The kidneys have multiple important functions including excretion of waste, regulation of fluid and electrolyte balance, and hormone regulation. The basic functional unit of the kidney is the nephron, which filters blood in the glomerulus and reabsorbs and secretes substances along the tubule. Precise regulation of blood flow and filtration allow the kidneys to maintain homeostasis. Glomerular filtration rate and clearance concepts are used to measure kidney function.

1. BODY FLUIDS & KIDNEY
Dr. Faraz Bokhari

2. “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

3. 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

4. Renal Anatomy
• 2 kidneys: posterior wall of
abdomen,
outside peritoneal cavity
• Hilum
• Capsule
• Outer region: Cortex
• Inner region: Medulla
• Renal pyramids

5. Nephrons
• Each human
kidney – about 1
million nephrons
– Cortical
nephrons (85%)
– Juxtamedullary
nephrons

6. Blood & Nerve Supply
• Renal A – Segmental As – Interlobar As – Arcuate As*
– Cortical Radial As
• Afferent arterioles – Glomerulus – Efferent arteriole
• Efferent arteriole:
– Source of blood supply to medulla
– Forms peritubular capillary network
– Vasa recta
• Kidney is richly supplied by sympathetic nerve fibers
– Renal blood vessels vasoconstriction
– Increased Na+ reabsorption by tubular cells
– Increased renin secretion

7. Nephron: Functional Anatomy
• Two components:
• Renal corpuscle
– Glomerulus
– Mesengium
– Bowman’s space & capsule
• Long tubule
• Glomerulus
» 200 micrometers (diameter)
» Invagination of a tuft of capillaries into blind Bowman’s capsule
» Afferent arteriole & Efferent arteriole
» Podocytes (in between capillaries outside their basal lamina)
» Mesangial cells (between basal lamina and endothelium)

8. RENAL CORPUSCLE & JUXTAGLOMERULAR APPARATUS

12. 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

13. 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

14. Factors Affecting GFR –
Overview
• Renal Blood Flow (RBF)
• Changes in Starling Forces & Glomerular
capillary coefficient (Kf)

15. 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

16. 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

17. 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

18. RBF Autoregulation: T-G Balance
• T-G Balance includes:
• (1) Afferent arteriolar
feedback mechanism
• (2) Efferent arteriolar
feedback mechanism
• Summary of renin
secretion:
– Renal Perfusion
Pressure
– Sympathetic +
– By macula densa
feedback

19. Renal Blood Flow (RBF)
– Extrinsic factors
• Sympathetic stimulation
» Vasoconst. Of interlobular and afferent arterioles
• Angiotensin II
– Potent vasoconstrictor
» Small conc. – efferent art. Constriction (GFR raised)
» Moderate to high conc. – afferent & efferent art.
Constriction (GFR decreased)
• Vasodilators
» NO, ANP, cAMP, PGI2, high protein diet
• Vasodilators
» Thromboxane A2, Adenosine, angiotensin-II, PGE2

20. About AUTOREGULATION
• It is absent below 90 mmHg
• Not perfect; RBF, GFR do change slightly with
changing BP
• Even while being autoregulated, various
hormones can change RBF, GFR

21. Starling Forces at Glomerulus also affect GFR

22. Changes in Starling Forces & Kf

23. • Fick’s Principle of Mass Conservation
• Concept of Clearance
– GFR estimation
– RPF & RBF estimation

24. 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)

25. 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

26. EXAMPLE
• Example: Substance ‘A’
– Plasma conc. of ‘A’ = 1 mg/ml
– Conc. of ‘A’ in urine/min = 1 mg/min
– Clearance of ‘A’ = ?

27. 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*

29. 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!

30. 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

31. 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

32. Values To Remember
• GFR: 125 ml/min (180 L/day)
• RPF: 600 ml/min
» Actual RPF = 700 ml/min
» Effective RPF = 630 ml/min
• RBF: 1100 ml/min
• Urine flow rate: 1 ml/min
• Filtration fraction: ~20% (0.16 - 0.2)

33. 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!