Functions of the Kidney...
As a Homeostatic Organ:
Intake = Output
- Excretion of Metabolic Wastes
- Regulation of Volume and Composition of ECF
- Regulation of Acid-Base Balance
Function of Kidney...
As an Endocrine Organ
EPO- reg. RBC production
Calcitriol- (1,25(OH)2 - Vit. D3 - Reg. Ca and Phosphate metabolism
Renin, Bradykinins, Prostaglandins- reg. systemic and local (renal) hemodynamics- key factors in arterial hypertension
Metabolic fxns of Kindey
Key site for glycolysis, gluconeogenesis, proteolysis
Renal Blood supply is normally
20% of Cardiac Output; 99% blood flow goes to Cortex, 1% goes to Medulla
Fxnal and Structural unit of the Kidney, composed of a and its b.
a = Glomerulus
b = Tubule
Outer part of the Kidney
Most nephrons reside here
Inner part of Kidney
specialized nephrons within the Juxtamedullary have a greater concentrating ability
Filtration Occurs in the a, resorption of water mainly occurs in b.
Urine flows to a under pressure, where it is collected and transmitted to b via c, which are smooth muscle tubes.
a = renal pelvis
b = urinal bladder
c = ureters
Backflow of urine is prevented by a functional valve at a.
The Neck of the bladder has b at the conjunction with the urethra.
a = Uretero- vesicular junction
b = internal sphincter
Types of nephrons
Capillary beds in the kidney
Glomerular - under high pressure for filtering
Peritubular - situated around the tubule at low pressure
Permits large volumes of fluid to be filtered and reabsorbed
Renal A -> Interlobar Aa --> Arcuate aa --> Interlobular aa--> Afferent Arterioles --> Glomerular capillaries --> Efferent arterioles --> Vasa Recta --> Peritubular capillaries
Aff. Arterioles + Efferent + JG cells + Macula Densa
Conversion of Blood plasma into primary tubular fluid- glomerular filtrate
Occurs in the Glomerulus, through semipermeable walls of glom- caps.
Arterial Pressure provides the a necessary for filtration. It is controlled by b.
a = driving hydrostatic pressure
b = Afferent and Efferent Arterioles
Structure of Glomerular capillary wall
Creates barrier to forces favoring and opposing filtration
Capillary endothelium- single cell layer forming multiple fenestrae
Glomerular basement membrane- acellular; arranged in 3 layers
Visceral endothelium- podocytes
Forces of Filtration
Hydrostatic and Oncotic Pressure
x [( PGC
) - (∏GC
- ([ ] = Net Filtration Pressure)
- Kf = Coefficient of ultrafiltration
= Hydrostatic Pressure in Bowman's Space
= Hydrostatic P in Glomerular Cap
= Oncotic Pressure in Glomerular Capillary
= Oncotic Pressure in Bowman's Space
Mostly determines rate of filtration as well as tubular flow to renal pelvis
It is determined by the blood input from afferent arterioles and the tonus of efferents
Primary Target for mechanisms that control GFR
Plasma Oncotic Pressure increases significantly along the capillary bed due to what?
How does this affect rate of filtration?
Most of the plasma proteins are retained in the capillary lumen
Coefficient of Ultrafiltration, Kf
Selectivity of Filtration
Conferred by the selective permeability of glomerular capillary wall.
- small Cations (Na, K)
- small Anions (Cl)
Factors affecting permeability of polypeptides
Size - Smaller > Larger
Charge - Cationic polypeptides filtered more efficiently than Anionic
Shape - long, flexible proteins filtered more efficiently than Globular proteins
Regulation of GFR
Maintained within physiologic parameters by
Systemic Factors - renal modulation of systemic BP and intravascular volume
Intrinsic Factors - control of renal blood flow, PGC, and Kf.
Systemic Factors of GFR regulation
Renin- Angiotensin- Aldosterone system
Produced by JG cells in afferent arteriole
Release is stimulated by decrease in Renal Perfusion (usually from systemic hypotension)
Renin Catalyzes Angiotensinogen --> Angiotensin I
Converted from Ag-I via ACE
Ag-II is a potent vasoconstrictor acts
Directly - constr. arterial blood vessels to increase systemic BP and renal perfusion pressure
Indirectly - stimulates release of Aldosterone and ADH; both retain electrolytes and water from excretion
Negative feedback of Renin Actions
improvement of renal perfusion, and high levels of Ag-II inhibit renin release by JG cells.
Ag-II also stimulates production of Prostaglandins (PgE2 PgI2) which are vasodilators and counteract the effects of Ag-II on renal vasculature
Intrinsic factors of GFR regulation
directly control glomerular capillary perfusion
- Myogenic Reflex - Glomerular arterioles respond to changes in arteriolar wall tension; increase in tension - > constriction; decrease -> dilation
- changes regulate the resistance to blood flow in Afferent Arteriole
- reflex is independent of renal innervation
- Macula Densa (b/w afferent and efferent arterioles, and adjacent to JG cells) sense increases in Tubular Flow Rate, which leads to decrease in filtration rate of glomerulus (in same nephron)
Cx= (Ux x V)/ Px
Determination of GFR by rate of clearance of substance X from plasma
- Cx = Volume of plasma cleared cleared of substance X per unit time
- Ux = urine concentration
- V = volume urine collected over time period of collection
- Px = Plasma conc. of substance X
Inulin is indicator substance of choice because...
freely filtered by glomeruli, but neither absorbed nor secreted
it is a xenobiotic, the rate of disappearance strictly dependent on GFR
In clinical practice, most widely used indicator substance (for mammals) is...?
Filtration Fraction (FF)
Fraction of Renal Plasma Flow (RPF) that is actually filtered by glomeruli
FF = GFR/RPF
Fractional Excretion (FE)
Rate of Excretion of substance X / its rate of filtration
x V) / (Px
Used to evaluate net secretion/ reabsorption
- FE > 1, there is net secretion of indicator substance by the tubule
- FE < 1, there is net reabsorption of substance by the tubule
Renal Tubule function is assessed by determining what parameters?
FER - fractional excretion rate
FAR - fractional reabsorption rate
% of a filtered substance that is ultimately excreted in urine
FER - net result of tubular reabsorption and secretion
Proportion of filtered substance X reabsorbed by the tubule
FAR = 100% - FER
Part of Tubule Responsible for reabsorption of bulk of filtered solutes
Proximal Tubule - at least 60% of all solutes are reabsorbed here
Transport Pathways from Tubule into bloodstream
substances are taken up from tubular lumen by cells through apical membranes (brush border creates large surface area)
Active transport across cell to basolateral membrane and passed into capillaries of peritubular capillary plexus
Substances are move from tubular fluid, across Zonula Occludens, into lateral intercellular space.
Then move from here into peritubular capillaries
Substances transported via passive diffusion along [ ] gradient or by Solvent Drag.
Movement in Paracellular pathway is driven by a.
a - Starling's forces
Blood in peritubular capillaries has High Oncotic Pressure (due to loss of volume and increase [protein] ), and Low Hydrostatic Pressure (due to low resistance of their walls)
Much of the transport of substances is driven through Active Transport of Sodium mediated by...?
Na+/K+ ATPase pump in the basolateral plasma membrane.
pumps out 3 Na into Interstitial fluid and takes up 2 K into cell