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

Renal Anatomy

• 2 kidneys: posterior wall of abdomen,

outside peritoneal cavity• Hilum• Capsule• Outer region: Cortex • Inner region: Medulla• Renal pyramids

Nephrons

• Each human kidney – about 1 million nephrons– Cortical

nephrons (85%)– Juxtamedullary

nephrons

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

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)

RENAL CORPUSCLE & JUXTAGLOMERULAR APPARATUS

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) – (ּתGC - ּתT)]• 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

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

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

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

Starling Forces at Glomerulus also affect GFR

Changes in Starling Forces & Kf

• 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• (Px

a 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:• (Px

a x RPFa) = (Pxv x RPFv) + (Ux x V) – I

– Since our emphasis is on filtration only,• Px

a ∞ (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• Px

a x Cx = (Ux x V) – III• Cx = Ux x V/ Px

a – 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

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)

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!