Differentiate hypovolemia and dehydration
Hypovolemia = decreased effective circulating volume. Volume depletion - loss of salt and water - (intravascular space is low). May be hypo/iso/hypernatremia. Dehydration = isolated loss of water; implies hypernatremia or hypertonicity
Principle Determinants of GFR (in simple terms (2) and in detailed terms (4)):
In simple terms: Pgc (glomerular capillary pressure) & Qa (glomerular plasma flow rate.
In more detailed terms:
1. Transcapillary hydraulic pressure difference
2. Transcapillary colloid oncotic pressure difference
3. Glomerular capillary filtration coefficient
4. Glomerular plasma flow rate
Starling Forces at play in movement o fluid across glomerular capillaries
Balance between mean transcapillary hydraulic pressure (favouring filtration) and mean transcapillary oncotic pressure (which opposes filtration)
it's really the same as hydrostatic pressure - the pressure pushing water out of the capillary
Glomerular capillary filtration coefficient
Kf; Changes in Kf probably do not provide a primary mechanism for day to day regulation of GFR; Can be lowered by disease states such as kidney stones.
What would happen to GFR if there was an increased hydrostatic pressure in bowman's capsule?
GFR would decrease because the pressure of bowman's capsule would oppose the pro-filtration pressure int he glomerular capillaries.
what would happen to GFR if the glomerular capillary colloid oncotic pressure increased?
GFR would decrease because the oncotic pressure in glom capillaries opposes filtration.
Effect of afferent arteriole tone (RA) on GFR.
Increased tone would decrease renal blood flow, therefore decreasing GFR.
Effect of efferent arteriole tone on GFR
○ Biphasic effect on GFR: With moderate efferent arteriole constriction, GFR increases, but with severe constriction, GFR decreases due to an increase in the capillary oncotic pressure
Renal Autoregulation (3)
Refers to the kidney's ability to immediately respond to hemodynamic changes in order to keep mean arterial pressure in the the kidney, and therefore the GFR, constant.
Includes a (1) myogenic mechanism and (2) tubuloglomerular feedback.
Myogenic mechanism of renal autoregulation
- primarily in afferent arteriole arterial smooth muscle contracts/relaxes in response to increased/decreased vascular wall tension
- RAPID (seconds) goal: to prevent excessive renal blood flow and GFR at high pressure
when is tubuloglomerular feedback more and less effective?
- Less sensitive during volume expansion, which allows a greater delivery of fluid and electrolytes to the distal nephron to allow for correction of volume expansion
- More sensitive during extracellular volume contraction, which helps conserve fluid and electrolytes
where does renin come from?
juxtaglomerular cells of afferent arteriole in the nephron
source of angiotensinogen (2)
synthesized by proximal convoluted tubules and in the liver (main source)
Sympathetic Nervous System (SNS) Effects on GFR
The renal sympathetic nerves seem to be the most important in reducing GFR during severe, acute disturbances (i.e., hemorrhage); Rich innervation of kidney blood supply.
- Mild activation of SNS causes decreased Na and water excretion
- Mild to moderate activation of SNS has little effect on renal blood flow and GFR
- Strong activation of SNS can constrict the renal arterioles and decrease renal blood flow and GFR
Effect of NE and Epinephrine on GFR
Effect of prostaglandins on GFR
Effect of NO on GFR
What may happen to GFR in Diabetes?
- With sustained hyperglycemia, SGLT2 (glucose transporter in the proximal tubule) expression increases to absorb more glucose
- Early Diabetic Neuropathy - increased proximal tubule glucose absorption leads to hyperfiltration ( increased GFR)
generally describes an increase in urine output
an increase in urinary excretion of sodium, with or without an increase in urine volume
Effective circulating volume vs extracellular fluid volume
for most healthy people with no kidney, heart or liver disease, effective circulating volume is a fixed fraction of total extracellular fluid volume, so the 2 meanings can be used interchangeably
Modalities for sensing ECFV (3)
1. low pressure sensors in atria, ventricles, and pulmonary circulation
2. high pressure sensors in arteries (carotid, aortic arch, renal arteries)
3. others in CNS and hepatic circulation
what do high levels of BNP in blood indicate? Clinical relevance?
Higher levels can be indicative of congestive heart failure as they indicate increased volume loading on the ventricle.
Use of this test may help differentiate shortness of breath due to CHF from shortness of breath due to lung disease.
where are the low pressure sensors
areas of lower BP; Cardiac atria, R ventricle, pulmonary circulation; Places where changes in blood volume do not cause large changes in BP
where are the high pressure sensors?
stretch receptors in carotid artery, aortic arch, an arterioles of the kidney; Places that are more sensitive to pressure than volume;
how does sympathetic NS output respond to decreased ECFV (5)
Sympathetic output increases;
- - increased HR, CO
- - Increased vascular tone
- - decreased GFR
- - increased renin secretion
- - increased renal Na+ reabsorption
overall: Decrease renal Na+ excretion
how much NaCl is filtered into the filtrate
NaCl solution is freely filtered across the glom basement membrane, so Na concentration as the start of the proximal tubule is that same as Na concentration in serum.
Site of action of loop diuretics and how they work (3)
the NKCC2 transporter in the LoH. This transporter is on the apical membrane and reabsorbs 1 Na, 1 K, and 2 Cl.
Inhibition of NaCl and K reabsorption at this point can cause natriuresis (and K+ aliuresis).
By poisoning the medullary concentration gradient, loop diuretics also impair urine concentrating, therefore causing further diuresis.
Thiazides - where they work and how they work
- Inhibit the NCC NaCl transporter in the early distal convuluted tubule
- Not as potent as loop diuretics but commonly used to treat HTN
Can be combined w loop diuretics to block 2 sites simultaneously when chronic use of loop diuretics leads to upregulation of DCT Na reabsorption.