Structure and function of kidney
The main function of the kidneys is to regulate the volume and composition of the
extracellular fluid. This is done with filtration, absorption and secretion.
The processes of filtration, absorption and secretion are regulated
homeostatically so as to minimize changes in extracellular fluid composition
Other functions
Excrete metabolic waste products including creatinine, urea, uric acid and some
end products of haemoglobin breakdown
Excrete foreign substances and their derivatives, including drugs, and food
additives such substances are therefore excreted less efficiently when kidney
function is impaired
ynthesize prostaglandins and kinins that act within the kidney
!unction as endocrine organs, producing the hormones renin, erythropoietin
and calcitriol, the active form of vitamin "
In the glomerulus, the filtrate of plasma has to pass through three layers:
The fenestrated #perforated$ from the %atin fenestra a window& endothelium of
the capillary which is the filtering membrane.
The basement membrane of the 'owman(s capsule which is mainly composed
of connective tissue, but also contains mesangial cells that are both phagocytic
and contractile. 'y contracting they are thought to be able to actively reduce
glomerular filtration by reducing the area available for filtration.
The epithelial cells of the capsule. These are known as podocytes because they
)ave numerous foot*like pro+ections #pedicels& that clasp the tubes of capillary
endothelium. ubstances that pass through the filtration slits #or pores&
between the pedicels therefore pass close to the cell surface of the podocytes
Structure of the tubule
The epithelial cells of the proximal tubules contain many mitochondria and have
many microvilli at their luminal surface, called a brush border, which increase the
surface area #!ig. ,.-..&. /d+acent cells are +oined together at their luminal
#apical& ends by tight +unctions #see p. 01&. /t their basal ends, there are gaps
between them, known as lateral intercellular spaces.
The descending limb of the loop of )enle and the first part of the ascending limb
are thin walled2 the epithelial cells contain relatively few mitochondria and are
flattened with few microvilli. The ascending limb becomes thick walled as it
enters the cortex$ there are many mitochondria and microvilli, but fewer than in
the proximal tubule. /long the length of the distal tubule and collecting ducts, the
numbers of mitochondria and microvilli decrease. 3n the late part of the distal
tubule and collecting duct there are two specialized types of cells #principal and
intercalated& that are involved in 4a565 balance and )5 balance #see 7h. ,.8&.
3n the glomeruli, blood is exposed to a filtering membrane of about - m9 in area,
e:ual to over half of the external surface of the body.
The filtration barrier only allows substances of up to a molecular weight of -1 111
to pass freely. %arger molecules are increasingly restricted, those of molecular
weight of -11 111 and above usually being unable to pass through at all. /n
additional barrier is formed by fixed negative charges, probably on the basement
membrane but possibly on the podocyte cell membrane as well, which repel
negatively charged anions. Thus, haemoglobin from lysed red blood cells
passes into the tubule far more easily than albumin, even though they both have
a molecular weight of about ;1 111, simply because albumin has more negative
charges.
!iltration of a substance depend on
<olecular size
7harge of the substance
'inding to plasma proteins # e.g. Thyroxine ,7alcium, and free fatty acids &
Glomerular filtration rate
=lomerular filtration rate is determined by the difference between the hydrostatic
pressure and osmotic pressures in the glomerular capillaries and in the lumen of
the 'owman(s capsule
The hydrostatic pressure in the glomerular capillary is higher than in other
capillaries in the body because2
renal afferent arterioles are usually wider than most other arterioles and offer
less resistance
renal efferent arterioles offer a substantial postcapillary resistance.
Measurement of GFR
=!> is not measured directly, but by measurement of the excretion of a marker
substance. 3f a substance has the same concentration in the glomerular filtrate as
in plasma and if that substance is neither added to the urine nor taken away
from it by the tubules, then the amount of that substance filtered per minute
must e:ual the amount excreted per minute2
?@ A =!> B C@ A D
where ?@ and C@ are the concentrations of the substance, @, in plasma and
urine respectively and D is urine flow as a volume per unit time.
Therefore
=!> B C@ A D
. ?@
=!> can be measured by using inulin, a polymer of fructose, which is freely
filtered and neither secreted nor reabsorbed by the nephron.
3nulin does not occur naturally in the body and must be given as a continuous
intravenous infusionto achieve a constant plasma concentration.
3n an average human adult, =!> is approximately -9. mlEmin #-,1 lE98 h&. /s the
total volume of plasma is about F litres, the entire plasma volume is filtered about
01 times every 98 hours.
7linically, creatinine is often used for the measurement of =!>. 3t is naturally
occurring and is released into plasma at a fairly constant rate by skeletal muscle.
Therefore there is no need to give an infusion. /lthough it is freely filtered, some
additional creatinine is secreted by the nephron. )owever, the methods available
for measuring creatine concentration tend to overestimate its concentration in
plasma.Thus, the errors tend to cancel out and =!> values estimated with
creatinine agree well with those measured with inulin.
If a substance has a clearance greater than that of inulin, then it must have
been secreted into the tubular fluid by the nephron epithelium If it has a
clearance lo!er than that of inulin, either it !as not filtered freely at the
glomerulus, or it must have been reabsorbed from the tubular fluid