Changes in Plasma Volume and Renal Control of Blood Pressure Flashcards
Where is the water in the body located?
- Intracellular fluid (ICF)
- Extracellular fluid (ECF)
What seperates the intracellular fluid and the extracellular fluid?
The cell membrane
What tightly regulates the volumes of the ICF and ECF?
Their ionic compositions and osmosis
What is ECF volume determined largely by?
The concentration of NaCl
How can the kidney maintain the ECFs volume within a very narrow margin?
By regulating the excretion of NaCl
What must the kidneys balance?
The amount of Na+ excretion with ingestion
What is the process of matching Na+ secretion with ingestion called?
Sodium balance
What is meant by a patient being in positive balance?
Na+ excretion is less than intake
What happens when a patient is in positive balance?
ECF expansion
Why does a positive sodium balance lead to ECF expansion?
Na+ is retained in the body, primarily in the ECF. Water is drawn out of the nephron causing a corresponding increase in volume
What happens as a result of ECF expansion?
With respect to blood volume and arterial pressure
- Blood volume increases
- Arterial pressure increases
Oedema may follow
What is meant by a patient being in negative balance?
Na+ excretion is greater than intake
What happens when a patient is in negative balance?
ECF contraction
Why does a negative sodium balance lead to ECF contraction?
The Na+ content of the ECF decreases, so less water is drawn out of the nephron, so ECF volume decreases
What happens as a result of ECF contraction?
With respect to blood volume and arterial pressure
- Blood volume decreases
- Arterial pressure decreases
Do changes in Na+ affect ECF osmolarity?
No
Why doesn’t changes in Na+ balance affect ECF osmolarity?
If the concentration of Na+ in the ECF increases, then volume increases. The increase in volume gives increased cardiac output, and increased Na+ excretion
What % of Na+ is filtered in the glomerulus?
100%
What % of Na+ is reabsorbed in the PCT?
67%
What is meant by glomerular tubular balance?
The proportion of Na+ reabsorbed is always the same, regardless of the actual amount that is filtered
What does autoregulation do?
Prevents GFR from changing too much
What is the result of glomerular tubular balance?
If any changes in GFR occur, it blunts out the Na+ excretion response
Is Na+ reabsorption an active or passive process?
Mainly active
What drives Na+ reabsorption?
3Na-2K-ATPase pumps on the basolateral membrane
What do different segments of the tubule have?
Different types of Na+ transporters and channels in the apical membrane
Draw a diagram illustrating the different segments of the tubule that have different types of Na+ transporters and channels

What happens in section 1 of the tubule?
- Na+ reabsorption
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
Other than mechanisms to reabsorb Na+, what does section 1 of the tubule have in its membrane?
Aquaporin
What happens to the concentration of urea and Cl- down section 1 of the tubule?
It increases
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
Draw a diagram illustrating Na+-Glucose cotransport in section 1 of the tubule

What happens in sections 2 and 3 of the tubule?
- Na+ and water reabsorption
- Cl- reabsorption
How do sections 2 and 3 of the tubule reabsorp Na+?
Na-H exchanger
How do sections 2 and 3 of the tubule reabsorb water?
Aquaporin
How do sections 2 and 3 of the tubule reabsorb Cl-?
- Paracellular Cl- reabsorption
- Transcellular Cl- reabsorption
Draw a diagram illustrating the processes that occur in sections 2 and 3 of the tubule

What is the overall result of movement of substances in the tubule?
It sets up an ~4mOsmol gradient favouring water uptake from the lumen
How water permeable is the PCT?
Highly
What does the high water permeability of the PCT allow?
Reabsorption to be isosmotic with plasma
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
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
Label this graph illustrating how well substances are reabsorbed

- A - Chloride
- B - Phosphate
- C - HCO3-
- Glucose, AA, and lactate
What is meant by glomerulotubular balance?
The balance between Glomerular Filtration Rate and the rate of reabsorption of solutes
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
How much Na+ is reabsorbed in the PCT?
67%, regardless of GFR
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
What happens to the reabsorption of solute and water in the loop of Henle?
It is separated
What is reabsorbed in the descending limb?
Water, but not NaCl
What is reabsorbed in the ascending limb?
NaCl, but not water
What is the ascending limb known as?
The diluting segment
Why is the ascending limb known as the diluting segment?
Because it dilultes NaCl in the filtrate
How does tubule fluid leaving the loop compared to the plasma?
It is hypo-osmotic (more dilute)
Draw a diagram illustrating the seperation of reabsorption in the loop of Henle

What does the increase in intracellular concentrations of Na+ set up by the PCT allow for?
Paracellular reuptake of water from the descending limb
Are there tight junctions in the descending limb?
No
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
Why does Na+ and Cl- need to concentrate in the lumen of the descending limb?
Ready for active transport into the ascending
Draw a diagram illustrating reuptake in the descending limb

Is the ascending limb permeable to water?
No
Why is the ascending limb impermeable to water?
Tight junctions
Draw a diagram illustrating uptake in the ascending limb

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
What is NaKCC2 a target of?
Loop diuretics
What does increased loss of K+ in the urine lead to?
Hypokalaemia
How does the energy use of the thick ascending limb differ from other regions of the nephron?
It is much higher
What is the TAL particularly sensitive too?
Hypoxia
Draw a diagram illustrating what happens in the TAL

How water permeable is the DCT?
Fairly low
What does the active reabsorption of Na+ in the DCT result in?
Dilution of the filtrate
What enters the distal convoluted tubule from the loop of Henle?
Hypo-osmotic fluid
What happens to the hypo-osmotic fluid in the distal convoluted tubule?
5-8% of its Na+ is actively transported
How is Na+ actively transported in the DCT?
NaCC
What drives NaCC?
3Na-2K-ATPase
What is the NCC transporter sensitive too?
Thiazide diuretics
What is the DCT a major site of?
Calcium reabsorption via PTH
What is the result of dilution in the DCT?
The fluid that leaves is more hypo-osmotic
Draw a diagram illustrating what happens in the DCT

What is the collecting duct?
The region responsible for fine-tuning the filtrate
What is the collecting duct able to do?
Respond to a variety of stimulants
What are the distinct cell types of the collecting duct?
- Principal cells
- Intercalated cells
What % of CD cells are principal cells?
70%
What is the function of principal cells in the CD?
- Reabsorb Na+
- Produces lumen charge
- Variable water uptake
How is Na+ reabsorbed in principal cells?
Epithelial Na+ Channel (ENaC)
What drives ENaC?
3Na-2K-ATPase
What is the importance of the lumen charge produced by principal cells?
Electrical gradient for paracellular Cl- reabsorption
How do principal cells produce the lumen charge?
Potassium secretion into the lumen
How do principal cells take up water?
Aquaporin 2
What is aquaporin 2 dependent on?
ADH
How do principal cells differ from intercalated cells?
They have a more distinct membrane
Draw a diagram illustrating what happens in intercalated cells

What is the function of intercalated cells?
- Active reabsorption of Chloride
- Secrete H+ ions or HCO3-
What is this histograph showing

Collecting ducts
Label this histograph

- A - Intercalated cells
- B - Basement membrane
How many neurohormonal factors control blood pressure?
4
How do the neurohormonal factors controlling blood pressure all work in part?
By controlling sodium balance and ECF volume
What effect does increased Na+ reabsorption have on BP?
Increases it
What are the neurohormonal factors controlling blood pressure?
- Renin-angiotensin-aldosterone system
- Sympathetic nervous system
- Antidiuretic hormone
- Arial Natriuretic peptide
Via what does the sympathetic nervous system exert an effect on blood pressure
- α1-adrenoceptors
- ß1-adrenoceptors
How do α1-adrenoceptors exert an effect on blood pressure?
By causing vasoconstriction
How do ß1-adrenoceptors exert an effect on blood pressure?
It increases the force/rate on heart contraction
What effect does the sympathetic nervous system have on renal blood flow?
Decreases it
What is the result of decreased renal blood flow?
- Decreased GFR and Na+ excretion
- Activates Na/H exchanger in PCT
What effect does the sympathetic nervous system have on renin?
It stimulates its release from juxtaglomerular cells
What is the result of sympathetic nervous system stimulated renin release?
Increased Angiotensin II and aldosterone levels
How does the action of arial natiuretic peptide (ANP) differ from the other neurohormonal factors controlling blood pressure?
It works in the opposite direction
Where is ANP synthesised?
Atrial myocytes
Where is ANP stored?
Atrial myocytes
What does ANP promote?
Na+ excretion
What is the result of Na+ secretion caused by ANP?
Causes vasodilation of afferent arteriole
How does ANP control blood pressure?
- When there is a high BP;
- Atrial cells are stretched
- This leads to increased ANP release
- This leads to increased Na+ excretion
- Volume decreases
- BP decreases
- When there is a low BP;
- Atrial cells are less stretched
- Reduced ANP release
- Volume increases
- BP increases
What is the action of ANP?
Inhibits Na+ reabsorption along the nephron
What detects reduced perfusion pressure in the kidney?
Baroreceptors in the afferent arteriole
What does reduced perfusion pressure in the kidney cause?
The release of renin from the granular cells of the juxtagomerular apparatus
What causes sympathetic stimulation to the JGA?
Decreased NaCl concentration at the Macula Densa cells
What would cause decreased NaCl concentration at the Macula Densa cells?
Due to low perfusion and therefore low GFR
What does sympathetic stimulation to the JGA do?
Increase the release of renin
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
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
- Decreased NaCl concentration at the macula densa
- Sympathetic stimulation to juxtaglomerular appartus
- Decreased renal perfusion pressure (sensed by renal baroreceptors)
What does renin do?
Cleaves angiotensinogen to angiotensin I
What happens to angiotensin I?
It is cleaved to form the active hormone Angiotensin II
What cleaves angiotensin I to angiotensin II?
Angiotensin converting enzyme (ACE)
Draw a diagram illustrating the renin-angiotensin system

What are the types of angiotensin II receptors?
- AT1
- AT2
What kind of receptors are the angiotensin II receptors?
G-protein coupled receptors
What receptor is the main action of angiotensin II via?
The AT1 receptor
What sites does angiotensin II act at?
- Arterioles
- Kidney
- Sympathetic NS
- Adrenal cortex
- Hypothalamus
What is the action of angiotensin II at the arterioles?
Vasoconstriction
What is the action of angiotensin II at the kidney?
Stimulates Na+ reabsorption at the kidney
What is the action of angiotensin II on the sympathetic nervous system?
Increased release of NA
What is the action of angiotensin II at the adrenal cortex?
Stimulates release of aldosterone
What is the action of angiotensin II on the hypothalamus?
Increases thirst sensation
How does angiotensin II increase thirst sensation?
Stimulates ADH release
What are the actions of angiotensin II?
- Vasoconstriction
- Aldosterone release
- Sympathetic activity
- Increased Na+ reabsorption
- Thirst
- Breaks down bradykinin
In what cells does angiotensin II cause vasoconstriction?
Vascular smooth muscle
What is the effect of angiotensin II induced vasoconstriction?
Increasess TPR and therefore BP
Where does angiotensin II cause vasoconstriction?
In the afferent and efferent arteriole
How does angiotensin II stimulate the release of aldosterone?
It stimulates the adrenal cortex to synthesise and release aldosterone
What does aldosterone do?
- Stimulates Na+ and therefore water reabsorption
- Activates ENaC and apical K+ channels
- Increases basolateral Na+ extrusion
How does aldosterone increase basolateral Na+ extrusion?
Via 3Na-2K-ATPase
What does aldosterone act on?
Principal cells of CD
How does aldosterone increase Na+ reabsorption?
Stimulates Na-H exchanger in the apical membrane of PCT
What is bradykinin?
A vasodilatory
Draw a diagram illustrating the action of aldosterone

What does the baroreceptor reflex work to do?
Control acute changes in BP
On what time scale does the baroreceptor reflex work?
Produces a rapid response, but does not control sustained increases
Why does the baroreceptor reflex not control sustained increases in blood pressure?
As the threshold for baroreceptor firing resets
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
How do low-pressure baroreceptors in the atria and pulmonary vasculature sendd signals to the brainstem?
Via the vagus nerve
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
What does a 5-150% change in blood pressure cause?
High-pressure baroreceptors to send impulses
Where are high-pressure baroreceptors located?
In the carotid sinus and aortic arch
What do high-pressure baroreceptors send impulses via?
The vagus and glossopharyngeal nerves
What is the effect of a decrease in blood pressure?
- Increase sympathetic nerve activity
- Increase secretion of ADH
What are the actions of ADH?
- Addition of aquaporin to the collecting duct
- Stimulates apical Na/K/Cl co-transporter
What is the purpose of the addition of aquaporin to the collecting duct?
Allows the reabsorption of water
What is the result of the reabsorption of water through aquaporin?
It forms concentrated urine
What is the release of ADH stimulated by?
- Increases in plasma osmolarity
- Severe hypovolemia
Where does ADH stimulate the apical Na/K/Cl co-transporter?
In the thick ascending limb
What is the result of ADH stimulation of apical Na/K/Cl co-transporter?
Less Na+ moves out into the medulla
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
What are prostaglandins?
Vasodilators
What do locally acting prostaglandins do?
- Enhance glomerular filtration
- Reduce Na+ reabsorption
What is the main locally acting prostaglandin?
PGE2
What important protective function do prostaglandins have?
Act as a buffer to excessive vasoconstriction by the sympathetic nervous system and the RAAS
What do non-steroidal anti-inflammatory drugs (NSAIDs) do?
Inhibit the cyclo-oxygenase (COX) pathway
What is the COX pathway involved in?
The formation of prostaglandins
When should NSAIDs not be administered?
When renal perfusion is compromised
Give an example of when renal perfusion may be compromised
In renal disease
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
What can happen if NSAIDs are given to patients in heart failure or with hypertension?
They can exacerbate the condition
Why can NSAIDs exacerbate heart failure or hypertension?
Because they can increase NaCl and water retention
What is hypertension?
A sustained increase in blood pressure
What is essential hypertension?
Hypertension when the cause is unknown
What % of hypertension cases are essential hypertension?
95%
What factors may be involved in essential hypertension?
- Genetic
- Environmental
What is secondary hypertension?
Hypertension where a cause can be defined
What is important in secondary hypertension?
To treat the primary cause
Give 4 diseases that can give rise to secondary hypertension
- Renovascular disease
- Chronic renal diseease
- Aldosteronism
- Cushing’s syndrome
What is classified as mild hypertension?
140-159mmHg systolic/90-99mmHg diastolic
What is classified as moderate hypertension?
160-179mmHg systolic/100-109mmHg diastolic
What is classified as severe hypertension?
>180mmHg systolic/>110mmHg diastolic
What is renovascular disease caused by?
An occlusion of the renal artery
What does an occlusion of the renal artery cause?
A fall in perfusion pressure in that kidney
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
What are the adrenal causes of hypertension?
- Conn’s Syndrome
- Cushing’s Syndrome
- Pheochromocytoma
What is Conn’s Syndrome?
An aldosterone secreting adenoma
What does Conn’s syndrome cause?
Hypertension and hypokalaemia
What is Cushing’s syndrome?
Excess cortisol
How does Cushing’s syndrome cause hypertension?
At high concentrations, cortisol acts on aldosterone receptors, causing Na+ and water retention
What is a pheochromocytoma?
Tumour of the adrenal medulla
What does a pheochromocytoma secrete?
- Noradrenaline
- Adrenaline
How is hypertension treated?
- ACE inhibitors
- Thiazide Diuretics
- Vasodilators
- Beta blockers
What are ACE inhibitors?
Angiotensin II receptor antagonists
What is ACE inhibitors mechanism of action?
They prevent the production of Angiotensin II from Angiotensin I
What do thiazide diuretics do?
Inhibit NaCC co-transporter on apical membrane of DCT
What may thiazide diuretics cause?
Hypokalaemia
Why may thiazide diuretics cause hypokalaemia?
More K+ lost in urine
What are the types of vasodilators used in the treatment of hypertension?
- Ca2+ channel blockers
- α1 channel blockers
What do Ca2+ channel blocks do?
Reduce Ca2+ entry into smooth muscle cells
What do α1 receptor blockers do?
Reduce sympathetic tone
What do beta blockers act on?
ß1-receptors in the heart
What do beta blockers do?
Reduce heart rate and contractility
What are the non-pharmacological approaches to the treatment of hypertension?
- Diet
- Exercise
- Reduced sodium intake
- Reduced alcohol intake