Urinary Session 4 Flashcards
1
Q
Describe the osmotic status of sweat.
A
Hyposmotic
2
Q
What must happen in order to change plasma volume?
A
Isosmotic solution must be added or removed so osmolarity remains constant
3
Q
How is isosmotic volume added or removed from the plasma volume?
A
Movement of osmoles which water follows
4
Q
What method of reabsorption does sodium mainly undergo?
A
Transcellular active driven by 3Na-2K-ATPase on basolateral membrane
5
Q
In which part of the nephron is movement of water and sodium separated?
A
Descending thin limb and ascending thin and thick limbs of Henle’s loop
6
Q
What percentage of sodium in the filtered load is reabsorbed in the PCT?
A
67
7
Q
How does the percentage of water and sodium reabsorption from the filtered load in the PCT compare and why?
A
Approximately equal due to isosmotic reabsorption
8
Q
What percentage of water in the filtered load is reabsorbed in the ascending limbs of Henle’s loop and the DCT?
A
0%
9
Q
What is renal sodium excretion altered by?
A
Changes in osmotic and hydrostatic pressure in peritubular capillaries
10
Q
What does an increase in oncotic or hydrostatic pressure in the peritubular capillaries cause?
A
Inhibition of sodium reabsorption leading to decreased water reabsorption
11
Q
What is PCT sodium reabsorption stimulated by?
A
RAAS
12
Q
What are the target cells for aldosterone?
A
Principal cells of DCT and CD
13
Q
What does chloride absorption depend on?
A
Sodium reabsorption
14
Q
Why is chloride reabsorption important?
A
To maintain electroneutrality
15
Q
What must a finite volume of filtrate contain in terms of ions?
A
Anions=cations
16
Q
What main method of reabsorption is used for chloride ions?
A
Transcellular active coupled to 3Na-2K-ATPase
17
Q
Is paracellular reabsorption possible with chloride ions?
A
Yes
18
Q
Which sodium transporters are found in the PCT tubular cells?
A
Na-H antiporter
Na-glucose symporter
Na-a.a. cotransporter
Na-Pi PTH transporter
19
Q
Can the proportions of salts in the filtrate of the PCT vary as long as the osmolarity is constant?
A
Yes
20
Q
Why does the proportion of chloride in the filtrate of the PCT increase?
A
Chloride reabsorption lagers behind so as everything else is removed its relative proportion increases
21
Q
Why are glucose, a.a. and lactate transporters not needed in the distal PCT?
A
Fast, preferential reabsorption means that almost 100% is absorbed very quickly
22
Q
What compensates for loss of glucose in S1 of the PCT to keep osmolarity constant?
A
Increasing urea and chloride concentration down the segment
23
Q
What does the compensation of loss of glucose provide for S2-3 of the PCT?
A
Provide chloride concentration gradient for reabsorption
24
Q
What type of sodium transporters are seen in S1 of the PCT?
A
Co transporters
25
Which sodium transporter is found in the apical membrane along the length of the PCT?
Na-H exchanger
26
Describe the permeability of the PCT to water.
Very permeable
27
How is chloride reabsorbed in S2-3 of the PCT?
Intra- and paracellularly
28
What favours water uptake from the lumen in S2-3 of the PCT?
Presence of oncotic proteins in the peritubular capillaries
29
What increases uptake into the capillaries surrounding the PCT?
Increased osmolarity of the interstitial spaces
Increased hydrostatic forces in the interstitium
Increased oncotic force from cells and proteins in peritubular capillaries
30
What is the first line of defence in autoregulation of GFR?
Myogenic action and tubulo-glomerular feedback
31
Why is the first line of defence in autoregulation of GFR not always sufficient?
Not instantaneous
| Not always able to mount a big enough response
32
What is the second line of defence in maintaining constant GFR via autoregulation?
Glomerulotubular balance to ensure 67% of filtered sodium is reabsorbed regardless of the amount of filtration
33
What is the benefit of using glomerulotubular balance when GFR has varied widely?
Blunts extreme sodium excretion as a response to GFR changes that have not been corrected so the rest of the tubule can function
34
What is found between tubular cells of the thick and thin descending limbs of Henle's loop?
Loose junctions
35
What is the purpose of increasing intracellular sodium concentration in the thick and thin ascending limbs of Henle's loop?
Allow paracellular reabsorption of water
36
What is the purpose of allowing paracellular absorption of water in the thick and thin descending limb of Henle's loop?
Concentrates sodium and chloride in lumen ready for active transportin the ascending limb
37
What is found between tubular cells of the thin ascending limb of Henle's loop?
Tight junctions
38
What type of sodium reabsorption occurs in the thin ascending limb of Henle's loop?
Passive paracellular
39
What is the purpose of ROMK in the apical membrane of thick ascending limb tubular cells?
Leak K+ into the lumen where it is in low concentration in the filtrate so this does not become a limiting factor for reabsorption
40
Which part of the nephron is most sensitive to hypoxia and why?
Thick ascending limb of Henle's loop due to high energy demand
41
Which transporter facilitates sodium reabsorption in the thick ascending limb of the loop of Henle?
NaKCl2
42
What type of transporter is NaKCl2?
Symporter
43
What is found between cells of the thick ascending limb of Henle's loop?
Tight junctions
44
What type of sodium transporter is found in the apical membrane of the early DCT?
NaCl symporter
45
Describe the permeability of the early DCT to water.
Low
46
What is the osmotic state of fluid that enters the early DCT?
Hyposmotic
47
What is reabsorbed in the early DCT via PTH using an unknown mechanism?
Calcium
48
How is sodium reabsorbed in the early DCT?
Active transport
49
What percentage of filtered sodium is reabsorbed in the early DCT?
~5-8%
50
What is the osmotic state of fluid which exits the early DCT?
More hyposmotic that when it entered
51
How can cortical and medullary CD cells be distinguished?
Have different transporters
52
What apical sodium transporter is found in the late DCT and collecting duct tubular cells?
ENaC
53
Where is the filtrate in the nephron fine tuned in response to a variety of different stimulants?
Late DCT and collecting duct
54
Which two distinct cell types make up the late DCT and collecting duct?
Principle cells
| Type B intercalated cells
55
What is the ratio of the two types of cells found in the late DCT and collecting duct?
70% principal cells
| 30% type B intercalated cells
56
What creates the -ve lumen charge in the late DCT and CD which drives paracellular chloride uptake?
Active Na+ uptake via a channel not cotransporter so no accompanying anion movement
57
What effect does ADH have on principal cells?
Varies aquaporins for variable water uptake
58
What is the function of type B intercalated cells?
Active reabsorption of chloride
| Secretion of H+/HCO3-
59
How can type B intercalated cells be distinguished from principal cells on histological examination?
Darker staining nuclei
60
What system allows increased excretion of sodium and therefore water when increased circulating volume is exerting pressure on the filtration system?
Pressure natriuresis and diuresis
61
What does an increase in renal after BP cause to happen to transporters in the PCT?
Decreases expression of Na-H antiporter and Na-K-ATPase
62
What is the result of changes to transporters in the PCT caused by an increase in renal artery BP?
Decreased reabsorption of sodium and water in PCT:
Increased sodium excretion = pressure natriuresis
Increased water excretion = pressure diuresis
63
Do GFR autoregulation mechanisms still apply in pressure natriuresis and diuresis?
Yes
64
What in addition to pressure natriuresis and diuresis decreases fluid absorption in an increase of BP?
Increased BP --> increased peritubular capillary pressure --> increased fluid absorption
65
What is the pressure natriuresis and diuresis system independent of?
Vasomotor activity
66
Will urine always be isotonic when an isotonic volume is excreted to decrease blood volume?
No
67
Why do pressure natriuresis and diuresis occur together?
Lack of independent control
68
What does the degree of pressure natriuresis and diuresis depend on?
Volume status:
Increased ECF = high renal artery BP --> high pressure N&D
Decreased ECF = low renal artery BP --> low pressure N&D
69
What is the major osmotic ally effective solute in control of effective circulating volume?
Sodium
70
Where are nerve endings that are sensitive to stretch located which aid in acute regulation of BP?
Carotid sinus
| Aortic arch
71
How do baroreceptors conduct signals to allow for acute regulation of BP?
Baroreceptors --> afferent pathways --> coordinating centre in the medulla --> efferent pathways
72
How is BP regulated in the short term?
Adjustment of parasympathetic input to peripheral resistance vessels to alter TPR
73
What happens to baroreceptors in the carotid sinus and aortic arch in long term raised BP?
Baroreceptor firing threshold resets so is still present but not constantly acting
74
What are the four medium/longer-term mechanisms of BP control?
RAAS
Sympathetic nervous system
ADH
Atrial natriuretic peptide
75
How does the action of atrial natriuretic peptide (ANP) act differently to the other systems of longer term BP control?
Acts to decreases plasma volume whereas others act to increase
76
Which fluid compartment is plasma part of?
Extra cellular fluid
77
How is the RAAS stimulated?
Decreased NaCl to distal tubule
Decreased BP in afferent arteriole
Sympathetic stimulation of beta-1-adrenoceptors
78
What is released by the macula densa and detected by baroreceptors in the RAAS?
Local mediators
79
What is the reaction to local mediator detection by baroreceptors in the RAAS?
Renin release from granular cells of the afferent arteriole in the juxtaglomerular apparatus
80
Where is angiotensinogen synthesised?
Liver
81
What is angiotensinogen cleaved by?
Renin
82
What is angiotensinogen cleaved into?
Angiotensin I
83
What converts angiotensin I to angiotensin II?
Angiotensin converting enzyme
84
Where is ACE found?
Endothelial cells in non-specific amounts (lots in the lungs)
85
What additional action does ACE have to its angiotensin converting function?
Breaks down bradykinin into peptide fragments
86
Why are angiotensin II antagonists sometimes used instead of ACE inhibitors?
To prevent the increase in bradykinin caused by the inhibition of ACE which leads to a dry cough
87
Which type of angiotensin II receptors carry out the main physiological actions identified with angiotensin II?
AT1
88
What type of receptor is AT1?
GPCR
89
At what sites are angiotensin receptors found?
```
Arterioles
Kidney
SNS
Adrenal cortex
Hypothalamus
```
90
What does angiotensin II acting on receptors in arterioles cause?
Vasoconstriction
91
What does angiotensin II acting on receptors in the kidney cause?
Sodium reabsorption
92
What does angiotensin II acting on receptors in the SNS stimulate?
Increased noradrenaline release
93
What effects does angiotensin II have on the adrenal cortex and hypothalamus?
Adrenal cortex: increases aldosterone
| Hypothalamus: increases thirst --> increases ADH release
94
How does angiotensin II stimulate sodium reabsorption at the kidney?
Vasoconstriction of afferent and efferent arteriole to decrease GFR
Stimulates NHE3 in apical membrane of principle cell
95
What is the action of aldosterone release from the adrenal cortex?
Activates apical ENaC and K+ channel
| Increases basolateral sodium extrusion via 3Na-2K-ATPase
96
Why does aldosterone increase receptor expression?
It is a steroid hormone
97
What effect does increased levels of sympathetic stimulation in the glomerulus have in longer term BP control?
Causes arteriole vasoconstriction --> decrease GFR --> decrease sodium excretion
98
What is the affect of sympathetic stimulation on the PCT?
Directly activates apical Na/H exchanger and basolateral Na/K-ATPase to increase sodium absorption
99
What are the effects of renin release stimulated by the sympathetic nervous system?
Increases angiotensin II
Increases aldosterone
Increases sodium reabsorption
100
What is the main role of ADH?
Control plasma osmolarity
101
What stimulates ADH release?
1% increase in plasma osmolarity
| 10% decrease in blood volume
102
What does ADH act on?
Thick ascending limb to stimulate apical Na/K/Cl co transporter and distal nephron for AQP2 insertion
103
What is the action of atrial natriuretic peptide?
Promote sodium excretion by inhibiting sodium reabsorption along nephron
104
How is ANP stored and released?
Synthesised and stored in atrial myocytes and released proportionally to stretch of these
105
What are low pressure volume sensors?
On low pressure side of circulation e.g. atrial myocytes
106
What are high pressure volume sensors?
Sensors on the atrial side of the circulation system e.g. baroreceptors
107
How does a decrease in effective circulation volume inhibit ANP release?
Decreases heart filling --> decreased stretch --> decreased ANP release
108
What is the effect of ANP on the afferent arteriole?
Causes vasodilation to increase GFR
109
What is the effect of prostaglandins in the kidney?
Locally enhance GFR and decrease sodium reabsorption by increasing blood flow
110
What do prostaglandins act as a buffer to to protect renal blood flow?
Excessive vasoconstriction produced by SNS and RAAS when levels of angiotensin II are raised
111
How can administration of NSAIDs to pts with compromised renal perfusion lead to acute renal failure?
NSAIDs inhibit cyclo-oxygenase pathway so prostaglandins are not synthesised and renal blood flow cannot be protected
112
How is dopamine formed locally in the kidney?
From L-DOPA
113
What is the action of dopamine in the kidney?
Acts on receptors on renal blood vessels, cells of PCT and TAL to cause vasodilation and decreased NaCl reabsorption to buffer against excessive vasoconstriction
114
What action does dopamine have on the transporters of the PCT and TAL?
Inhibits NHE and Na/K/ATPase in principal cells
115
Can the actions of dopamine in the kidney be used therapeutically?
Dopamine agonists are sometimes used as hypertensives
116
What is the numerical classification of mild hypertension?
140-159 (+/-) over 90-99
117
What is the numerical classification of moderate hypertension?
160-179 over 100-109
118
What is the numerical classification of severe hypertension?
>180 over >110
119
What is primary hypertension?
Cause unknown, may be due to genetic/environmental factors
120
What does recent research suggest is the pathogenesis of primary hypertension?
Dysfunction of dopamine agonist
121
What are the causes of secondary hypertension?
Renalvascular disease
Renal parenchymal disease
Adrenal causes
122
How does renalvascular disease cause secondary hypertension?
Renal artery stenosis --> decreased perfusion pressure --> RAAS --> vasoconstriction and sodium retention at the other kidney
123
How does renal parenchymal disease cause secondary hypertension?
Early stage causes loss of vasodilator substances
| Later stage --> inadequate GFR --> sodium and water retention
124
What is Conn's syndrome?
Aldosterone secreting adenoma causing hypertension and hypokalaemia
125
What are the adrenal causes of secondary hypertension?
Conn's syndrome
Cushing's syndrome
Phaeochromocytoma
126
Why does Cushing's syndrome cause secondary hypertension?
Excess cortisol acts on aldosterone receptors
127
How does a phaeochromocytoma cause secondary hypertension?
Catecholamines act on beta-1 in kidney and alpha-1 in vasculature and heart
128
What can arterial damage caused by hypertension lead to?
Atherosclerosis and weakened vessels --> cerbrovascular disease, aneurysm, nephrosclerosis and renal failure, retinopathy
129
What is often the first visible damage due to hypertension?
Retinopathy
130
What effects can increased afterload caused by hypertension have?
Left ventricular hypertrophy --> heart failure
| Increased myocardial afterload --> myocardial ischaemia and MI
131
How is secondary hypertension treated?
Identify and treat underlying cause
132
What methods can be used to treat hypertension?
```
Targeting RAAS
Diuretics
Vasodilators
Beta-blockers
Non-pharmacological approaches
```
133
How can the RAAS be targeted to treat hypertension?
ACE inhibitors
| Angiotensin II antagonists
134
How do diuretics treat hypertension?
Reduce circulation and thus decease cardiac output
135
Give two examples of diuretics that can be used to treat hypertension.
```
Thiazide
Aldosterone antagonists (Spironolactone)
```
136
How do thiazide diuretics treat hypertension?
Act in DCT to inhibit Na/Cl co transporter on apical membrane
137
Are aldosterone antagonists first line treatment for most hypertensive pts?
No
138
How do vasodilators treat hypertension?
Decrease TPR
139
How do L-type calcium channel blockers treat hypertension?
Decrease calcium entry into vascular smooth muscle and hence cause relaxation
140
How do alpha-1-adrenocepetor blockers treat hypertension?
Decrease sympathetic tone thus relaxing vascular smooth muscle
141
How do beta-blockers treat hypertension?
Decrease cardiac output by decreasing HR and contractility
142
Are beta-blockers used as a first line hypertension Tx?
No, only if other indications e.g. previous MI or arrythmia
143
When are non-pharmacological approaches to treating hypertension used exclusively?
Mild hypertension
144
What non-pharmacological approaches can be used to treat hypertension?
```
Exercise
Diet
Decrease sodium intake
Decrease alcohol intake
Stop smoking
```
145
What can limit effectiveness of antihypertensive therapy and lead to more severe hypertension?
Failure to implement lifestyle changes
146
What is the action of aldosterone release from the adrenal cortex?
Activates apical ENaC and K+ channel
| Increases basolateral sodium extrusion via 3Na-2K-ATPase
147
Why does aldosterone increase receptor expression?
It is a steroid hormone
148
What effect does increased levels of sympathetic stimulation in the glomerulus have in longer term BP control?
Causes arteriole vasoconstriction --> decrease GFR --> decrease sodium excretion
149
What is the affect of sympathetic stimulation on the PCT?
Directly activates apical Na/H exchanger and basolateral Na/K-ATPase to increase sodium absorption
150
What are the effects of renin release stimulated by the sympathetic nervous system?
Increases angiotensin II
Increases aldosterone
Increases sodium reabsorption
151
What is the main role of ADH?
Control plasma osmolarity
152
What stimulates ADH release?
1% increase in plasma osmolarity
| 10% decrease in blood volume
153
What does ADH act on?
Thick ascending limb to stimulate apical Na/K/Cl co transporter and distal nephron for AQP2 insertion
154
What is the action of atrial natriuretic peptide?
Promote sodium excretion by inhibiting sodium reabsorption along nephron
155
How is ANP stored and released?
Synthesised and stored in atrial myocytes and released proportionally to stretch of these
156
What are low pressure volume sensors?
On low pressure side of circulation e.g. atrial myocytes
157
What are high pressure volume sensors?
Sensors on the atrial side of the circulation system e.g. baroreceptors
158
How does a decrease in effective circulation volume inhibit ANP release?
Decreases heart filling --> decreased stretch --> decreased ANP release
159
What is the effect of ANP on the afferent arteriole?
Causes vasodilation to increase GFR
160
What is the effect of prostaglandins in the kidney?
Locally enhance GFR and decrease sodium reabsorption by increasing blood flow
161
What do prostaglandins act as a buffer to to protect renal blood flow?
Excessive vasoconstriction produced by SNS and RAAS when levels of angiotensin II are raised
162
How can administration of NSAIDs to pts with compromised renal perfusion lead to acute renal failure?
NSAIDs inhibit cyclo-oxygenase pathway so prostaglandins are not synthesised and renal blood flow cannot be protected
163
How is dopamine formed locally in the kidney?
From L-DOPA
164
What is the action of dopamine in the kidney?
Acts on receptors on renal blood vessels, cells of PCT and TAL to cause vasodilation and decreased NaCl reabsorption to buffer against excessive vasoconstriction
165
What action does dopamine have on the transporters of the PCT and TAL?
Inhibits NHE and Na/K/ATPase in principal cells
166
Can the actions of dopamine in the kidney be used therapeutically?
Dopamine agonists are sometimes used as hypertensives
167
What is the numerical classification of mild hypertension?
140-159 (+/-) over 90-99
168
What is the numerical classification of moderate hypertension?
160-179 over 100-109
169
What is the numerical classification of severe hypertension?
>180 over >110
170
What is primary hypertension?
Cause unknown, may be due to genetic/environmental factors
171
What does recent research suggest is the pathogenesis of primary hypertension?
Dysfunction of dopamine agonist
172
What are the causes of secondary hypertension?
Renalvascular disease
Renal parenchymal disease
Adrenal causes
173
How does renalvascular disease cause secondary hypertension?
Renal artery stenosis --> decreased perfusion pressure --> RAAS --> vasoconstriction and sodium retention at the other kidney
174
How does renal parenchymal disease cause secondary hypertension?
Early stage causes loss of vasodilator substances
| Later stage --> inadequate GFR --> sodium and water retention
175
What is Conn's syndrome?
Aldosterone secreting adenoma causing hypertension and hypokalaemia
176
What are the adrenal causes of secondary hypertension?
Conn's syndrome
Cushing's syndrome
Phaeochromocytoma
177
Why does Cushing's syndrome cause secondary hypertension?
Excess cortisol acts on aldosterone receptors
178
How does a phaeochromocytoma cause secondary hypertension?
Catecholamines act on beta-1 in kidney and alpha-1 in vasculature and heart
179
What can arterial damage caused by hypertension lead to?
Atherosclerosis and weakened vessels --> cerbrovascular disease, aneurysm, nephrosclerosis and renal failure, retinopathy
180
What is often the first visible damage due to hypertension?
Retinopathy
181
What effects can increased afterload caused by hypertension have?
Left ventricular hypertrophy --> heart failure
| Increased myocardial afterload --> myocardial ischaemia and MI
182
How is secondary hypertension treated?
Identify and treat underlying cause
183
What methods can be used to treat hypertension?
```
Targeting RAAS
Diuretics
Vasodilators
Beta-blockers
Non-pharmacological approaches
```
184
How can the RAAS be targeted to treat hypertension?
ACE inhibitors
| Angiotensin II antagonists
185
How do diuretics treat hypertension?
Reduce circulation and thus decease cardiac output
186
Give two examples of diuretics that can be used to treat hypertension.
```
Thiazide
Aldosterone antagonists (Spironolactone)
```
187
How do thiazide diuretics treat hypertension?
Act in DCT to inhibit Na/Cl co transporter on apical membrane
188
Are aldosterone antagonists first line treatment for most hypertensive pts?
No
189
How do vasodilators treat hypertension?
Decrease TPR
190
How do L-type calcium channel blockers treat hypertension?
Decrease calcium entry into vascular smooth muscle and hence cause relaxation
191
How do alpha-1-adrenocepetor blockers treat hypertension?
Decrease sympathetic tone thus relaxing vascular smooth muscle
192
How do beta-blockers treat hypertension?
Decrease cardiac output by decreasing HR and contractility
193
Are beta-blockers used as a first line hypertension Tx?
No, only if other indications e.g. previous MI or arrythmia
194
When are non-pharmacological approaches to treating hypertension used exclusively?
Mild hypertension
195
What non-pharmacological approaches can be used to treat hypertension?
```
Exercise
Diet
Decrease sodium intake
Decrease alcohol intake
Stop smoking
```
196
What can limit effectiveness of antihypertensive therapy and lead to more severe hypertension?
Failure to implement lifestyle changes
