0811 - Regulation of Body Water, Na, K Flashcards
Recognise why osmo- is different to volume-control
Osmo-control achieved through regulating H2O excretion/retention (resorption) (ADH, urine concentration and dilution) and thirst. As H2O is excreted at different rates, it will naturally change the osmolality of the ECF. Volume-control achieved through regulating NaCl excretion/retention (resorption) - Renin-Angiotensin-Aldosterone (RAA) is main effector. By changing NaCl excretion/retention (aldosterone changes reabsorption), the new osmolality of the ECF will set the volume - water will passively follow until the osmotic difference has been met. While both systems are separate, they are not independent, and both are required to control plasma volume (ADH secretion is indirectly modulated via ATII)
Explain how ADH controls osmolality
Short term - Inserts aquaporins from intracellular vesicles into apical membrane of cells in distal tubule/collecting duct. Also increases urea diffusion via urea transporters. Increasing water resorption lowers ECF osmolality. Very potent vasoconstrictor. Long-term also affects gene expression (produce more aquaporins).
Identify factors that control and modulate ADH secretion
Small (~1%) increase in effective osmolarity (i.e. not urea/glucose) causes increased ADH secretion from the pituitary. Set point 285-295mOsm. Decreases in blood pressure or blood volume also stimulate ADH. ADH is rapidly broken down (minutes). It serves to vasoconstrict the systemic vessels and antidiuretic action in DT/CD. Alcohol (blocks it) and lithium and nephrogenic issues can block ADH effects.
Outline the role of thirst in fluid homeostasis
Thirst responds to changes in osmolality (or Angiotensin II) - 2-3% increase in osmolality induces strong desire to drink. Much less sensitive to blood loss/decrease in BP (10-15% change required). Works with ADH to regulate osmolality - desire to drink and conservation of H2O. Satiation faster than plasma response - receptors are in oropharynx and upper GI tract, so thirst returns until osmolality corrected.
Recognise ‘effective circulating volume’ and how the body measures it
CVe is the portion of ECF within the vascular system and ‘effectively’ perfusing tissues. It is closely tied to Na+ balance, and the kidneys alter NaCl excretion due to changes in CVe. When effective perfusion (CVe) drops, Na+ is retained, increasing ECF volume. Measured by sensors - predominantly vascular baroreceptors: Low pressure (capacitive - volume sensed by compliance): Cardiac atria; neural and hormonal (ANP) Pulmonary vascular (neural) High pressure (respond to BP and associated deformation): Carotid sinus (neural) Aortic arch (neural) Juxtaglomerular apparatus: afferent arterioles (hormonal via Renin). Also hepatic and CNS sensors, but not well understood. Effectors - Kidney (RAA), Vasculature (filtration increasing ISF), CNS (thirst)
Where are the sensors for RAA?
Sensors measure CVe - vascular sensors are most important, but also hepatic and nervous sensors that are not well understood. Vascular sensors are: Low pressure (capacitive - volume sense via compliance) - cardiac atria (neural and ANP), pulmonary vasculature (neural) High pressure (respond to BP and deformation) - carotid sinus (neural), aortic arch (neural), juxtaglomerular apparatus (hormonal via renin).
Where do the RAA sensors target?
Targets for the sensors - kidney, vasculature (filter more or less out of the capillaries), and CNS to create either more or less thirst. Kidney is most important, and can have a systemic or local response - systemic will override local: Systemic (over whole kidney) - slow response (hours to days) with different elements and targets involved. Local (single nephron) through autoregulation of GFR. Tubulo-glomerular feedback (fast response s-min), and autoregulation of single nephron perfusion via ATII (slow 30-60min) - decreasing GFR and RBF via afferent arteriole constriction
Outline Renin/JG cells and the systemic response to volume control
Renin contained in granules in juxtaglomerular cells (specialised endothelium where afferent arteriole meets glomerulus). JG cells are capable of sensing the high-range of blood pressure (mechanoreceptors) and can release renin in response to changes. Systemic response - mediators are nerves, and hormones including RAA (and ANP et al). Controls BP by altering NaCl reabsorption rates along the tubule.
Discuss RAA as a system
Renin is released by juxtaglomerular apparatus in response to BP changes (adrenoreceptors affect the release threshold, and ATII and aldosterone secretion provide negative feedback). Renin is a peptidase, converting angiotensinogen (always in blood, from liver) to AT-I. ACE in endothelial cells (particularly the lungs and kidneys) then converts AT-I to AT-II. AT-II is a vasoconstrictor (thus increasing BP and lowering RBF and GFR), increases craving for salt and thirst, and stimulates Na+ reabsorption in PT. When AT-II hits adrenal gland, it promotes aldosterone synthesis/release, which also leads to more Na+ reabsorption and leads to nor/adrenaline release.
Outline normal tubular reabsorption.
Normally, there is constant Na+ delivery to CD due to: Autoregulation of GFR Glomerulo-tubular balance (colloid osmotic pressure) - increased GFR leads to increased colloidosmotic pressure in capillary leads to increased NaCl reabsorption in proximal tubule (small effect). Load-dependency of Na+ reabsorption in TAL and DT/CD. Increased Na+ load = increased NaCl reabsorption (they don’t know how).
What happens to tubular reabsorption in hypervolaemic state?
In Hypervolaemic state, the afferent vessel is dilated, increasing GFR. Then, along the tubule - important to remember that reabsorption goes UP in TAL/DT: PT - NaCl reabsorption lowered. Lower SY activity, and lower AT-II. Most important. TAL/DT - Much more NaCl is hitting the area, so by load-dependency, more is reabsorbed. CD - Reabsorption drops because of less ADH and aldosterone.
What happens to tubular reabsorption in hypovolaemic state?
In hypovolaemic state, afferent vessel is constricted (high AT-II, SY), lowering GFR. Then vice-versa along the tubule, noting TAL/DT is again counter-intuitive. PT - NaCl reabsorption increased due to SY activity, AT-II. Most important. TAL/DT - NaCl reabsorption lowered due to load-dependency. CD - H2O/NaCl reabsorption increased due to ADH and aldosterone.
Discuss the hierarchy in homeostatic osmo and volume control. KEY EXAM CONCEPT
KEY EXAM CONCEPT - Knows textbooks say it differently - he doesn’t care what we write as long as it makes sense. Where osmocontrol (ADH and thirst) and volume control (RAA etc) compete, osmocontrol prevails as it is much stronger and much faster in its response. E.g. when heavy sweating (so electrolyte loss), thirst is satiated via drinking H2O, rather than by salt intake. Therefore, for the cardiovascular system, decreased Na (volume issue remember) seems to be less of a problem to deal with than hypovolaemia (which is kind of an osmo-thing).
