Glomerular Filtration and Regulation Flashcards
3 functions of each nephron
Glomerular filtration
Tubular reabsorption
Tubular secretion
Glomerular filtration rate (definition, normal value, used for)
Volume of plasma filtered from the glomerular capillaries per unit time
Normal: 90-120 mL/min
Used to evaluate the presence and severity of kidney injury and progression of kidney disease
How much of total body water is ICF vs ECF
ICF: 2/3
ECF: 1/3
What type of cells make up the visceral vs parietal layer of Bowman’s capsule
Visceral: podocytes (specialized epithelial cells)
Parietal: epithelial cells
What is the space between the interdigitated foot processes called?
Filtration slits
In life covered by a membrane
2 factors that influence selective filtration in the glomeruli
Charge (GBM is negatively charged)
Size (not permeable to large molecules)
Alport’s syndrome
Genetic defect in type 4 collagen of glomerular basement membrane
X-linked disease
See kidney failure, deafness, blindness
Nephrotic syndrome
Disease of podocytes/slit diaphragm
3 things that regulate glomerular filtration
Renal blood flow
Starling forces
Filtration coefficient
What 2 forces
- Push fluid out
- Pull fluid in
- Hydrostatic pressure in capillary, oncotic pressure in urinary space
- Oncotic pressure in capillary, hydrostatic pressure in urinary space
Permeability coefficient
Product of intrinsic permeability of the capillaries and surface area
Autoregulation
The intrinsic mechanism of the kidneys by which renal blood flood and thus GFR are maintained over a range of aortic pressure
3 factors that influence the hydrostatic pressure of glomerular capillaries
Systemic arterial pressure (effect is buffered by autoregulation)
Afferent arteriole resistance
Efferent arteriole resistance
What happens if both afferent and efferent arterioles constrict?
Renal blood flow is reduced
GFR depends on the relative balance of the vasoconstrictors/dilators available and their strength of action (AA more, GFR falls. If EA more, GFR will remain the same or rarely increase)
Characteristics of an ideal marker for GFR measurement
Small solute
Completely filtered
Non-secreted by renal tubules and GI tract
Excreted unchanged in the urine
Urinary appearance (clearance) is equal to GFR
Not expensive and easy to measure
Formula to calculate the renal clearance
C = U/ P x V C: renal clearance U: [ ] of substance in urine P: [ ] of substance in plasma V: urine flow rate
Inulin
Gold standard to measure GFR but expensive and cumbersome to assay
Mainly used in studies
Creatinine
Most commonly used to measure GFR
More practical and less expensive
Less accurate (significant amount of tubular secretion. Increase GI excretion at lower GFR)
Renal autoregulation works within a range of what mean arterial BPs
70-160 mmHg
3 responses in renal autoregulation
Myogenic response
Tubuloglomerular feedback
Neuro-hormonal vasoactive response
Myogenic response
Walls of afferent arterioles are made of smooth muscle cells
These blood vessels stretch when there is increased blood flow
Stretch reflex causes vasoconstriction of afferent arterioles and brings an increased GFR back to a normal range
Tubuloglomerular feedback
When GFR decreases, the kidney tries to compensate
Links Na and Cl concentration of the filtrate at the macula dense with control of renal arteriolar resistance
2 components: afferent and efferent arteriolar feedback
Help renal autoregulation and tubular reabsorption
Basically activates the RAAS system, and causes dilation of AA and constriction of EA
3 cell types in the juxtaglomerular apparatus
Juxtaglomerular cells in the walls of afferent arterioles
Macula dense (of DCT)
Extraglomerular mesangial cells (contractile)
Neural regulation of GFR
Sympathetic nerve fibers innervate both afferent and efferent arterioles
Excessive sympathetic stimulation = renal vasoconstriction (drop GFR)
Parasympathetic = renal vasodilation (via NO)
3 vasoconstrictors
Norepinephrine/epinephrine Endothelin Angiotensin 2 (preferentially efferent arterioles)
3 Vasodilators
NO
Prostaglandin (works on AA)
Bradykinin
Drugs that reduce GFR
NSAIDs (less prostaglandins, more AA constriction)
ACEIs
ARBs
SGLT2 inhibitors (more Na to macula densa)
2 responses to decreased GFR and decreased NaCl delivery to the macula densa
Vasodilation of afferent arteriole (increase GFR and also NaCl - mediated by adenosine and ATP)
Vasoconstriction of efferent arteriole (also increases GFR and NaCl - mediated by RAAS)
Does angiotensin 2 preferentially work on the afferent or efferent arterioles?
Efferent
