed into the bloodstream
117
why is it important that the ammonium ions produced in new bicarbonate ion formation is excreted from the tubular cells?
if reabsobed and not excreted, they would then travel to the liver and produce one urea molecule and one proton
the proton produced would need to be neutralised by the newly gained bicarbonate ions, nullifying the gain
118
what are the two ways in which a net gain of bicarbonate ions is ensured in the tubular cells?
- ensuring the secretion of ammonium ions in the PCT (which would otherwise form protons in the liver, that need to be neutralised)
- providing non-bicarbonate buffers for H+ ion neutralisation in the DCT and CD
119
explain how new bicarbonate ions are produced in the DCT and collecting duct tubule cells
carbonic acid dissociated to produce H+ ions and HCO3- ions
the bicarbonate ions are reabsorbed into the bloodstream
the remaining H+ ions, instead of being reabsorbed and needing to be neutralised by the newly gained bicarbonate ions, are secreted
the secreted H+ ions are neutralised by other non-bicarbonate buffers, such as phosphate (HPO42-)
120
give an example of a non-bicarbonate buffer
HPO4(2-)
121
what does glutamine produce in the PCT tubular cells?
two ammonium ions and one divalent ion (latter produced two bicarbonate ions)
122
what happens to ammonia in the filtrate?
combines w a proton to form an ammonium ion to be excreted
123
what are the characteristics of metabolic acidosis?
increased [HCO3-]
| decreased pH
124
what are the characteristics of metabolic alkalosis?
decreased [HCO3-]
| increased pH
125
what are the characteristics of respiratory acidosis?
increased pCO2
| decreased pH
126
what are the characteristics of respiratory alkalosis?
decreased pCO2
| increased pH
127
a problem in which parameter indicates a respiratory imbalance?
pCO2
128
a problem in which parameter indicates a metabolic imbalance?
[HCO3-]
129
what is the compensatory response to metabolic acidosis?
hyperventilation
increased HCO3- reabsorption and production
130
what is the compensatory response to metabolic alkalosis?
hypoventilation
increased HCO3- excretion
131
what is the compensatory response to respiratory acidosis?
acute = intracellular bufffering (H+ ions produced
chronic = increased HCO3- reabsoprtion and production
132
what is the compensatory response to respiratory alkalosis?
acute = intracellular bufffering
chronic = reduced HCO3- reabsoprtion and production
133
why is hyperventilation a compensatory mechanism?
hyperventilation
= pCO2 decreased
= reduced H+ ion due to reduced carbonic acid
= pH rises again
134
why is hypoventilation a compensatory mechanism?
hypoventilation
= pCO2 increases
= increased H+ ion due to increased carbonic acid
= pH falls again
135
what is intracellular buffering in acute respiratory acidosis?
carbon dioxide in the cell produces carbonic acid which dissociates into a proton ion and a bicarbonate ion
the proton ion is neutralised by cellular proteins and so there is a net gain of a bicarbonate ion (contributes to increased pH)
136
what is intracellular buffering in acute respiratory alkalosis?
shifts the carbonic acid dissociation equation to the left so more carbonic acid is produced and fewer bicarbonate ions are produced
137
identify the acid-base disorder through analysis of the patient's data
```
pH = 7.2 (7.35-7.45)
[HCO3-] = 17 mEq/L (22-28)
pCO2 = 35 mmHg (35-35)
```
pH is reduced so acidosis
if respiratory = pCO2 should be higher BUT if metabolic = [HCO3-] should be lower, which it is so
= metabolic acidosis
138
identify the acid-base disorder through analysis of the patient's data
```
pH = 7.5 (7.35-7.45)
[HCO3-] = 17 mEq/L (22-28)
pCO2 = 35 mmHg (35-35)
```
pH is increased so alkalosis
if respiratory = pCO2 should fall, which it has BUT if metabolic = [HCO3-] should rise so
= respiratory alkalosis (w renal compensation)
