Renal blood flow/glomerular filtration Flashcards
Components of a nephron?
- Glomerulus
- Tubule
Components of a nephron
-Glomerulus (glomerular capillaries) function?
Filters blood
Components of a nephron
-Tubule function?
Converts filtrate into urine
Components of a nephron
-Both the glomerulus and the tubule are surrounded by?
Both the glomerulus and the tubule are surrounded by the blind end of the tubular epithelium…bowman’s capsule (glomerular capsule)
The space between the capsule and the glomerulus is known as?
-What happens in this space?
-Bowman’s space-filtrate passes from blood to tubular system through this space
2 types of nephrons?
- Cortical
- Juxtamedullary
Cortical nephrons
- Short loops of Henle
- Surrounded by peritubular capillaries
Juxtamedullary nephrons
- Long loops of Henle
- Long efferent arterioles which divide into specialized peritubular capillaries called the vasa recta
- Functions to concentrate urine
Renal blood flow
-Oxygen consumption of renal tissue is higher than that of brain-Why?
Related to high rate of active Na+ reabsorption (drives Na+/K+ ATPase)
Renal blood flow
-Blood flow to cortex compared to medulla?
Cortex receives more blood
Where does the renal medulla get its blood from?
the vasa recta
RBF determined by?
RBF is determined by pressure gradient between renal artery and renal vein divided by the vascular resistance
Glomerular filtration: first step in urine formation
- Plasma is filtered under pressure from glomerular capillaries into Bowman’s capsule
- Normally, glomerular filtrate is essentially free of blood cells and proteins but otherwise identical to plasma
- Glomerular filtrate is heavily modified as it passes down the nephron
- Urine is very different from glomerular filtrate
Clinical application
- Estimation of GFR is essential in assessment of renal function
- Total GFR?
Total GFR is the sum of the filtration rate in all functioning nephrons and therefore is an index of functioning renal mass
Clinical application
- GFR estimate can be used to evaluate the severity and course of renal disease
- A decrease in GFR indicates? Most often resulting from?
Disease progression most often resulting from a decrease in net permeability due to loss of filtration surface area
-Increase in GFR indicates at least partial recovery
Glomerular membrane: a molecular sieve
- Passage of water and small solutes? Concentrations on each side of the membrane?
- Passage of large molecules (proteins) and formed elements?
- Free passage of water, small solutes (glucose, aas, electrolytes):concentrations are the same on both sides of the membrane
- Passage of large molecules (proteins) and formed elements is impeded
How much protein is filtered into Bowman’s capsule under normal conditions?
Only very small amounts of proteins are filtered into Bowman’s capsule
Structure of glomerular membrane
- Three distinct layers
- Inner layer?
- Middle layer?
- Outer layer?
- Inner layer-Fenestrated capillary endothelium
- Middle layer-Glomerular basement membrane
- Outer layer-Podocyte epithelium
Structure of glomerular membrane
- Three distinct layers
- Fenestrated capillary endothelium-highly permeable to?
Highly permeable to water and dissolved solutes
Structure of glomerular membrane
- Three distinct layers
- Glomerular basement membrane
Collagen, proteoglycans contain anionic (negative) charges
Structure of glomerular membrane
- Three distinct layers
- Podocyte epithelium-Function of the slit pores?
Slit pores between podocytes restrict large molecules
Slide 15 picture?
?
Mechanism of filtration
-Based on?
Based on size and charge of molecules
- Larger molecules more restricted than smaller
- Anionic molecules are restricted more than neutral or cationic
Graph on slide 17
?
Clinical application
- Some kidney diseases cause loss of negative charge on the basement membrane before noticeable changes in renal structure
- Called?
- Results in?
- Minimal change disease or nephropathy
- Results in filtration of proteins (especially albumin) and their appearance in urine (proteinuria)
- More extensive renal injury often results in large amount of protein in urine
Physical forces affecting glomerular filtration
-GFR is a product of 3 physical factors?
- Hydraulic conductivity (Lp) of glomerular membrane (permeability of capillary wall)
- Surface area for filtration
- Capillary ultrafiltration pressure (Puf)
What is the product of the hydraulic conductivity and the surface area for filtration?
Ultrafiltration coefficient Kf
How can the ultrafiltration pressure be used to calculate GFR?
GFR = Kf x Puf
Normal GFR
- in ml/min?
- L/day?
- 125 ml/min
- 180 L/day
Mechanisms for altering GFR
-Altered Kf?
Mesangial cell concentration
Mechanisms for altering GFR
-Altered Puf?
Changes in Pgc
Pgc (pressure in glomerular capillaries?)
-Determined by 3 factors?
- Renal arterial blood pressure
- Afferent arteriolar resistance
- Efferent arteriolar resistance
Glomerular mesangial cells can alter Kf
-Contraction of mesangial cells has what effects?
Shortens capillary loops, lowers Kf, and thus lowers GFR
Puf is determined by?
Hydrostatic and colloid osmotic pressures in glomerular capillaries
Puf difference of three pressures?
slide 24?
Glomerular filtration
-Depends on?
Depends on NET filtration pressure
Slide 25
Glomerular and peritubular capillary starling forces
slide 26?
Control of GFR by adjusting resistance of afferent and efferent arterioles
-Afferent arteriolar constriction
- Greater pressure drop upstream of glomerular capillaries
- Pgc decreases, which decreases GFR
- Renal blood flow decreases due to increased resistance
Control of GFR by adjusting resistance of afferent and efferent arterioles
-Efferent arteriolar constriction
- Pooling of blood in glomerular capillaries
- Increased Pgc increases GFR
- Renal blood flow decreases
The ‘garden hose’ analogy
Review this analogy as it makes it very easy to understand
Probably should know the graphs on slide 33 and 35
?
Renal blood flow
-Regulated by?
- Regulated by several mechanisms in order to control GFR
- Vascular resistance to RBF is primarily determined by afferent and efferent arterioles
- Controlled by sympathetic nervous system (NE) and various hormones along with internal (myogenic, T-G feedback) control mechanisms
Renal blood flow
-Autoregulation?
Process that regulates GFR over a MAP range between 80 and 170 mmHg
Effects of sympathetic stimulation
- Constriction of afferent and to a lesser extent, efferent arterioles
- Decreased RBF and GFR
- Diverts the renal fraction to vital organs
- Increased renin secretion by granular cells
Effects of sympathetic stimulation
- Increased renin secretion by granular cells
- Leads to production of? What are its effects?
- Angiotensin II is produced-restores BP (systemic vasoconstriction)
- Angiotensin II promotes arteriolar constriction (efferent > afferent), raises BP, and stabilizes GFR (moderate ang II)
- Stimulates Na reabsorption in proximal tubule, thick ascending limb of Henle’s loop, DCT, CD
Effect of renal prostaglandins?
-Release of prostaglandins enhanced by?
- Renal prostaglandins dampen vasoconstriction by ang II and symp. activity
- Release of prostaglandins enhanced by ADH
Control of GFR and RBF-Effects of hormones/autacoids
-Effect on GFR by NE, Epi, and endothelin?
Decrease GFR
-Effect on GFR by ang II?
No change (prevents decrease)
-Effect on GFR by NO and prostaglandins?
Increase GFR
Effect of changes in Starling forces on GFR and RBF
-Vasodilate afferent arteriole? Examples?
Increase RBF and GFR
Examples-prostaglandins E2/I2, bradykinin, NO, dopamine, ANP
Effect of changes in Starling forces on GFR
-Vasodilate efferent arteriole? Examples?
Decreases GFR
Examples-ACE inhibitors, ARBs
Effect of changes in Starling forces on GFR and RBF
-Constriction of afferent arteriole? What would do this?
Decrease RBF and GFR
Sympathetics
Effect of changes in Starling forces on GFR and RBF
-Constriction of efferent arteriole? What would do this?
Maintain or increase GFR
Ang II
Autoregulation
- The kidney guards filtration carefully
- This is accomplished by the glomerulus being situated between 2 arteriolar beds. Vascular tone in these 2 beds?
- Protects the delicate glomerular architecture at times of high blood pressure
- Preserves GFR at times of low systemic BP
Autoregulation of RBF and GFR
-Process whereby RBF and GFR are maintained constant regardless of marked changes in BP by adjustments of afferent and efferent arteriolar resistance
Autoregulation of RBF and GFR
-Effective range of control?
Effective range of control is between approximately 75-160 mmHg
Autoregulation of RBF and GFR
-What would happen without autoregulation?
Without autoregulation, a small increase in BP would result in large increases in fluid excretion and volume depletion
Mechanisms for autoregulating RBF and GFR
-Myogenic responses to?
Increased systemic arterial pressure
Mechanisms for autoregulating RBF and GFR
-Tubuloglomerular feedback responses to?
Increased or decreased GFR
Myogenic mechanism of autoregulation
- Resistance of blood vessels to stretch when exposed to high arterial pressure
- Via contraction of vascular smooth muscle in response to stretch with increased movement of Ca into cells
- Prevents increases in RBF and GFR when BP increases
Tubuloglomerular feedback
- Autoregulation of GFR by the rate of fluid NaCl delivery to the macula densa
- Feeds back to the kidneys to control renal afferent and efferent arteriolar resistance
Tubuloglomerular feedback
-This process is regulated by the?
Juxtaglomerular apparatus which consists of the macula densa cells in the distal tubule and the juxtaglomerular cells in the walls of the afferent and efferent arterioles
Tubuloglomerular feedback
-Process?
- The macula densa cells sense NaCl concentration in the distal tubule
- Feeds this information back to JG cells to adjust arteriolar resistance
- Ensures constant delivery of Na to distal tubule and prevents changes in renal excretion
- Renin release is also regulated here
3 components of the juxtaglomerular apparatus?
- Macula densa
- Extraglomerular mesangial cells (lacis cells)
- Juxtaglomerular (granular) cells in afferent and efferent arteriole smooth muscle
Juxtaglomerular apparatus
-macula densa
in wall at beginning of DCT
Juxtaglomerular apparatus
-how does it respond to changes in BP?
Maintains GFR nearly constant
Tubuloglomerular feedback response to increased renal perfusion pressure?
Results in constriction of afferent arteriole with a decrease in GFR
Vasoconstriction in response to tubuloglomerular feedback is mediated by?
Adenosine
Tubuloglomerular feedback response to decreased renal perfusion pressure?
Flow chart on slide 51!
Tubuloglomerular feedback response to decreased renal perfusion pressure
-Local responses which may be mediated via NO will cause?
afferent arteriolar dilation
A couple clinical applications at the end you should probably review
…
Renal functional unit= nephron
-What happens to the number of nephrons as a person ages?
The number of nephrons decreases with age
