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The physiology of renal system

Zaidoun Salah

AQB 20122013

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Kidney Func+on

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OVERVIEW OF STRUCTURE AND FUNCTION

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Kidneys are highly innervated and have a rich blood supply

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Kidney is designed to maintain several homeosta+c

func+ons

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Contd

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Nephron is the structural and func+onal unit of the kidney

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Three types of nephrons are classified by loca+on and architectural

design

superfecial, midcor@cal, and juxtamedullary nephrons.

Juxtamedullary nephrons differ in many ways from

other

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Juxtaglomerular apparatus is the site of renin produc+on

Te macula densa monitor the composi@on

of the fluid in the tubule lumen

Te extraglomerular mesangial cells arecon@nuous with mesangial cells of the

glomerulus; they may transmit in

forma@on from macula densa cells to

the granular cells.

The granular cells (also known asjuxtaglomerular cells) are modifed

vascular smooth muscle cells synthe

size and release renin, a proteoly@c

enzyme that results in angiotensin

forma@on

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URINE FORMATION

Tree processes are involved in forming urine: glomerular filtra@on, tubular reabsorp@on, and

tubular secre@on

Glomerular filtra+on involves the ultrafltra@on of plasma in the glomerulus. The filtrateenters the urinary space of the Bowman capsule and then flows downstream through the

tubule lumen

Tubular reabsorp+on involves the transport of substances out of tubular urine.

Reabsorbed substances include many important ions (e.g., Na+, K+, Ca2+, Mg2+, Cl, HCO3,

and phosphate), water, important metabolites (e.g., glucose and amino acids), and even some

waste products (e.g., urea and uric acid).Tubular secre+on involves the transport of substances into the tubular urine.

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Clearance is the measurement of the kidneys excre+on ability.

the renal clearance of a substance can be defined as the volume of plasma from which that

substance is completely removed (cleared) per unit @me. the clearance formula is:

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Inulin clearance equals the glomerular filtra+on rate

glomerular filtra@on rate (GFR) is the rate at which plasma is filtered by the kidney glomeruli.

A decrease in GFR generally indicates that kidney func@on is impaired

The ideal substance to measure GFR is inulin, a fructose polymer with a molecular weight of

about 5,000

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Frequency of plasma filtra@on per day

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Plasma crea+nine clearance is used clinically to es+mate GFR

IN clearance is the gold standard for measuring GFR

iothalamate

These exogenous substances must be infused intravenously and the bladder is usually

catheterized, because short urine collec@on periods are used; these procedures are

inconvenient.

poten+al drawbacks

First, crea@nine is not only filtered but also secreted by the human kidney.

The second drawback is related to errors of measuring crea@nine concentra@on in the plasma.

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Errors in es+ma+ng the cerea+nine GFR

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Plasma crea+nine concentra+on can be used to es+mate GFR

Te same rela@onssip is observed for several other substances whose excre@on depends on GFR.

For example, the plasma urea concentra@on or blood urea nitrogen rises when GFR falls. Theplasma level of a 13kDa protein molecule called cysta@n C also rises when GFR falls, and it has

been suggested that serum cysta@n C levels can be used to es@mate GFR.

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Staging of chronic kidney disease is usually based on es+mated GFR measurements; a value

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Paraaminohippurate clearance nearly equals renal plasma flow

RPF is es@mated by measuring the clearance of the organic anion pamino hippurate (PAH),

indused intravenously.

PAH is filtered and so vigorously secreted that it is nearly completely cleared from all of theplasma flowing through the kidneys.

The renal clearance of PAH, at low plasma PAH levels, approximates the RPF

where CPAH is the PAH clearance and EPAH is the extrac+on ra+o

EPAH for PAH is the difference between the arterial and renal venous plasma PAH concentra@ons

(PaPAH Prv

PAH) divided by the arterial plasma PAH concentra@on (Pa

PAH).

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The PAH is supplied to the kidneys in the arterial plasma and leaves the kidneys in urine and

renal venous plasma, or:

Contd

If we assume extrac+on of PAH is 100% (EPAH = 1.00), then the RPF equals the PAH clearance

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Net tubular reabsorp+on or secre+on of a substance can be calculated

from altered and excreted amounts

The rate at which the kidney tubules reabsorb a substance can be calculated if we know howmuch is filtered and how much is excreted per unit @me.

In equa@ons 8 and 9, we assume that substance X is freely filterable.

For example, about 40% of plasma Ca2+ is bound to plasma proteins, and so 60% of plasma

Ca2+ is freely filterable.

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Renal glucose reabsorp+on retrieves filtered glucose and prevents

glucose loss in the urine

The glucose threshold is not fixed but depends on:

1.

GFR :low GFR leads to higher threshold2. TmG: when reduced, reduces the threshold3. amount of splay: Reasond for splay includes:a. Not all the nephrons have the same filtra@on

and absorp@ve capaci@es

b. The glucose carriers dont have infinite affinityfor glucose, so glucose might be excreted even

before carriers become saturatedAn increase in splay causes a decrease in glucose

threshold

In uncontrolled diabetes mellitus a lot of glucose is excreted and results in glucosuria that

produces an osmo@c diuresis

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Tm for PAH provides a measure of func+onal proximal secretory +ssue

PAH is secreted only by proximal tubules in the kidneys.