Changes in Plasma Volume and Renal Control of Blood Pressure Flashcards
(204 cards)
1
Q
Where is the water in the body located?
A
- Intracellular fluid (ICF)
- Extracellular fluid (ECF)
2
Q
What seperates the intracellular fluid and the extracellular fluid?
A
The cell membrane
3
Q
What tightly regulates the volumes of the ICF and ECF?
A
Their ionic compositions and osmosis
4
Q
What is ECF volume determined largely by?
A
The concentration of NaCl
5
Q
How can the kidney maintain the ECFs volume within a very narrow margin?
A
By regulating the excretion of NaCl
6
Q
What must the kidneys balance?
A
The amount of Na+ excretion with ingestion
7
Q
What is the process of matching Na+ secretion with ingestion called?
A
Sodium balance
8
Q
What is meant by a patient being in positive balance?
A
Na+ excretion is less than intake
9
Q
What happens when a patient is in positive balance?
A
ECF expansion
10
Q
Why does a positive sodium balance lead to ECF expansion?
A
Na+ is retained in the body, primarily in the ECF. Water is drawn out of the nephron causing a corresponding increase in volume
11
Q
What happens as a result of ECF expansion?
With respect to blood volume and arterial pressure
A
- Blood volume increases
- Arterial pressure increases
Oedema may follow
12
Q
What is meant by a patient being in negative balance?
A
Na+ excretion is greater than intake
13
Q
What happens when a patient is in negative balance?
A
ECF contraction
14
Q
Why does a negative sodium balance lead to ECF contraction?
A
The Na+ content of the ECF decreases, so less water is drawn out of the nephron, so ECF volume decreases
15
Q
What happens as a result of ECF contraction?
With respect to blood volume and arterial pressure
A
- Blood volume decreases
- Arterial pressure decreases
16
Q
Do changes in Na+ affect ECF osmolarity?
A
No
17
Q
Why doesn’t changes in Na+ balance affect ECF osmolarity?
A
If the concentration of Na+ in the ECF increases, then volume increases. The increase in volume gives increased cardiac output, and increased Na+ excretion
18
Q
What % of Na+ is filtered in the glomerulus?
A
100%
19
Q
What % of Na+ is reabsorbed in the PCT?
A
67%
20
Q
What is meant by glomerular tubular balance?
A
The proportion of Na+ reabsorbed is always the same, regardless of the actual amount that is filtered
21
Q
What does autoregulation do?
A
Prevents GFR from changing too much
22
Q
What is the result of glomerular tubular balance?
A
If any changes in GFR occur, it blunts out the Na+ excretion response
23
Q
Is Na+ reabsorption an active or passive process?
A
Mainly active
24
Q
What drives Na+ reabsorption?
A
3Na-2K-ATPase pumps on the basolateral membrane
25
What do different segments of the tubule have?
Different types of Na+ transporters and channels in the apical membrane
26
Draw a diagram illustrating the different segments of the tubule that have different types of Na+ transporters and channels
27
What happens in section 1 of the tubule?
* Na+ reabsorption
28
How does Na+ reabsorption occur in section 1 of the tubule?
* Co-transported with glucose
* Na-H exchange
* Co-transport with AA or carboxylic acids
* Co-transport with phosphate
29
Other than mechanisms to reabsorb Na+, what does section 1 of the tubule have in its membrane?
Aquaporin
30
What happens to the concentration of urea and Cl- down section 1 of the tubule?
It increases
31
What is the purpose of the increase in Cl- concentration down section 1 of the tubule?
It increases the concentration gradient for Cl- reabsorption in sections 2 and 3
32
Draw a diagram illustrating Na+-Glucose cotransport in section 1 of the tubule
33
What happens in sections 2 and 3 of the tubule?
* Na+ and water reabsorption
* Cl- reabsorption
34
How do sections 2 and 3 of the tubule reabsorp Na+?
Na-H exchanger
35
How do sections 2 and 3 of the tubule reabsorb water?
Aquaporin
36
How do sections 2 and 3 of the tubule reabsorb Cl-?
* Paracellular Cl- reabsorption
* Transcellular Cl- reabsorption
37
Draw a diagram illustrating the processes that occur in sections 2 and 3 of the tubule
38
What is the overall result of movement of substances in the tubule?
It sets up an ~4mOsmol gradient favouring water uptake from the lumen
39
How water permeable is the PCT?
Highly
40
What does the high water permeability of the PCT allow?
Reabsorption to be isosmotic with plasma
41
What is the reabsorption of water in the PCT driven by?
* Osmotic gradient established by solute reabsorption
* Hydrostatic force in the intersticium
* Oncotic force in the peritubular capillary
42
What produces the oncotic force in the peritubular capillary?
The loss of 20% filtrate at the glomerulus, but cells and proteins remained in the blood
43
Label this graph illustrating how well substances are reabsorbed
* A - Chloride
* B - Phosphate
* C - HCO3-
* Glucose, AA, and lactate
44
What is meant by glomerulotubular balance?
The balance between Glomerular Filtration Rate and the rate of reabsorption of solutes
45
What must be true of the glomerulotubular balance?
It must be kept as constant as possible, *so if GFR increases, the rate of reabsorption must also increase*
46
How much Na+ is reabsorbed in the PCT?
67%, *regardless of GFR*
47
How does an ECF volume increase cause an increase in GFR?
If ECF volume increases, cardiac output will increase, causing an increase in arterial blood pressure, which in turn will increase GFR
48
What happens to the reabsorption of solute and water in the loop of Henle?
It is separated
49
What is reabsorbed in the descending limb?
Water, *but not NaCl*
50
What is reabsorbed in the ascending limb?
NaCl, *but not water*
51
What is the ascending limb known as?
The diluting segment
52
Why is the ascending limb known as the diluting segment?
Because it dilultes NaCl in the filtrate
53
How does tubule fluid leaving the loop compared to the plasma?
It is hypo-osmotic *(more dilute)*
54
Draw a diagram illustrating the seperation of reabsorption in the loop of Henle
55
What does the increase in intracellular concentrations of Na+ set up by the PCT allow for?
Paracellular reuptake of water from the descending limb
56
Are there tight junctions in the descending limb?
No
57
What is the result of the paracellular reuptake of water from the descending limb?
It concentrates Na+ and Cl- in the lumen of the descending
58
Why does Na+ and Cl- need to concentrate in the lumen of the descending limb?
Ready for active transport into the ascending
59
Draw a diagram illustrating reuptake in the descending limb
60
Is the ascending limb permeable to water?
No
61
Why is the ascending limb impermeable to water?
Tight junctions
62
Draw a diagram illustrating uptake in the ascending limb
63
What happens in the thick ascending limb (TAL)?
* NaCl is transported from the lumen into cells by NaKCC2 channel
* Na+ then moves into the intersticium due to the action of 3Na-2K-ATPase
* K+ ions diffuse back into the lumen via ROMK
* Cl- ions move into the Intersticium
64
What is NaKCC2 a target of?
Loop diuretics
65
What does increased loss of K+ in the urine lead to?
Hypokalaemia
66
How does the energy use of the thick ascending limb differ from other regions of the nephron?
It is much higher
67
What is the TAL particularly sensitive too?
Hypoxia
68
Draw a diagram illustrating what happens in the TAL
69
How water permeable is the DCT?
Fairly low
70
What does the active reabsorption of Na+ in the DCT result in?
Dilution of the filtrate
71
What enters the distal convoluted tubule from the loop of Henle?
Hypo-osmotic fluid
72
What happens to the hypo-osmotic fluid in the distal convoluted tubule?
5-8% of its Na+ is actively transported
73
How is Na+ actively transported in the DCT?
NaCC
74
What drives NaCC?
3Na-2K-ATPase
75
What is the NCC transporter sensitive too?
Thiazide diuretics
76
What is the DCT a major site of?
Calcium reabsorption via PTH
77
What is the result of dilution in the DCT?
The fluid that leaves is more hypo-osmotic
78
Draw a diagram illustrating what happens in the DCT
79
What is the collecting duct?
The region responsible for fine-tuning the filtrate
80
What is the collecting duct able to do?
Respond to a variety of stimulants
81
What are the distinct cell types of the collecting duct?
* Principal cells
* Intercalated cells
82
What % of CD cells are principal cells?
70%
83
What is the function of principal cells in the CD?
* Reabsorb Na+
* Produces lumen charge
* Variable water uptake
84
How is Na+ reabsorbed in principal cells?
Epithelial Na+ Channel (ENaC)
85
What drives ENaC?
3Na-2K-ATPase
86
What is the importance of the lumen charge produced by principal cells?
Electrical gradient for paracellular Cl- reabsorption
87
How do principal cells produce the lumen charge?
Potassium secretion into the lumen
88
How do principal cells take up water?
Aquaporin 2
89
What is aquaporin 2 dependent on?
ADH
90
How do principal cells differ from intercalated cells?
They have a more distinct membrane
91
Draw a diagram illustrating what happens in intercalated cells
92
What is the function of intercalated cells?
* Active reabsorption of Chloride
* Secrete H+ ions or HCO3-
93
What is this histograph showing
Collecting ducts
94
Label this histograph
* A - Intercalated cells
* B - Basement membrane
95
How many neurohormonal factors control blood pressure?
4
96
How do the neurohormonal factors controlling blood pressure all work in part?
By controlling sodium balance and ECF volume
97
What effect does increased Na+ reabsorption have on BP?
Increases it
98
What are the neurohormonal factors controlling blood pressure?
* Renin-angiotensin-aldosterone system
* Sympathetic nervous system
* Antidiuretic hormone
* Arial Natriuretic peptide
99
Via what does the sympathetic nervous system exert an effect on blood pressure
* α1-adrenoceptors
* ß1-adrenoceptors
100
How do α1-adrenoceptors exert an effect on blood pressure?
By causing vasoconstriction
101
How do ß1-adrenoceptors exert an effect on blood pressure?
It increases the force/rate on heart contraction
102
What effect does the sympathetic nervous system have on renal blood flow?
Decreases it
103
What is the result of decreased renal blood flow?
* Decreased GFR and Na+ excretion
* Activates Na/H exchanger in PCT
104
What effect does the sympathetic nervous system have on renin?
It stimulates its release from juxtaglomerular cells
105
What is the result of sympathetic nervous system stimulated renin release?
Increased Angiotensin II and aldosterone levels
106
How does the action of arial natiuretic peptide (ANP) differ from the other neurohormonal factors controlling blood pressure?
It works in the opposite direction
107
Where is ANP synthesised?
Atrial myocytes
108
Where is ANP stored?
Atrial myocytes
109
What does ANP promote?
Na+ excretion
110
What is the result of Na+ secretion caused by ANP?
Causes vasodilation of afferent arteriole
111
How does ANP control blood pressure?
* When there is a high BP;
1. Atrial cells are stretched
2. This leads to increased ANP release
3. This leads to increased Na+ excretion
4. Volume decreases
5. BP decreases
* When there is a low BP;
1. Atrial cells are less stretched
2. Reduced ANP release
3. Volume increases
4. BP increases
112
What is the action of ANP?
Inhibits Na+ reabsorption along the nephron
113
What detects reduced perfusion pressure in the kidney?
Baroreceptors in the afferent arteriole
114
What does reduced perfusion pressure in the kidney cause?
The release of renin from the granular cells of the juxtagomerular apparatus
115
What causes sympathetic stimulation to the JGA?
Decreased NaCl concentration at the Macula Densa cells
116
What would cause decreased NaCl concentration at the Macula Densa cells?
Due to low perfusion and therefore low GFR
117
What does sympathetic stimulation to the JGA do?
Increase the release of renin
118
Other than sympathetic stimulation, what does decreased NaCl concentration at the Macula Densa cells cause?
The Macula Densa cells to release prostaglandins, and so cause afferent vasodilation
119
Label this diagram and show how it relates to the regulation of blood pressure
* A - Afferent arteriole
* B - Granular cells or juxtaglomerular cells
* C - Distal tubule
* D - Macula densa
* E - Efferent arteriole
* F - Glomerular capillaries
* G - Proximal tubule
* H - Intraglomerular mesangial cells
* I - Bowman's space
* J - Podocyte
* K - Extraglomerular mesangial cells
1. Decreased NaCl concentration at the macula densa
2. Sympathetic stimulation to juxtaglomerular appartus
3. Decreased renal perfusion pressure *(sensed by renal baroreceptors)*
120
What does renin do?
Cleaves angiotensinogen to angiotensin I
121
What happens to angiotensin I?
It is cleaved to form the active hormone Angiotensin II
122
What cleaves angiotensin I to angiotensin II?
Angiotensin converting enzyme (ACE)
123
Draw a diagram illustrating the renin-angiotensin system
124
What are the types of angiotensin II receptors?
* AT1
* AT2
125
What kind of receptors are the angiotensin II receptors?
G-protein coupled receptors
126
What receptor is the main action of angiotensin II via?
The AT1 receptor
127
What sites does angiotensin II act at?
* Arterioles
* Kidney
* Sympathetic NS
* Adrenal cortex
* Hypothalamus
128
What is the action of angiotensin II at the arterioles?
Vasoconstriction
129
What is the action of angiotensin II at the kidney?
Stimulates Na+ reabsorption at the kidney
130
What is the action of angiotensin II on the sympathetic nervous system?
Increased release of NA
131
What is the action of angiotensin II at the adrenal cortex?
Stimulates release of aldosterone
132
What is the action of angiotensin II on the hypothalamus?
Increases thirst sensation
133
How does angiotensin II increase thirst sensation?
Stimulates ADH release
134
What are the actions of angiotensin II?
* Vasoconstriction
* Aldosterone release
* Sympathetic activity
* Increased Na+ reabsorption
* Thirst
* Breaks down bradykinin
135
In what cells does angiotensin II cause vasoconstriction?
Vascular smooth muscle
136
What is the effect of angiotensin II induced vasoconstriction?
Increasess TPR and therefore BP
137
Where does angiotensin II cause vasoconstriction?
In the afferent and efferent arteriole
138
How does angiotensin II stimulate the release of aldosterone?
It stimulates the adrenal cortex to synthesise and release aldosterone
139
What does aldosterone do?
* Stimulates Na+ and therefore water reabsorption
* Activates ENaC and apical K+ channels
* Increases basolateral Na+ extrusion
140
How does aldosterone increase basolateral Na+ extrusion?
Via 3Na-2K-ATPase
141
What does aldosterone act on?
Principal cells of CD
142
How does aldosterone increase Na+ reabsorption?
Stimulates Na-H exchanger in the apical membrane of PCT
143
What is bradykinin?
A vasodilatory
144
Draw a diagram illustrating the action of aldosterone
145
What does the baroreceptor reflex work to do?
Control acute changes in BP
146
On what time scale does the baroreceptor reflex work?
Produces a rapid response, but does not control sustained increases
147
Why does the baroreceptor reflex not control sustained increases in blood pressure?
As the threshold for baroreceptor firing resets
148
What does a 5-10% drop in blood pressure cause?
Low-pressure baroreceptors in the atria and pulmonary vasculature to send signals to the brainstem
149
How do low-pressure baroreceptors in the atria and pulmonary vasculature sendd signals to the brainstem?
Via the vagus nerve
150
What do the signals sent to the brainstem from the low-pressure baroreceptors in the atria and pulmonary vasculature do?
Modulate both sympathetic nerve outflow, secretion of the hormone ADH, and reduction of ANP release
151
What does a 5-150% change in blood pressure cause?
High-pressure baroreceptors to send impulses
152
Where are high-pressure baroreceptors located?
In the carotid sinus and aortic arch
153
What do high-pressure baroreceptors send impulses via?
The vagus and glossopharyngeal nerves
154
What is the effect of a decrease in blood pressure?
* Increase sympathetic nerve activity
* Increase secretion of ADH
155
What are the actions of ADH?
* Addition of aquaporin to the collecting duct
* Stimulates apical Na/K/Cl co-transporter
156
What is the purpose of the addition of aquaporin to the collecting duct?
Allows the reabsorption of water
157
What is the result of the reabsorption of water through aquaporin?
It forms concentrated urine
158
What is the release of ADH stimulated by?
* Increases in plasma osmolarity
* Severe hypovolemia
159
Where does ADH stimulate the apical Na/K/Cl co-transporter?
In the thick ascending limb
160
What is the result of ADH stimulation of apical Na/K/Cl co-transporter?
Less Na+ moves out into the medulla
161
What is the result of less Na+ moving out into the medulla?
Reduces the osmotic gradient for water to exit the lumen into the peritubular capillaries from the thin descending limb
162
What are prostaglandins?
Vasodilators
163
What do locally acting prostaglandins do?
* Enhance glomerular filtration
* Reduce Na+ reabsorption
164
What is the main locally acting prostaglandin?
PGE2
165
What important protective function do prostaglandins have?
Act as a buffer to excessive vasoconstriction by the sympathetic nervous system and the RAAS
166
What do non-steroidal anti-inflammatory drugs (NSAIDs) do?
Inhibit the cyclo-oxygenase (COX) pathway
167
What is the COX pathway involved in?
The formation of prostaglandins
168
When should NSAIDs not be administered?
When renal perfusion is compromised
169
Give an example of when renal perfusion may be compromised
In renal disease
170
Why should NSAIDs not be administed when renal perfusion is compromised?
As prostaglandins help maintain renal blood flow and GFR in the presence of vasoconstrictors, if NSAIDs are administered, the GFR is further decreased, leading to acute renal failure
171
What can happen if NSAIDs are given to patients in heart failure or with hypertension?
They can exacerbate the condition
172
Why can NSAIDs exacerbate heart failure or hypertension?
Because they can increase NaCl and water retention
173
What is hypertension?
A sustained increase in blood pressure
174
What is essential hypertension?
Hypertension when the cause is unknown
175
What % of hypertension cases are essential hypertension?
95%
176
What factors may be involved in essential hypertension?
* Genetic
* Environmental
177
What is secondary hypertension?
Hypertension where a cause can be defined
178
What is important in secondary hypertension?
To treat the primary cause
179
Give 4 diseases that can give rise to secondary hypertension
* Renovascular disease
* Chronic renal diseease
* Aldosteronism
* Cushing's syndrome
180
What is classified as mild hypertension?
140-159mmHg systolic/90-99mmHg diastolic
181
What is classified as moderate hypertension?
160-179mmHg systolic/100-109mmHg diastolic
182
What is classified as severe hypertension?
\>180mmHg systolic/\>110mmHg diastolic
183
What is renovascular disease caused by?
An occlusion of the renal artery
184
What does an occlusion of the renal artery cause?
A fall in perfusion pressure in that kidney
185
What does decreased perfusion of the kidney lead to?
* That kidney releasing renin and activating RAAS
* Vasoconstriction and Na+ retention will then take place at the other kidney
186
What are the adrenal causes of hypertension?
* Conn's Syndrome
* Cushing's Syndrome
* Pheochromocytoma
187
What is Conn's Syndrome?
An aldosterone secreting adenoma
188
What does Conn's syndrome cause?
Hypertension and hypokalaemia
189
What is Cushing's syndrome?
Excess cortisol
190
How does Cushing's syndrome cause hypertension?
At high concentrations, cortisol acts on aldosterone receptors, causing Na+ and water retention
191
What is a pheochromocytoma?
Tumour of the adrenal medulla
192
What does a pheochromocytoma secrete?
* Noradrenaline
* Adrenaline
193
How is hypertension treated?
* ACE inhibitors
* Thiazide Diuretics
* Vasodilators
* Beta blockers
194
What are ACE inhibitors?
Angiotensin II receptor antagonists
195
What is ACE inhibitors mechanism of action?
They prevent the production of Angiotensin II from Angiotensin I
196
What do thiazide diuretics do?
Inhibit NaCC co-transporter on apical membrane of DCT
197
What may thiazide diuretics cause?
Hypokalaemia
198
Why may thiazide diuretics cause hypokalaemia?
More K+ lost in urine
199
What are the types of vasodilators used in the treatment of hypertension?
* Ca2+ channel blockers
* α1 channel blockers
200
What do Ca2+ channel blocks do?
Reduce Ca2+ entry into smooth muscle cells
201
What do α1 receptor blockers do?
Reduce sympathetic tone
202
What do beta blockers act on?
ß1-receptors in the heart
203
What do beta blockers do?
Reduce heart rate and contractility
204
What are the non-pharmacological approaches to the treatment of hypertension?
* Diet
* Exercise
* Reduced sodium intake
* Reduced alcohol intake
