Second diagram shows blood flow rates (in mL/min per gram tissue)
* At the corticomeduallary junction the interlobar gives off branches knows as arcuate arteries
Functions of mesangial cells: supportive to glomerular capillaries, secret extracellular matrix, phagocytosis, secrete PGs & proinflammatory cytokines. Also have contractile properties – may infleunce GFR by regulating blood flow. Extraglomerular mesangial cells are mesangial cells located out glomerulus, b/w afferent and efferent arteriole.
A, Scanning electron micrograph showing the outer surface of glomerular capillaries. B, Scanning electron micrograph of the inner surface (blood side) of a glomerular capillary. Processes (P) of podocytesCell body (CB)
TF/Px=1 at glomerulus since no reabsorption takes placeFiltration barrierCapillary endothelium Capillary BMFoot processes of podocytes
One of the highest blood flows in the body – only seconded by pituitary and carotid sinuses
Ap = systemic BPRe = efferent art. ResistanceRa = afferent art. Resistance chronic, uncontrolled hypertension and DM gradually reduce Kf by increasing the thickness of the glomerular capillary basement membrane and, eventually, by damaging the capillaries so severely that there is loss of capillary function.
Equation-I: When used for GFR estimation – RPF will be ignored since we can concentrating on filtration fn of kidney When RPF estimation – it will be solved for RPF!
Student should ask about Urine flow rate = 1 ml/min
*Hence inulin can ONLY be used to estimate GFR NOT RPF
BODY FLUIDS & KIDNEY Dr. Faraz Bokhari
“It is no exaggeration to say that the composition of the blood is determined not so much by what the mouth takes in as by what the kidneys keep” ■ Homer Smith
Functions of Kidneys• Multiple functions • Excretion of metabolic waste products and foreign chemicals • Regulation of water and electrolyte balances • Regulation of body fluid osmolality and electrolyte concentrations • Regulation of arterial pressure • Regulation of acid-base balance • Secretion, metabolism, and excretion of hormones • Gluconeogenesis
Nephron: Functional Anatomy• Fenestration: 70-90 nm (diameter)• Filtration slits: 25 nm (diameter)• Glomerular membrane permits • Free passage of neutral substances up to 4 nm • Excludes more than 8 nm diameter molecules • Freely permeable to water, small solutes such as sodium, urea, and glucose • TF/Px*• Glomerular capillary bed is unique • High hydrostatic pressure (55-60 mmHg) • Filtration only • Permeability 100x more • Double membrane system
Glomerular Filtration Rate (GFR)• Amount of filtrate formed by ALL nephrons of both kidneys per minute • Mean value: 125 ml/min• GFR = Kf [(PGC – PT) – ( GC - T)]• GFR = Kf x NFP – Kf : Filtration Coefficient » (Glomerular cap. permeability x Effective filtration surface area) » Kf = GFR/NFP = 12.5 ml/min/mm Hg
Factors Affecting GFR – Overview• Renal Blood Flow (RBF)• Changes in Starling Forces & Glomerular capillary coefficient (Kf)
Renal Blood Flow (RBF)• RBF is very high • 1.25 L/min or 1800 L/day (~20% C.O.)* • Kidneys use about 8% of total resting O2 – Kidneys heavy blood flow carries much more O2 than required – Hence much of the O2 is unused – Still kidneys are sensitive to ischemic damage – WHY? • RBF = Aortic P – Renal Venous P/Renal Vascular resistance
Renal Blood Flow (RBF)• RBF and GFR are co-regulated • Changing BP (80-180 mmHg) induces autoregulation – Intrinsic • Autoregulation – Myogenic* – Tubuloglomerular feedback (TGF) – Glomerulotubular feedback • Local hormones – Extrinsic • Nerves • Blood-borne hormones
RBF Autoregulation: Myogenic• Observe ‘autoregulation’ in Aff/Eff vessels (top graph) as BP changes – Myogenic response!!• Observe constant RBF & GFR in BP fluctutation b/w 80-180 mmHg
• Fick’s Principle of Mass Conservation• Concept of Clearance – GFR estimation – RPF & RBF estimation
CLEARANCE• “Volume of plasma that is cleared of a substance by kidneys per unit time is the clearance of that substance” • Useful way of quantifying renal excretory function• Based on Fick’s Principle of Mass Balance • (Pxa x RPFa) = (Pxv x RPFv) + (Ux x V) - I • We are concerned with excretory function of kidney only • Hence concept of renal clearance relates to: – What comes in via renal artery (Pxa) – What is excreted via urine (Ux x V) » (renal vein calculations will be considered in certain scenarios e.g. when calculating RPF)
CLEARANCE• Hence equation-I b/c: • (Pxa x RPFa) = (Pxv x RPFv) + (Ux x V) –I – Since our emphasis is on filtration only, • Pxa ∞ (Ux x V) – II – Substance x in plasma and its conc. in urine is linked by rate @ which it is removed from plasma and ‘put’ in urine – clearance • Pxa x Cx = (Ux x V) – III • Cx = Ux x V/ Pxa – IV
EXAMPLE• Example: Substance ‘A’ – Plasma conc. of ‘A’ = 1 mg/ml – Conc. of ‘A’ in urine/min = 1 mg/min – Clearance of ‘A’ = ?
GFR Estimation• Can we use concept of Clearance to estimate GFR?• Remember: • Clinically GFR measurement has prognostic value • Quality of substance used for GFR measurement » Freely filterable at glomeruli » Neither reabsorbed nor secreted » Not metabolized by body » Non-toxic » Does not alter GFR • Only ~20% of total RPF b/c GFR*
GFR Measurement• Inulin [IN] - fructose polymer, is used in GFR measurement – Loading dose of Inulin I/V – Equilibration with body fluids – Timed urine specimen – Plasma sample – Creatinine (Cr) clearance is also used – Source of plasma creatinine is the normal metabolism of creatine phosphate in muscle – Value of U x V is high – tubular secretion – Value of P is also high – detection of Cr is not highly sensitive – value includes other proteins – The two errors cancel out each other!
RPF/RBF Measurement• Clearance of PAH » PAH is filtered/secreted (very high extraction ratio) » Renal Plasma Flow (effective renal plasma flow)– ERPF » PAH is 90% cleared from circulation in a single circulation through kidney – True Vs Effective RPF• Renal Blood Flow (RBF) estimation » Renal Blood Flow = RPF /(1-Hct) » Hct = 45% » RBF = RPF x 1/1- Hct = 1273 ml/min
Filtration Fraction/ Extraction Ratio• Filtration fraction • GFR/RPF • 20% plasma flowing through kidneys is filtered • Value: 0.16 – 0.2 (~ 20%)• Extraction ratio • Renal Art. Conc. – Renal venous conc./ art. Conc. • PAH has a very high extraction ratio
Other Formulae• QUANTIFYING filtration, secretion, reabsorption and net excretion – Filtration load – GFR x Px – Excretion rate – V x Ux – Fractional excretion (FE) – Excretion rate/filtration load » What does it mean if: » FE > 1 » FE < 1 » FE = zero!