Physiology

Intake = Output

• Excretion of Metabolic Wastes
• Regulation of Volume and Composition of ECF
• Regulation of Acid-Base Balance

Production of:

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

Key site for glycolysis, gluconeogenesis, proteolysis

20% of Cardiac Output; 99% blood flow goes to Cortex, 1% goes to Medulla

Nephron

a = Glomerulus

b = Tubule

Cortex

Most nephrons reside here

Medulla

specialized nephrons within the Juxtamedullary have a greater concentrating ability

a= Cortex

b= Medulla

a = renal pelvis

b = urinal bladder

c = ureters

a = Uretero- vesicular junction

b = internal sphincter

Cortical

juxtamedullary

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.

a = driving hydrostatic pressure

b = Afferent and Efferent Arterioles

Capillary endothelium- single cell layer forming multiple fenestrae

Glomerular basement membrane- acellular; arranged in 3 layers

Visceral endothelium- podocytes

Hydrostatic and Oncotic Pressure

K_f x [( P_GC - P_BS) - (∏_GC - ∏_BS)]

• ([ ] = Net Filtration Pressure)
• K_f = Coefficient of ultrafiltration

P_BS = Hydrostatic Pressure in Bowman's Space

P_GC = Hydrostatic P in Glomerular Cap


∏_GC = Oncotic Pressure in Glomerular Capillary

∏_BS = 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

Most of the plasma proteins are retained in the capillary lumen

Coefficient of Ultrafiltration, K_f

Conferred by the selective permeability of glomerular capillary wall.

• Water
• small Cations (Na, K)
• small Anions (Cl)
• Glucose

Proteins

Size - Smaller > Larger

Charge - Cationic polypeptides filtered more efficiently than Anionic

Shape - long, flexible proteins filtered more efficiently than Globular proteins

Maintained within physiologic parameters by

Systemic Factors - renal modulation of systemic BP and intravascular volume

Intrinsic Factors - control of renal blood flow, P_GC, and Kf.

Mostly Humoral

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

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

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

Tubulo-glomerular Feedback - 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)

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

freely filtered by glomeruli, but neither absorbed nor secreted

it is a xenobiotic, the rate of disappearance strictly dependent on GFR

Creatinine

Fraction of Renal Plasma Flow (RPF) that is actually filtered by glomeruli

FF = GFR/RPF

Rate of Excretion of substance X / its rate of filtration

FE_x = (U_x x V) / (P_x x GFR)

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

FER - fractional excretion rate

FAR - fractional reabsorption rate

FER - net result of tubular reabsorption and secretion

FAR = 100% - FER

Proximal Tubule - at least 60% of all solutes are reabsorbed here

Transcellular

Paracellular

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.

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)

Na⁺/K⁺ ATPase pump in the basolateral plasma membrane.

pumps out 3 Na into Interstitial fluid and takes up 2 K into cell