March 12 - Renal Physiology Flashcards
What are the six functions of the kidneys?
Regulation of water and electrolyte balance (input = output)
Excretion of metabolic waste products and foreign chemicals - including drugs (hydrophilic)
Regulation of blood pressure (RAAS; water and electrolyte balance)
Secretion of erythropoietin (control of erythrocyte production)
Secretion of 1,25-dihydroxyvitamine D3 (control of phosphate and calcium)
Regulation of extracellular pH
What is a major pharmacological action of the liver?
Metabolism of substances by adding a charge, which makes them more water soluble and it doesn’t cross membranes as easily, thus it can be excreted by the urine
Describe the kidneys
There are normally two, found retroperitoneal. They are approximately 150 g and the size of a fist. Each kidney is made up of 1 million filtering units called nephrons. Each nephron contains a selective filtering unit (glomerulus) connected to a series of specialized tubules. A large volume of blood is filtered each day (approximately 99%). They kidneys must reabsorb what is valuable and excrete waste.
What is urethritis?
Inflammation of the urethra
What is cystitis?
Inflammation of the bladder
What is pyelonephritis?
Infection of the kidney
How much fluid is filtered through the kidneys? How much is reabsorbed?
The normal glomerulus filtration rate is 100-125 ml/min, so about 180 L of plasma is filtered/day. 178 litres is reabsorbed a day (about 99% of what is filtred; about 99% of sodium is reabsorbed)
What is the glomerulus?
A highly specialized membrane for selective filtration. There is a network of capillaries between an afferent and efferent arteriole. There is a larger surface area for selective filtration of blood; this allows for fluid and small molecules across (but not proteins - the filtrate is essentially protein free plasma). The total movement of fluid across this membrane for all nephrons is called the glomerulus filtration rate (GFR)
In the glomerulus, there are two capillary beds in series. Explain
The afferent arteriole flows into the glomerular capillaries (filtration site). Here, plasma is filtered into Bowman’s capsule. From there, the blood flows into the efferent arteriole and then into the peritubular capillaries and vasa recta. Here plasma is reabsorbed and some plasma is secreted back into the kidneys, where is will be excreted. From the peritubular capillaries, the blood flows into venules
What are the three layers of the glomerular membrane?
The endothelial cells (perforated, pores, fenestrations, little slits) Basement membrane (Aka basal lamina; acellular (collagen, glycoprotein)) Podocytes (epithelial cells, encircle glomerular tuft, narrow slits between podocytes)
What are the different glomerular cell types?
Mesangial cells (muscle cells between the capillary loops that are able to contract to lower the GFR) Macula densa (cells located in the early distal tubule and between the afferent and efferent arterioles that detect changes in the tubular fluid) Juxtaglomerular apparatus (JGA)
Describe JGA
They contain granule cells, which secrete renin and other vasoactive chemicals (dilators and constrictors)
The macula densa detects changes in the tubular fluid, and JGA releases agents to regulate the GFR accordingly (by altering afferent and efferent arteriole tone)
What drives filtration?
Starling forces; pressure in the glomerular capillary (P sub GC), oncotic pressure of the filtrate in Bowman’s capsule (pi sub BC; approx 0 mmHg), pressure in Bowman’s capsule (P sub BC) and oncotic pressure of plasma in glomerular capillary (pi sub GC)
What forces drive filtration?
Glomerular capillary hydrostatic pressure (P sub GC)
Oncotic pressure of fluid in Bowman’s capsule (pi sub BC)
What forces oppose filtration?
Hydraulic pressure in Bowman’s capsule (P sub BC)
Oncotic pressure in glomerular capillary plasma (pi sub GC)
What is the main determinant of GFR?
The main determinant of GFR is the P sub GC (regulated very tightly). Increase in P sub GC increases GFR; decreases in P sub GC decreases GFR. Small increases of P sub GC will damage the glomerular membrane. P sub GC is tightly controlled by the afferent and the efferent arterioles. Pressure here is about 50 mmHg
What causes constriction of the afferent/efferent arteriole?
Norepinephrine and angiotensin II
What is the result of constriction of the afferent arteriole?
A drop in P sub GC
What is the result of constriction of the efferent arteriole?
A rise in P sub GC
RBF and GFR are constant over a wide range of pressure. What are the two intrarenal mechanisms that ensure this?
Myogenic
-increased BP stretches afferent arterioles - muscle constricts
-prevents an increase in P sub GC and GFR
Tubuloglomerular feedback
-tubules “talk” to glomerulus
-macula detects changes in fluid flow/content in distal tubule
-JGA releases constrictor or dilator accordingly to correct
Describe the autoregulation of RBF and GFR
An increase in blood pressure causes two things. First an increase in RBF and GFR, which increases the flow to the macula densa, which causes the release of constrictor from JGA. Second an increase of afferent arteriole, which leads to a myogenic response (constriction). All this increases the afferent arteriolar resistance
What happens if the blood pressure decreases/volume is depleted?
Intense vasoconstriction of the afferent and efferent arteriole may decrease GFR. In volume depletion and/or low blood pressure a number of vasoconstrictor substances are released; the baroreceptor reflex increases norephinephrine, decreased renal perfusion increases angiotensin II and decreased blood pressure increases vasopressin. Collectively these may cause severe constriction in the periphery and in organs including the kidney. The kidney is protected by the release of vasodilatory prostaglandins (PGE3, PGI2)
How can aspirin cause renal failure?
With volume depletion or decreased blood pressure, there is intense constriction due to angiotensin II and norepinephrine. In the periphery this is not a problem, however in the kidney, the decrease may cause filtration to stop. Prostaglandins cause vasodilation in the afferent and afferent arterioles. NSAIDS (like aspirin) block prostaglandin production, which can lead to intense constriction
What is creatinine clearance?
It is a clinical estimate. Creatinine is a natural product of the muscle metabolism and constant from day to day. Almost all urinary creatinine comes from filtration. Creatinine can be measured using 24 hours worth of urine collection and a blood sample. Creatinine clearance more or less equals GFR
What are three values of importance (in kidney function)?
Creatinine clearance (CrCl)
MDRD eGFR equation (used to estimate GFR)
Blood urea/creatinine ratio (volume depletion)
What is MDRD eGFR?
MDRD - modification of diet in renal disease
It requires consistant creatinine assay and software
It is only useful if the GFR is stable and below 60 ml/min
Why is blood urea/creatinine ratio important?
Urea is a product of protein metabolism. Urea and creatinine are freely filtered. 50% of urea filtered is reabsorbed (varied depending on volume status - it follows sodium and water reabsorption). In hypovolemia, there is enhanced sodium and water reabsorption, which increases urea reabsorption. Creatinine is not reabsorbed along the nephron. In euvolemia, blood urea/creatinine should be 0.07
Why is CrCl not the most reliable?
It varies between sexes. Also, serum creatinine must be interpreted cautiously at lower levels. A small increase may represent variation or an actual decrease in GFR (1.3 might be normal for one individual, but scary high for a different individual)
