Cardiovascular Regulation (B Smaill & R Ramchandra) Flashcards
How much fluid is in ICF vs ECF?
- Intracellular cellular fluid (ICF) is 2/3 TBW, and extracellular fluid (ECF) is 1/3 TBW.
- ECF compartment subdivides into interstitial fluid (ISF) and plasma
Name the ody fluid competments
- Intracellular cellular fluid (ICF) is 2/3 TBW, and extracellular fluid (ECF) is 1/3 TBW.
- ECF compartment subdivides into interstitial fluid (ISF) and plasma.
Describe the movement between ICF and ISF
Water movement between cells (ICF) and interstitial space (ISF) is driven by osmotic gradients across cell membrane.
Therefore, water will be distributed so that osmolality in intracellular and interstitial fluids is equalised.
Describe the Osmoreceptors
Osmoreceptors
- Supraoptic and paraventricular nuclei of hypothalamus sense changes in effective plasma osmolality by altering their volume.
- This modulates sensory output from these cells that control synthesis and release of antidiuretic hormone (ADH/vasopressin) by posterior pituitary gland.
There is a tight linear relationship between ADH and plasma osmolality over range of 280-295 mOsm/L.
- When [ADH] is increased, there is a graded incerase in water permeability of collecting ducts of kidney.
- Aquaporins (preformed water channels) are released from vesicles, inserted into apical membrane of collecting ducts.
- This increases water reabsorption and leads to excretion of concentrated urine by the kidney. Opposite occurs when [ADH] is reduced, with release of diluted urine.
- Finally, activation of osmoreceptors by increased plasma osmolality also stimulates thirst centres in hypothalamus.
Describe the movement between ISF and Plasma
(between ECF)
Water movement between interstitial space (ISF) and vascular compartment (plasma) is determined by net gradient in hydrostatic and osmotic gradients at the level of the capillaries. A simple representation of this balance is given in Starling equation:
Describe the Electrolyte/ions movement
Electrolytes move freely in ECF across capillary membrane between ISF and plasma (although plasma proteins do not).
However, electrolytes movement between ECF and ICF is controlled by pumps and transporters in the cell membranes.
If isotonic saline is added to ECF (e.g. by infusion), what happens?
What happens if hypotonic saline is added?
If isotonic saline is added to ECF (e.g. by infusion), ECF volume increases, while ICF volume is unchanged.
- There will be no fluid movement because there is no difference in osmotic pressure between compartments
- Na+ added will remain in ECF due to activity of Na+/K+-ATPase.
On the other hand, addition of hypotonic saline to ECF, ECF and ICF volume both increases.
- It will reduce ECF osmolality causing water to move into the ICF.
- At equilibrium, osmolality of both ICF and ECF compartments will be reduced, and both volumes will be increased.
Briefly how does changes in ECF affect the CV performance
Changes in ECF volume also affects the plasma volume, and therefore impact on cardiovascular performance
Describe what would happen when cardiac filling decreased
(Cardiothoracic receptors) (5)
Cardiac receptors relay sensory information to hindbrain, which reflects state of cardiac filling (influenced by blood volume and extracellular volume). Both myelinated and unmyelinated cardiac receptors sensitive to small changes in cardiac filling.
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Reduced cardiac filling (due to decreased BV) triggers reduced cardiac receptors activity. leads to
- increased sympathetic outflow to heart and vessels,
- reduced cardiac vagal activity and
- increased catecholamine secretion by adrenal medulla.
- It also elicits a complex series of neuro-humoral responses that affect extracellular fluid volume (try to restore ECF).
- As a result of increased renal sympathetic activity, renin is secreted into bloodstream, which activates RAAS cascade.
- When there is increased circulating [angiotensin II], ADH release is also increased, thirst is also augmented.
- Supplementing effects of ADH, increased [aldosterone] favour sodium retention.
- Moreover, reduced cardiac receptor activity (due to reduced filling) increases ADH synthesis and release. Therefore, plasma ADH levels are controlled by both osmoreceptors and cardiac receptors.
- As a result of increased renal sympathetic activity, renin is secreted into bloodstream, which activates RAAS cascade.
- In addition, thirst is directly stimulated by reduced cardiac receptor activity and is augmented by increased circulating levels of angiotensin II. This cascade of neurohumoral responses is reversed when cardiac receptor firing is increased.
It is important to note that >10% blood volume loss (ECF) also decreased systemic arterial pressure. This can result in decreased systemic arterial baroreceptor firing, which elicits neurohumoral responses that are qualitatively similar to those outlined above.
What happens in the cardiovascular system when there is loss of blood volume?
If BV is reduced, cardiac filling decrease_s and cardiac receptor activity is reduced. If the loss is more than 10%, l_oss of BV artierial pressure falls and arterial baroreceptor firing is reduced.
When BV is reduced, there is a decrease in peripheral venous pressure, which reduces venous return to heart.
The resultant decrease in cardiac filling reduces SV.
- Reduced cardiac filling produces reflex autonomic responses that tend to maintain CO and MAP. These are due to _decreased firing of cardiac receptor_s and arterial baroreceptors (>10% blood loss).
- These reflex responses may be viewed as maintaining cardiovascular function in face of reduced BV. There are separate “lines of defense”. In absence of appropriate reflex adjustments, CO and MAP will fall.
- In the face of reduced cardiac filling, there is increase in HR and cardiac inotropic state to preserve CO.
- In the face of reduced CO, there is constriction of resistance vessels (skeletal muscle, renal, splanchnic and cutaneous circulations) to preserve MAP; or alternatively, there is diversion of blood flow from non-essential circulations to preserve coronary and cerebral oxygen supply.
- In the face of reduced BV, there is venoconstriction to preserve venous return; and together, there is increased ADH and RAAS activation to restore BV.
Describe the 3 types of acute loss of blood volume
Non-Hypotensive Haemorrhage
With blood loss of <10%, mean arterial pressure (MAP) is unchanged, although pulse pressure reduces.
This is because neural-mediated reflex mechanisms are sufficient to maintain cardiovascular homeostasis. This is called non-hypotensive haemorrhage.
- There is almost no change in systemic arterial baroreceptors firing as expected since there is no change in MAP.
- However, there is significant decreased cardiac receptors firing. This results in:
- Increased circulating [aldosterone] and [ADH]
- Increased HR and cardiac inotropic state etc. (not shown in figure)
Therefore, it has been argued that cardiac receptors play a central role in maintaining cardiovascular homeostasis for BV fluctuations of <10%.
Hypotensive Haemorrhage
With blood loss of >10%, there is a graded fall in MAP reflecting extent of BV deficit. This is called hypotensive haemorrhage.
- In addition to decreased cardiac receptors firing, there is progressive reduced arterial baroreceptor firing due to MAP decline. This is accompanied by:
- Further increases in [aldosterone] and [ADH]
- Further increases in HR and cardiac inotropic state
- Further constriction of resistance and capacitance vessels
Haemorrhagic Shock
Where blood loss is extreme and remains uncompensated for long periods, simple replacement of BV deficit may not restore cardiovascular homeostasis. This is called haemorrhagic shock.
- In addition to effects above, blood flow to certain vascular beds may be almost completely shut down.
Describe the changes after drop in blood volume (restoration of fluid loss)
Fluid Shift From Interstitial Space To Plasma
In response to blood loss, reflex constriction of precapillary vessels (increased precapillary resistance) reduces capillary hydrostatic pressure, which shifts balance between capillary hydrostatic and oncotic pressures in favour of fluid absorption.
- This gives rise to water movement/translocation from ISF to plasma/blood (vascular compartment).
- Skeletal muscle with its relatively large ISF volume provides important reservoir for this “internal transfusion”. The process is initiated rapidly and is limited by plasma protein dilution. However, up to 800mL fluid may be mobilized via this pathway.
Restoration Of Extracellular Fluid Volume
In response to blood loss, neurohumoral cascade is triggered to regulate ECF volume (flowchart above).
- Increased circulating levels of ADH, angiotensin II and aldosterone favours water and sodium retention by kidney and augments thirst drive. This alters the balance between fluid intake and fluid output so that ECF volume is restored.
- Time-courses of component effector mechanisms are somewhat different. Serum ADH is elevated minutes after a moderate loss of blood volume, but aldosterone begins to rise only after an hour or so.
Overall, these neurohumoral mechanisms operate over medium-term and ECF volume is restored in 12-72 hours.
Restoration Of Red Cells And Other Blood Constituents
After blood loss, it takes over days to weeks to restore red cell volume and synthesis of other blood constituents.
- Immediately after acute blood loss, small amounts of preformed albumin are transferred into circulation.
- However, bulk of plasma protein deficit is restored by hepatic synthesis over 3-4 days.
- Red cell synthesis is stimulated by erythropoietin over 4-8 weeks, which is generated in kidney due to low oxygen tension.
When does non-hypotensive and hypotensive haemorrhage occur?
Non-Hypotensive Haemorrhage
With blood loss of <10%, mean arterial pressure (MAP) is unchanged, although pulse pressure reduces.
Hypotensive Haemorrhage
With blood loss of >10%, there is a graded fall in MAP reflecting extent of BV deficit.
Describe the responses to altered posture
It will now be argued that cardiovascular adjustments in altered posture are identical to those in non-hypotensive haemorrhage.
- On rising from a horizontal to an upright position, gravitational effects increase hydrostatic pressure acting on blood vessels in lower extremities. As a result, superficial veins in legs and ankles deform and 400-500mL BV shift from central thoracic reservoir to lower limbs.
- This “internal haemorrhage” reduces effective BV, decreasing cardiac filling and reducing SV. Therefore, neural-mediated reflex mechanisms will maintain MAP:
- Increased HR and cardiac inotropic state will minimise fall in CO.
- Constriction of resistance vessels (particularly in skeletal muscle) increases total peripheral resistance.
Describe the Long Term Regulation Of Systemic Arterial Pressure - Baroreceptors
and a study that looks into the role of arterial baroreceptors
It is clear that systemic arterial baroreceptors play an important role in maintaining arterial pressure in short-term. Extent to which these receptors monitor and regulate arterial pressure in long-term is more controversial.
Hypertension: Resetting of Arterial Baroreceptors
In hypertension, it has been demonstrated that entire baroreceptor function curve is shifted to right so that normal levels of baroreceptor firing occur at higher arterial pressures. This shift has been defined as “resetting of the arterial baroreceptors”.
- It is consistent with observation that systemic arterial baroreceptors are slowly adapting receptors, whose output will return to control levels over a period of hours to days when exposed to a sustained change in arterial pressure.
- Baroreceptor function is actively modified by CNS via efferent nerves. On this basis, it has been argued systemic arterial baroreceptor afferents provide information on beat-to-beat changes in arterial pressure, but cannot be a reliable source of information on systemic arterial pressure.
Experiment: Role of Arterial Baroreceptors
In experimental studies, both carotid and aortic baroreceptors have been surgically denervated. Long-term monitoring of arterial pressures in denervated animals and sham-operated controls demonstrates that:
- In denervated animals, there is a much wider variation of beat-to-beat arterial pressure.
- However, in denervated animals, there is only short-period increase in average arterial pressure, then returns to control levels.
Therefore, arterial baroreceptors buffer short-term changes in arterial pressure (such as caused by altered posture) around a set point. Because sino-aortic denervation does not lead to sustained hypertension, arterial baroreceptors does not have significant influence on long-term average arterial pressure. Other mechanisms must also be involved in maintaining long-term average pressure control at set-point.
