Session 4

Question 1

Describe the fluid compartments in the body and their electrolyte compositions

Answer 1

[*] 2 compartments in the body: ICF and ECF, separated by the cell membrane.

[*] The kidneys are crucial in maintaining both volume and composition of the fluid; this homeostatic maintenance of plasma volume occurs despite varying inputs i.e. drinking lots or being dehydrated, throughout the day.

[*] The ECF volume, which includes the vascular system is determined largely by the concentration of NaCl in this compartment. By regulating the excretion of NaCl, the kidney maintains the volume of the ECF within a very narrow margin.

[*] In the ICF the predominant cation is K+ and in ECF, the predominant cation is Na+

Question 2

Explain about Sodium Balance

Answer 2

[*] Sodium is the major cation of the ECF and the amount of sodium ions determines the ECF volume (movement of water follows movement of Na+) => determining the volume of plasma, blood volume and hence blood pressure.

[*] On a daily basis, the kidneys must balance the amount of sodium ion excretion so it matches the amount of sodium ion ingestion – this matching process is known as sodium ion balance.

• This avoids the blood pressure changing due to variation of Na+ intake in diet
• Urinary water excretion can be varied physiologically.

[*] Expansion of the ECF: if sodium ion excretion is less than intake then a patient is in positive balance. In this case, extra Na+ ions are retained in the body primarily in the ECF. When the sodium ion content of the ECF increases there is a corresponding increase in ECF volume as water from the nephron is drawn out blood volume and arterial pressure increase and oedema may follow.

Question 3

Explain about expansion and contraction of the ECF

Answer 3

• Expansion of the ECF: if sodium ion excretion is less than intake then a patient is in positive balance. In this case, extra Na+ ions are retained in the body primarily in the ECF. When the sodium ion content of the ECF increases there is a corresponding increase in ECF volume as water from the nephron is drawn out blood volume and arterial pressure increase and oedema may follow.
• [*] Contraction of the ECF: if sodium ion excretion is greater than ingestion, then a patient is in negative balance. Excess Na+ ions are lost from the body, the Na+ content of the ECF decreases and water remains in the nephron. The ECF volume decreases as does blood volume and arterial pressure.
• [*] NB: we are talking about the total amount of sodium ions not the concentration of the sodium; (you could have a low or high concentration of Na+ depending on the volume of water without affecting the overall Na+ ion amount).
• [*] Changes in sodium ion balance does not affect ECF osmolarity; if the concentration of Na+ ions in the ECF increases the volume increases. This volume expansion results in increased vascular volume and cardiac output. The increase in volume would trigger an increased sodium ion excretion (natriuresis).

Question 4

Explain about the handling of Sodium ions in the PCT

Answer 4

[*] 100% of Na+ is filtered in the glomerulus, and 67% is reabsorbed in the PCT

[*] This is a proportion of Na+ that is always reabsorbed regardless of the actual amount that is filtered. Autoregulation prevents the glomerular filtration rate from changing too much but if any changes occur despite this, Glomerular Tubular Balance blunts the Na+ excretion response

[*] Na+ reabsorption is mainly active, driven by the 3Na-2K-ATPase basolateral membrane. Different segments of the tubule have different types of Na+ transporters and channels in the apical (luminal) membrane

• Sodium reabsorption is a transcellular process
• Chloride reabsorption is by transcellular (active) and some paracellular (passive) – coupled to 3Na-2K-ATPase pumps.
• Na+ ion reabsorption (chloride is implied)

Question 5

Describe Chloride reabsorption

Answer 5

• Dependent on sodium reabsorption
• Important to remain electro-neutrality – a finite volume of filtrate must contain equal amounts of anions and cations
• 1 litre of filtrate contains: ~145mM Na+, ~110mM Cl- and ~24mM HCO3-
• PCT reabsorption cations and anions must balance: Na+ = (Cl- + HCO3-)
• HCO3- (90%) is reabsorbed in PCT
• Cl- in PCT reabsorbed ~60%

Question 6

Explain about reabsorption in S1 of the PCT

Answer 6

Basolateral: 3Na-2K-ATPAse and NAHCO3- co transporter
Apical:

• Co-transported with glucose
• Na-H exchange
• Co-transport with amino acids / carboxylic acids
• Co-transport with phosphate (increased [PTH])
• Aquaporin (water can move through)
• Increased [Urea/Cl-] down S1 compensating for loss of glucose etc creates a concentration gradient for Cl- passive reabsorption in S2/S3

Question 7

Explain about reabsorption in S2/S3 of the PCT

Answer 7

Section 2/3: Na+ and Water Reabsorption

Basolateral 3Na-2K-ATPase

Luminal Na reabsorbed in S2/S3 via Na-H exchanger
Apical membrane has:

• Na-H exchanger
• Paraceullar Cl- reabsorption
• Transcellular Cl- reabsorption
• Aquaporin
• This sets up an ~4mOsmol gradient favouring water uptake from the lumen

Question 8

Describe isosmotic reabsorption in the PCT

Answer 8

PCT is highly water permeable which allows reabsorption to be isosmotic with plasma
The reabsorption of water is driven by:

• Osmotic gradient established by solute reabsorption
• Hydrostatic force in Intersticium
• Oncotic force in the peritubular capillary due to the loss of 20% filtrate at the glomerulus, but cells and proteins remained in the blood

In the PCT, there is fast preferential absorption for glucose, amino acids and lactate but Cl- reabsorption lags behind (maintaining osmolarity in the filtrate in the lumen) so osmolarity stays constant despite the solute reabsorption

[*] PCT reabsorption into peritubular capillary

• Proximal tubule highly water permeable
• Tight junctions between tubular cells form a barrier that prevents diffusion of transporter, channel and pump proteins between the apical and basolateral membrane. They maintain the polarity of the tubule cells.
• A bulk transport or obligatory water reabsorption
• PCT reabsorbs 65% of water, 100% of glucose and AA, and 67% of NA

Question 9

What is the Glomerulotubular Balance?

Answer 9

[*] Autoregulation of GFR prevents GFR from changing too much via myogenic action and tubule-glomerular feedback.

[*] [Glomerulotubular balance is the balance between GFR and the rate of reabsorption of solutes. It must be kept as constant as possible, so if GFR increases, the rate of reabsorption must also increase.

[*] If ECF volume increases, cardiac output will increase causing an increase in arterial blood pressure. This will in turn increase GFR.

[*] 2nd line of defence is the Glomerulotubular response which blunts Na+ excretion response to any GFR changes which do occur despite autoregulation

Question 10

Describe reabsorption in the loop of Henle (overall)

Answer 10

[*] In the loop of Henle, the reabsorption of solute and water is separated: descending limb reabsorbs water but not NaCl and ascending limb absorbs NaCl but not water.

• The loop of Henle is known as diluting segment as NaCl is diluted in the filtrate.
• Tubule fluid leaving the loop is therefore hypo-osmotic (more dilute) compared to plasma

Question 11

Describe reabsorption in the Descending Limb

Answer 11

[*] Thin and Thick Descending Limb

The increase in intracellular concentrations of Na+ set up by the PCT allows for the paracellular reuptake of water from the descending limb (NO TIGHT JUNCTIONS).
This concentrates the Na+ and Cl- in the filtrate in the lumen of the descending limb, ready for active transport in the ascending. Chicken and egg who came first?

Question 12

Describe reabsorption in the Ascending limb

Answer 12

[*] Ascending Limb: IMPERMEABLE to water (tight junctions)

Thin ascending limb: not much active transport occurs

• Sodium reabsorption is passive
• Water reabsorption in descending limb creates a gradient for passive Na+ ion reabsorption in thin ascending limb
• Epithelium in thin ascending limb permits reabsorption by paraceullar route (between the epithelial cells) – there are loose junctions unlike in the thick ascending limb

Thick Ascending Limb (TAL):

• NaCl transported from the lumen into tubule 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 (normally ROMK is on the basolateral membrane but here it is on the apical membrane to allow for K+ secretion)
• Cl- ions move into the Intersticium
• In the filtrate in the lumen at this point, there is less K+ ions so in order to maintain activity of the NaKCC2 transporter its vital the K+ ions diffuse back into the filtrate.
• NaKCC2 is the target of loop diuretics (leads to reduced blood volume as increased water excretion however also leads to increased loss of K+ in the urine => hypokalaemia)

The Thick Ascending Limb uses more energy than any other region of the nephron, and is particularly sensitive to hypoxia

Question 13

Describe Sodium Uptake in the early Distal Tubule

Answer 13

[*] Distal Convoluted Tubule: water permeability of the early DCT is fairly low and the active reabsorption of Na+ results in dilution of the filtrate (inside the tubular cell)

• Hypo-osmotic fluid enters from the lop of Henle and ~5.8% of Na+ is actively transported by the NaCC transporter, driven by 3Na-2K-ATPase
• The NCC transporter is sensitive to Thiazide Diuretics
• The DCT is a major site of calcium reabsorption via PTH.
• This FURTHER DILUTION means the fluid that leaves is more hypo-osmotic

Question 14

Describe reabsorption in the late DCT and Collecting Duct

Answer 14

In the late DCT and collecting duct, water permeability is variable depending on ADH. Collecting Duct is the region responsible for fine tuning the filtrate. Tubular epithelium is one cell thick in nephron usally all cells sare homologues in a region. It is able to respond to a variety of stimulants and the late DCT and CD have 2 distinct cell types: Principal cells and Intercalated cells

Question 15

Explain about Principal and Intercalated cells

Answer 15

Principal Cells: 70% of collecting duct cells

• Reabsorb Na+ by Epithelial Na+ Channel (ENaC) on apical which is driven by 3Na-2K-ATPase on basolateral membrane
• Active Na+ ion uptake through a channel and not a cotransporter means there is no accompanying ion
• Produces a negative lumen charge which provides a driving force for Cl- ion uptake via paracellular route.
• The negative luminal charge also has an important role in K+ secretion into the lumen (ROMK present on apical membrane here not basolateral)
• Variable water uptake through Aquaporin 2 (dependent on ADH)
• Have a more distinct membrane than Intercalated cells

Intercalated Cells:

• Active reabsorption of Chloride
• Secrete H+ ions or HCO3-

Question 16

Describe how changes in pressure affect sodium secretion

Answer 16

• Changes in osmotic pressure and hydrostatic pressure in peritubular capillaries alter the proximal tubule Na+ reabsorption and hence water
• If reduced, they promote Na+ and hence water reabsorption
• If increased they inhibit Na+ and hence water reabsorption
• Proximal tubule Na+ reabsorption is stimulated by RAAS.
• Principal cells of late DCT and CD are targets for the human aldosterone
• ROMK is in thick ascending limb and latter part of DTC and CD on the apical membrane for K+ secretion

Question 17

Give a summary of fluid and electrolyte balance in the nephron

Answer 17

Question 18

What are the four neurohormonal factors involved in regulating blood pressure medium and long term?

Answer 18

There are four neurohormonal factors controlling blood pressure in medium and long term. These factors all work in part by controlling sodium balance and thus ECF volume

• Plasma is part of the ECF compartment
• Control of ECF volume controls plasma volume
• Water follows Na+ therefore controlling total body Na+ levels controls plasma volume

1. Renin-angiotensin-aldosterone system
2. Sympathetic nervous system
3. ADH
4. ANP

Question 19

How does the Sympathetic Nervous System regulate blood pressure?

Answer 19

• See CVS module, session 4
• Vasoconstriction by α1-adreoceptors
• Increased force/ rate of heart contraction by β1-adrenoceptors
• High levels of sympathetic stimulation reduce renal blood flow => decreases GFR => decreases Na+ excretion.
• Activates Na/H exchanger in PCT
• Stimulates renin release from juxtaglomerular cells leading to increased Angiotensin II and Aldosterone levels => increased Na+ reabsorption

Question 20

What is the role of ADH?

Answer 20

• Main role is formation of concentrated urine by retaining water and control plasma osmolarity
• ADH release is stimulated by increases in plasma osmolarity or severe hypovolaemia. Also stimulates Na+ reabsorption by acting on thick ascending limb and stimulating apical NaKCC co-transporter.

Question 21

What is ANP and what does it do?

Answer 21

The first 3 systems act to preserve blood volume and therefore preserve blood pressure but ANP causes loss of Na+ => reduced blood volume => reduced BP
At least 3 natriuretic hormones have been identified which act to enhance urinary excretion of sodium ions:

Atrial natriuretic peptide (ANP) is secreted by cardiac muscle when NaCl intake is increased and the volume of ECF expands. ANP causes natriuresis but its mechanism of action is uncertain.

• Synthesised and stored in atrial myocytes
• Promotes Na+ excretion in urine via vasodilation of afferent arterioles => increased blood flow increased GFR
• A high BP => stretch in Atrial cells => increased release of ANP => increased Na+ excretion, volume decreases, BP decreases
• A low BP => Atrial cells less stretch => reduce release of ANP => reduced Na+ excretion, volume increases, BP increases.
• Inhibits Na+ reabsorption along the nephron

Natriuetic hormones have also been isolated from the brain (BNP).

[*] Other effects of ANP include:

• Reducing blood pressure
• Decreasing the responsiveness of adrenal glomerulosa cells to stimuli that result in aldosterone production and secretion
• Inhibit secretion of ADH
• Decreasing vascular smooth muscle cell responses to vasoconstrictive agents.
• The latter actions of ANP are counter to the effects of angiotensin II. ANP also LOWERS renin secretion by the kidneys => lowering circulating angiotensin II level

Question 22

Explain about the baroreceptor reflex

Answer 22

Systemic BP = Co x TPR.
Mean arterial BP = CO x TPR
(Pressure = flow x resistance)

[*] The baroreceptor reflex has an important role in the short term, moment-to-moment regulation of BP by controlling peripheral resistance, heart rate and contractility of the heart. Baroreceptor firing accommodates and thus the setting of the baroreceptors increases in response to prolonged elevation in BP so the baroreceptor reflex works well to control acute changes in BP and produces a rapid response but does not control sustained increases as the threshold for baroreceptor firing resets.

• Adjusts sympathetic and parasympathetic inputs to the heart to alter cardiac output
• Adjust sympathetic input to peripheral resistance vessels to alter TPR

Nerve endings in the carotid sinus and aortic arch are sensitive to stretch; increased arterial pressure stretches these receptors which results in bradycardia and vasodilation to counteract increased mean arterial pressure

Question 23

What 3 factors influence renin release?

Answer 23

[*] The kidney contributes to the control of the peripheral resistance through the secretion of renin from granular cells of the afferent arteriole in the juxtaglomerular apparatus (JGA). The renin-angiotensin system is a biochemical cascade responsible for the regulation of blood pressure.

[*] 3 factors influence renin release:

• Baroreceptors in afferent arterioles are a key mechanism for regulating renin secretion. A drop in perfusion pressure results in the release of renin from the juxtaglomerular cells of the kidneys
• Renin secretion is also regulated by the rate of Na+ ion and Cl- ion transport across the macula densa; the higher the rate of transport of these ions to the distal tubule, the lower the rate of renin secretion.

Decreased NaCl concentration at the Macula Densa cells (due to low perfusion and therefore low GFR) causes Sympathetic stimulation to the JGA. This also increases the release of renin. Also causes Macula Densa cells to release prostaglandins => afferent arteriole vasodilation.

• Sympathetic stimulation to JGA increases release of renin (JGA = macula dena +granula cells + surrounding mesangial cells)

Question 24

What does Renin do and what does Angiotensin II do?

Answer 24

[*] Renin, a proteolytic enzyme, cleaves the protein angiotensinogen to form angiotensin I. Angiotensin I is further cleaved by angiotensin-converting enzyme (ACE) to form the active hormone, angiotensin II.

[*] Angiotensin II is a potent vasoconstrictor primarily on the vascular smooth muscle of afferent and efferent arterioles and leads to a rise in both systolic and diastolic pressure (increases TPR and thus BP). Additionally angiotensin II acts on the adrenal cortex to stimulate the synthesis and secretion of aldosterone.

[*] Other physiological responses to angiotensin II includes stimulation of thirst and secretion of ADH via action on the brain and central and peripheral stimulation of the sympathetic nervous system, thus potentiating the release of noradrenaline – angiotensin II enhances sympathetic nervous activity.

• Angiotensin II stimulates Na+ reabsorption in the kidney by stimulating Na+H exchanger in the apical membrane of PCT
• Angiotensin II stimulates ADH release at hypothalamus (stimulating thirst)
• Angiotensin Concerting Enzyme, aka kininase II, breaks down bradykinin (vasodilator)
• Angiotensin II acts largely via G-protein-coupled AT1 receptors. There are also AT2 receptors which are G-protein-coupled

Question 25

Explain the action of aldosterone

Answer 25

• Aldosterone promotes Na+ ion reabsorption from the distal nephron therefore water reabsorption; thus increasing ECF volume.
• Aldosterone activates ENaC and apical K+ channels on principal cells of collecting ducts
• Aldosterone also increases basolateral Na+ extrusion via 3Na-2K-ATPase

Question 26

How can RAAS be inhibited?

Answer 26

[*] The renin-angiotensin system can be inhibited at various points along the biochemical cascade. Several drugs have been developed for clinical use, including ACE inhibitors which prevent the generation of angiotensin II and angiotensin (AT1) receptor antagonists, which can block the action of angiotensin II.

• ACE inhibitors also promote vasodilation by preventing the breakdown of bradykinin but side effect can be a dry cough due to the accumulation of bradykinin in the lungs.

[*] The action of aldosterone can be inhibited directly by the aldosterone antagonist spironolactone that has a diuretic effect.

[*] These drugs are used for the treatment of hypertension and heart failure.

Question 27

Compare the baroreceptor reflex to the Bainbridge reflex and how does the kidney respond to increases or decreases in ECF?

Answer 27

[*] Increases in ECF volume are detected by a number of different sensors, a number of which are located in the vascular system. They are known as volume or baroreceptors.

[*] Low-pressure baroreceptors in the atria and pulmonary vasculature send signals to the brainstem via the vagus nerve. This activity modulates sympathetic nerve outflow, secretion of a hormone called ADH and reduction of ANP release. So a decrease in filling of the pulmonary vasculature and cardiac atria increases sympathetic nerve activity and causes ADH secretion, and thus water uptake.

Because of the location of these low-pressure sensors in the venous (high compliance) side of the circulatory system where the majority of the blood is, they respond to total venous volume
Distension of these low-pressure baroreceptors decreases sympathetic nerve activity.
In general a 5-10% change in pressure is needed to evoke a response.

[*] The Bainbridge reflex (where increases in right atrial pressure increase the heart rate) is more important than the baroreceptor reflex when the blood volume is raised, but the baroreceptor reflex is more important when blood volume is diminished.

[*] High-pressure baroreceptors in the arterial side of the circulatory system (carotid sinus and aortic arch) respond to pressure and send impulses via afferent fibres of the vagus nerve and glossopharyngeal nerves. Here, a decrease in blood pressure increases sympathetic nerve activity and secretion of ADH and vice versa. A change of 5-10% is sufficient to stimulate these sensors.

[*] The kidneys respond to an increase in volume of the ECF by increasing the excretion of NaCl and water and a decrease in ECF volume by decreasing the excretion of NaCl and water.

Question 28

What are the actions of ADH in TAL and CD?

Answer 28

Addition of aquaporin to Collecting Duct

• Reabsorption of water
• Forms concentrated urine
• Release of ADH is stimulated by increases in plasma osmolarity (electrolyte-water balance) or severe hypovolemia

Thick Ascending Limb

• Stimulates apical Na/K/Cl co-transporter
• Less Na+ moves out into the medulla, reduced osmotic gradient for water to exit the lumen into the peritubular capillaries from the thin ascending limb.

Question 29

Explain about Dopamine

Answer 29

• Dopaminergic neurones in kidney
• Local dopamine production (PCT cells)
• Dopamine receptors on renal blood vessels and PCT
• Have a vasodilation effect – increase renal blood flow and reduce reabsorption of NaCl

Question 30

Explain about Prostaglandins

Answer 30

[*] Prostaglandins are produced in many parts of the body and are part of a larger family of closely related vasoactive unsaturated fatty acids called eicosanoids. The kidney is one of the most active prostaglandin-producing tissues, producing prostaglandin E2 (PGE2) and prostacyclin (PG12).

• Prostaglandins have a vasodilator effect and thus increase glomerular blood flow and filtration (increase GFR) and reduce Na+ reabsorption in the presence of vasoconstrictors
• They therefore may have an important protective function by acting as a buffer to excessive vasoconstriction by the sympathetic nervous system and RAAS, helping to maintain renal blood flow.
• Important when angiotensin II levels are high

Question 31

What are NSAIDs?

Answer 31

• [*] Non-steroidal anti-inflammatory drugs (NSAIDs) inhibits prostaglandin production which in patients with diseased kidneys, may cause dramatic and severe decline in GFR (acute renal failure) which can be life threatening.
• • They inhibit the cyclo-oxygenase (COX) pathway that is involved in the formation of prostaglandins
• In these patients prostaglandins are essential to maintain normal renal function by opposing the action of vasoconstrictors (angiotensin II, vasopressin and noradrenaline from sympathetic nerve activation).
• In heart failure or hypertensive patients, NSAIDs can exacerbate the condition by causing NaCl and water retention.

Question 32

Explain about Essential Hypertension and Secondary Hypertension

Answer 32

[*] Hypertension is a sustained increase in blood pressure.

Essential hypertension (i.e. hypertension where the primary cause is unknown) accounts for 95% of all cases. Genetic and environmental factors may both be involved and the pathogenesis is unclear.

• High BP tends to run in families
• Environmental factors e.g. smoking, exercise, lcohol
• Pathogenesis unclear – recent research shows that there could dysfunctional dopamine receptors involved

In 5% of cases, a primary cause for the hypertension can be established (i.e. secondary hypertension). Examples of conditions which can cause hypertension are: chronic renal disease, renovascular disease, renal parenchymal disease, aldosteronism, dysfunctional dopamine receptors and pheochromocytoma . With secondary hypertension, it is important to treat the primary cause.

Question 33

What is Renal Vascular Disease and Renal Parenchymal Disease?

Answer 33

Renovascular disease is caused by an occlusion of the renal artery, causing a fall in perfusion pressure in that kidney.

• Decreased perfusion leads to that kidney releasing renin and activating RAAS. Vasoconstriction and Na+ retention will then take place at the other kidney which would lead to increased blood volume and increased BP.

Renal parenchymal disease:

• Early stage may be a loss of vasodilator substances e.g. prostaglandins and dopamine
• In later stage Na+ and water retention due to inadequate glomerular filtration (volume-dependent hypertension)

Question 34

What are possible adrenal causes of hypertension?

Answer 34

• Conn’s Syndrome: aldosterone secreting adenoma (enhances Na+ reabsorption leading to increased blood volume and also activates ROMK promoting loss of K+ into the urine) leading to hypertension and hypokalaemia
• Cushing’s Syndrome: excess cortisol which acts on aldosterone (mineralocorticoid) receptors causing Na+ reabsorption and water retention
• Pheochromocytoma: tumour in the adrenal medulla leading to secretion of noradrenaline and adrenaline

Question 35

Why is Hypertension known as the silent killer?

Answer 35

Hypertension the silent killer: although it may be asymptomatic, it can have unseen damaging effects on

• Heart and vasculature
• Potentially leading to heart failure, MI, stroke, renal failure and retinopathy

Question 36

How would you treat hypertension?

Answer 36

Treatment of Hypertension

• ACE inhibitors either prevent the production of Angiotensin II from Angiotensin I or are Angiotensin II receptor antagonists
• Thiazide Diuretics: inhibit Na/Cl co-transporter on apical membrane of DCT but may cause hypokalaemia (more K+ lost in urine)
• Other diuretics e.g. aldosterone antagonists (spironolactone) will also lower BP but not first line choice
• Vasodilators: Ca2+ channel blockers, reduce Ca2+ entry into smooth muscle => relaxation of vascular smooth muscle or α1-receptor blockers (reduce sympathetic tone – relaxation of vascular smooth muscle))
• Beta blockers block β1-receptors in the heart and reduces heart rate and contractility – reduces effects of sympathetic output. However Beta blocks are not used in first line treatment – would be used only if there are other indications such as previous MI

Non-pharmacological approaches to the treatment of hypertension include diet, exercise, reduced Na+ intake, reduced alcohol intake

• Lifestyle changes can have limited effect
• BUT failure to implement lifestyle changes could limit the effectiveness of antihypertensive therapy

Question 37

High BP doesn’t increase peripheral oedema but high venous pressure as seen in heart failure causes peripheral oedema. Why?

Answer 37

• In heart failure, there is reduced cardiac output and the ventricle (left in systolic dysfunction) is inadequately emptied so ventricular end-diastolic pressure and volumes increase. This is transmitted to the atrium – in the left side of the heart the increased pressure is transmitted to the pulmonary vasculature. The circulation’s increased hydrostatic forces causes water to move out into the intersticium of the lung (lung parenchyma), causing lung pulmonary oedema. On the right side of the heart, the increased pressure is transmitted to the systemic venous circulation and systemic capillary beds. The increased hydrostatic pressure forces movement of water into the tissues of organs and extremities, resulting in peripheral oedema.
• In Diastolic dysfunction, the ventricle fills inadequate and results in an inadequate stroke volume. The failure of ventricular relazation also results in elevated end-diastolic pressures.

Question 38

Why are ACE-inhibitors used to treat heart failure?

Answer 38

ACE-inhibitors have a vasodilatory effect which helps decrease the amount of work the heart has to do as they decrease the amount of fluid pumped around the body and also block some of the harmful substances in the blood such as angiotensin II that are produced as a result of heart failure. When the blood vessels are relaxed, this reduces the amount of force needed to eject blood from the heart.