Body fluids and

Renal physiology

By: Dr. FoadoddiniDepartment of Physiology & PharmacologyBirjand University of Medical Sciences

25

Volume and Osmolality of Extracellular and Intracellular Fluids in Abnormal States

Fluids in the "Potential Spaces" of the Body

Edema

Pc

Kf πC

Safety factor

Low compliance in IF

3 mmHg

"Washdown“of IF  Protein

7mmHg

LymphFlow

7mmHg

Safety Factors That Normally Prevent Edema

26

Blood Supply to the Kidneys• Blood travels from afferent arteriole to capillaries in the nephron called glomerulus • Blood leaves the nephron via the efferent arteriole• Blood travels from efferent arteriole to peritubular capillaries and vasa recta

Internal Anatomy

• Blood is filtered in the nephrons

• The cortex of each kidney contains ± 1,2 million nephrons

• The nephron consists of a renal corpuscle and a renal tubule

• The renal tubule consists of the convoluted tubule and the loop of Henle

• The main filter of the nephron is glomerulus which is located within the Bowman's capsule

Function of the Kidney• Terminology

Micturation

Bowman’s capsules - with glomerulus

The filtration barrier - podocytes

fenestratedendothelium

fenestratedendothelium

primaryprocess

podocytecell bodysecondary

process(pedicel)

filtrationslit

basallamina

podocyte

pedicel filtration slitbasal

lamina

Detailed structure of the filtration system

Capillary

CapillaryBasementmembrane

Basementmembrane

Fenestrations

Fenestrations

Podocyte process

Capillary

BM

Endothcell nucleus

Endothcell nucleus

E

F

The filtration barrier - pedicels

Bowman’s space

capillary

pedicel

filtration slit

Control of Kf• Mesangial cells have contractile properties, influence capillary 

filtration by closing some of the capillaries – effects surface area

• Podocytes change size of filtration slits

GLOMERULAR FILTRATION

The first step in the formation of urine is the production of a plasma ultrafiltrate.The ultrafiltrate is cell and protein-free and the concentration of small solutes are

the same as in plasma.The filtration barrier restricts movement of solutes on a basis of size and charge. Molecules < 1.8 nm freely filtered; >3.6 nm not filteredCations are more readily filtered than anions for the same molecular radius.Serum albumin has a radius if about 3.5 nm but its negative charge prevents its

filtration

In many disease processes the negative charge on the filtration barrier is lost so that proteins are more readily filtered - a condition called proteinuria

The glomerular filtration rate (GFR) is about 125 ml/min in a normal adult

10mmHg

Glomerular hydrostatic pressure, PGC, is high and relatively constant ≈45 mmHg.This is offset by a pressure in Bowman’s capsule PBC ≈10 mm Hg

Net filtrative force is:≈ 35 mm Hg

PGC-PBC40

30

20

10

0

mm Hg

aff. art eff. art.

THE GLOMERULUS - THE STARLING EQUILIBRIUM

The glomerulus is unusual with respect to most capillary beds.

Glomerular hydrostatic pressure, PGC, is high and constant ≈45 mmHg.This is offset by a pressure in Bowman’s capsule PBC ≈10mmHgNet filtrative force is:≈ 35 mm Hg

Osmotic pressure, ΠGS, ≈25 mm Hg.Due to the large net filtration of fluid ΠGS increases along the capillary to 35

mm Hg to achieve a balance of forces.

PGC-PBC40

30

20

10

0

mm Hg

Net filtrationforce

ΠGS

THE GLOMERULUS - THE STARLING EQUILIBRIUM

aff. art eff. art.

FILTRATION FRACTION

Filtration fraction is an important expression of the extent of glomerular filtration.

It is the ratio: Filtration fraction = Glomerular filtration rate

Renal plasma flow

It is the fraction of renal plasma flow that is filtered at the glomerulus

RPF750 ml/min

GFR125 ml/min

Renal blood flow1250 ml/min

EfferentArteriole

625 ml/min

Urine 1 ml/min

124 ml/min

renal

vein

glomerulus

tubule

Thus, in this example filtration fraction is: 125750 ≈ 0.17

GFR and RPF can be measured separately using clearance methods

Glomerular filtration rate (GFR)is about: 125 ml/min

Renal blood flowis about: 1250 ml/min

Renal plasma flow (RPF)is about: 750 ml/min

FILTRATION FRACTIONan example

Remember: plasma volume is about 60% of total blood volume

RENAL BLOOD FLOW (RBF)

Renal blood flow is ≈1.25 l/min -i.e. about 25% of the cardiac outputThis is a very large flow relative to the weight of the kidneys (≈350 g)

Renal blood flow

GFR

0 100 200

Arterial blood pressure, mm Hg

1.5

1.0

0.5

0

Flow, l/minRBF determines GFR

RBF also modifies solute and water reabsorption and delivers nutrients to nephron cells.

Renal blood flow is autoregulatedbetween 90 and 180 mm Hg by varying renal vascular resistance (RVR)

i.e. the resistances of the interlobular artery, afferent arteriole and efferent arteriole

RENAL BLOOD FLOW - AUTOREGULATION

Two hypotheses have been proposed to explain autoregulation

1. Myogenic hypothesisWhen arterial pressure increases the renal afferent arteriole is stretched

Autoregulation effectively uncouples renal function from arterial blood pressure and ensures that fluid and solute excretion is constant.

Increase of arterial pressure

Flow increases

Remember:

Flow α 1r4

RENAL BLOOD FLOW - AUTOREGULATION

1. Myogenic hypothesisWhen arterial pressure increases the renal afferent arteriole is stretched

Vascular smooth muscle responds by contracting thus increasing resistance

Increase of arterial pressure

Increase of vascular tone

Flow increases

Flow returns to normal

RENAL BLOOD FLOW - AUTOREGULATION

2. Tubuloglomerular feedback

Alteration of tubular flow (or a factor in the filtrate) is sensed by the macula densa of the juxtaglomerular apparatus (JGA) and produces a signal that alters GFR.

It is unclear what is the factor (NaCl reabsorption?) or the nature of the signal (renin?).

4. ↑Ra↓GFR

1. ↑GFR

2. ↑filtrate

3.signal from JGA

27: Tubular Processing of theGlomerular Filtrate

10mmHg

First Defense line: TGF GFR regulation

Second Defanse line: GTB Reabsorption regulation

ΔP ΔUOAgII

Use of ClearanceMethods to Quantify Kidney Function

C = U * V/ P

GFR = Cinulin FF=  GFR / RPF

RPF= CPAH