Regulation of ECF Volume - Pt 1 Flashcards
What are the major ECF and ICF osmoles?
ECF - Na+ and Cl-
ICF - K+
What is regulation of ECF volume equal to?
Regulation of body Na+
What is the distribution of total body water?
ECF - 14l (1/3) with 3l in plasma and interstitial fluid is 11l
ICF - 28l (2/3)
Total 42l
What does changes in Na content of the ECF lead to?
Changes in ECF volume and will affect volume of blood perfusing the tissues - effecting circulating volume and BP
What is regulation of Na basically dependant on?
High and low pressure baroreceptors
Describe the renal response to decreased ECF volume (hypovolaemia)
Increase salt and H2O loss (vomiting, diarrhoea or excess sweating) - Decreases PV, venous pressure, VR, atrial P, EDV, SV, CO then BP which decreases carotid sinus baroreceptor inhibition of sympathetic discharge
What does increase sympathetic discharge lead to?
Increase vasoconstriction, total peripheral resistance and increase BP towards normal
By increased renin and renal constriction
What does decreased atrial pressure and carotid sinus baroreceptor discharge lead to?
Increase ADH release - may cause hypo-osmolarity
What does increased renin lead to?
Increased angiotensin II - increased proximal tubule NaCl and H2O reabsorption
Increased aldosterone - increased distal tubule NaCl and H2O reabsorption
What is the effect of sympathetic discharge specifically on the kidneys?
Increased renal VC nerve activity then increased renal arteriolar constriction and an increase in renin
What is the effect of increased renin specifically on the kidneys?
Increased angiotensin II - decreased peritubular capillary hydrostatic pressure (increased oncotic pressure) and increased Na reabsorption from proximal tubule so less Na excreted
What are changes in proximal tubule Na reabsorption due to?
Changes in rate of uptake by peritubular capillaries determined by oncotic pressure
greater absorptive forces in peritubular capillaries
What happens to oncotic pressure when NaCl and H2O is lost?
Oncotic pressure forces increase even more than normal so can reabsorb 75% of the filtrate in the proximal tubule
How does GFR remain largely unaffected?
Autoregulation maintains GFR and VC of afferent and efferent means little effect on GFR until volume depletion causes decrease MBP
What 2 things mainly maintain GFR?
Construction of afferent due to to sympathetic VC coupled with angiotensin II mediated constriction of efferent arterioles
What controls the regulation of distal tubule Na reabsorption?
Aldosterone - adrenal cortical steroid hormone
What is aldosterone secretion controlled by?
Reflexes involving the kidneys themselves
Juxtaglomerular cells (JG) at macular densa
What are juxtaglomerular cells?
Epithelial cells with plentiful granules which are on smooth muscle of afferent arteriole before entering the glomerulus where they become specialised
What is the macula densa?
Histologically specialised loop of distal tubule
What do JG cells produce?
Renin which acts on large protein in alpha2 globulin fraction of plasma proteins - angiotensinogen
Where is angiotensin produced?
Liver constantly produces angiotensinogen in the plasma
What contains ACE enzyme?
Blood vessel endothelium - converts ANGI to ANGII in plasma
Greatest conversion occurs as blood passes through pulmonary circuit
What does angiotensin II stimulate?
Aldosterone - secreting cells in zona glomerulosa of adrenal cortex
What is the rate limiting step of aldosterone?
Release of renin as angiotensinogen is always in the plasma
What controls the increase of renin release?
Pressure in afferent arteriole at level of JG cells decrease - renal baroreceptors so less distention, more secretion
Sympathetic nerve activity via B1 effect
Decreased NaCl at macula densa delivery increases renin
What controls the inhibition of renin release?
Angiotensin II feeds back
ADH inhibits renin release by osmolarity control
What provides the basis of tubuloglomerular balance?
Close relationship between afferent arteriole with JG cells and macula densa
What happens in hypovolaemia?
Increased proximal and distal tubule Na reabsorption together with osmotic equivalents of H2O - helps restore volume deficits mediated by CV reflexes
Why is angiotensin II important in body’s response to hypovolaemia?
Stimulates aldosterone - NaCl and H2O retention
Vasoconstriction - increases TPR
Acts on hypothalamus to stimulate ADH secretion - increase H2O reabsorption from CD
Stimulates thirst mechanism and salt appetite
What does aldosterone directly effect?
Increase Na reabsorption which increases volume and maintain osmolarity
What does GFR increase lead to?
Flow through tubule increases so flow past macular densa increases - paracrine from macular densa to afferent arteriole - afferent constricts - resistance increases - hydrostatic pressure in glomerulus decreases so GFR decreases
What contributes to GFR constancy?
Tubuloglomerular feedback
What happens if a patient has lost 3l of salt and water from ECF and drinks 2l of pure water?
Opposing inputs to ADH secreting cells
Decreased ECF osmolarity means inhibition of ADH via osmoreceptors
Decreased ECF volume means increase ADH via baroreceptors
What has primary effect is ECF osmolarity and volume is decreased?
Volume considerations
ADH will be increased as baroreceptors
What happens when volume in restored in hypovolaemia?
Osmolarity will be normalised then again be the main determinant of ADH
So if loss salt and water - replace with salt and water
