Stokes - Kidney Structure and Function

8/12/2019 Stokes - Kidney Structure and Function

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The Kidney: Physiology,Function

and Assessment of Function

Felicity StokesSenior Clinical Biochemist

Department of Clinical Chemistry and Metabolic MedicineRoyal Liverpool and Broadgreen University Hospitals


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Overview of talk

Review of kidney structure Review of kidney function

Tests for assessment of kidney function


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Gross anatomy of kidneys Located in the retroperitoneal space The right kidney is situated slightly lower than the left Adult kidneys:

~ 12cm long weigh 135g in women and 150g in men Adrenal glands located just above kidneys


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Renal Blood Supply

Very important that the kidneys have a goodblood supply for their functions Receives ~ 25% of cardiac output

Aorta

afferent arteriolesefferent arterioles

renal venules

renal veins

inferior vena cava

renal artery

A complex array of regulatory

mechanisms ensure that the bloodflow to the kidneys is maintainedacross a range of blood pressures.


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Urinary Tract Filtered toxins and water leave each kidney

though the ureter Each ureter drains into the urinary bladder Urine is then excreted through the urethra

Kidney

Ureter

Bladder

Urethra


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Excretion of waste products of protein metabolism

Water and electrolyte homeostasis

Acid base homeostasis

Main Function of Kidneys

Endocrine Functions Production of renin Activation of Vitamin D Production of erythropoietin

Creatinine Urea

Excretion of H +Regeneration of bicarbonate

Sodium

PotassiumChloride

Carried out by filtering the blood and excreting what is not wanted in theurine, while reabsorbing everything that is useful back into the body

Water


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The nephron Glomerulus Proximal convoluted tubule Loop of Henle descending limb

ascending limb Distal convoluted tubule Collecting duct


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The glomerulusWhere the blood is filtered to maintain importantconstituents like blood cells in the blood butremove fluid, waste products and regulate H +, Na + and K + concentrations

Blood is separated from the lumen of thenephron by 3 layers that filter it:

Capillary endothelial cells

Glomerular basement membrane

Podocytes of glomerular epithelium


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Capillary vascular space

Glomerulus lumen

Basement membrane

Endothelial cells

Slit pores

Fenestrations

Na +

Cl-

K+

K+

K+Na +

Cl-

Cl-

Na +

Na +

Low MW proteins andelectrolytes

Cells and largeMW proteins

Podocytes

with footprocesses


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Glomerular Filtrate An ultrafiltrate of the blood enters the lumen

of the glomerulus Composition similar to plasma except blood

cells and molecules of protein > 50 kDa areabsent

Molecules around the size of albumin(68kDa) and larger are prevented from

entering lumen Proteins prevented according to charge as

well as size (more negatively chargedproteins retained in blood)


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Proximal convoluted tubule

Carries out most of the reabsorptionof electrolytes from the filtrate backinto circulation

75% of sodium and chloride Water (follows sodium and chloride

passively by osmolality)

Almost all bicarbonate , calcium ,potassium, glucose and aminoacids


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Loop of Henle Has a descending limb and ascending limb Not all nephrons have a loop of Henle

Extends from the cortex downinto the medulla and back upagain

Thick ascending limb isimpermeable to water

It is responsible for creating ahyperosmolar medulla

This is necessary for theproduction of a concentrated urine


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Counter-current system Ascending loop of Henle reabsorbs 25% of sodium/chloride

These diffuse through the interstitial space and some diffuseback into the descending limb. (flow back into ascendinglimb)

No water follows them as it is impermeable to water

This alters the osmolality of the fluid inthe nephron and in the surroundinginterstitial space of the medulla

Causes a gradient of osmolality to be

created with the osmolality increasingwith deep down into the medulla

Causes water to diffuse out of thedescending limb into the hyperosmoticmedulla


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Counter-current system (2) The vasa recta capillary plays animportant role in this process by quickly

removing any water that is reabsorbedfrom the descending limb

This maintains the high osmolality

The result is a fluid that is hypotoniccompared to the plasma going in to thedistal convoluted tubule

The dilute fluid enters the distalconvoluted tubule and collecting duct,where water can be reabsorbed bypassive diffusion down theconcentration gradient by the medullaryhyperosmolality that has been created


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Distal Convoluted Tubule

Carrries out the fine -tuning ofelectrolyte reabsorption or excretion

Specifically Na +, K+, H + Affected by concentration of these in

plasma to carry out homeostasis Under hormonal control (Aldosterone)


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Distal Convoluted Tubule

Na +

K+ or H +

Lumen

Tubularcell

Aldosterone


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Collecting duct Carries out the reabsorption of water

Naturally impermeable to water

Passive diffusion under the control of osmolar differencebetween tubular cells and lumen (created by counter-current

system of Loop of Henle)

ADH

If there is a need toconserve water:

ADH is stimulated

Causes aquaporinswater transportersto move to theimpermeablemembrane to allowwater to passthrough


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Summary of nephron

Glomerulus filters blood Proximal tubule bulk reabsorption

Loop of Henle production of osmosticgradient for control of waterreabsorption

Distal tuble fine tuning of reabsorption Collecting duct water reabsorption (orexcretion)


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Assessment of renal function Main function of kidneys is to clear waste

products from the plasma This is used to assess and monitor renal

function Creatinine produced at a constant rate by

skeletal muscle cells Not really affected by other factors very

little reabsorption or secretion in renaltubules

Can measure its clearance from plasma orexcretion in urine


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Glomerular Filtration Rate (GFR)

Kidneys usually filter ~170L of water each day(120 mL/min)

Affected by: Number of nephrons

Blood supply to the nephron Integrity of the glomerulus

These can be altered in disease and affect the GFR

The volume of plasma that is filtered by the kidneysand from which a substance is completely clearedper unit of time


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Assessment of Renal Function

Serum Creatinine 1 blood sample convenient, cheap, quick BUT - not sensitive

Serum creatinine onlystarts to increase abovenormal when the kidneyia at about half functionwith a GFR of~60mL/min

A small person with alow muscle mass willhas a much lowerserum creatinine

A bodybuilder willhave a muchhigher serum

creatinine

AND affected by muscle mass
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Assessment of Renal Function

Creatinine Clearance Used to calculate Glomerular Filtration Rate

More sensitive at picking up small changes in renalfunction

BUT 24 hr urine collection plus serum required Inconvenient, lots of measurements and calculation =

lots of room for error!

Clearance = U x V

P

[Urine Creatinine (umol/L)] x Urine Volume (mL) = mL/min[Plasma Creatinine (umol/L)] x Collection period (min)

U = Urine concentration

V = VolumeP = Plasma concentration


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Assessment of Renal Function eGFR (estimated GFR) Uses serum creatinine to estimate GFR

More sensitive than creatinine Uses only serum creatinine measurement and a

calculation, therefore only 1 blood samplerequired more convenient

BUT not to be used in certain situations such asacute illness, pregnancy, young and elderly

As it uses serum creatinine in its formula, stillaffects by variations in muscle mass


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eGFR Various equations exist

Based on large scale studies that measured GFR or Cr Cl bygold standard methods and serum creatinine and worked outa formula to calculate these

Built in several other factors that affect serum creatininemeasurement age, sex, ethnicity, weight

Cockcroft-Gault

MDRD widely accepted and used as the best formula for estimating GFR

GFR (mL/min/1.72m 2) = 175 x [serum creatinine (umol/L) x 0.011312] -1.154 x (age) -0.203

x 0.742 if female

x 1.210 if African American4 variables serum creatinine, age,sex, ethnicity

Cr Cl (mL/min) = [(140 age) x weight/0.814 x serum creatinine (umol/L)]

x 0.85 if female


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Limitations of eGFR

Serum Creatinine = 40 umol/L Serum Creatinine = 180 umol/LSerum Creatinine = 110 umol/L

Calculated eGFR =>90 mL/min/1.73m 2

Calculated eGFR =66 mL/min/1.73m 2

Calculated eGFR =37 mL/min/1.73m 2

Actual GFR = 45mL/min/1.73m 2

Actual GFR = 66mL/min/1.73m 2

Actual GFR = >90mL/min/1.73m 2


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Specialist tests for GFR In some situations, a very accurate GFR may be needed

Or in children, where MDRD equation is not validated Exogenous markers

Inulin clearance = Gold standard measure of GFR Infusion of inulin and urinary clearance Collect blood and urine samples

Gold Standard measure of GFR51 Cr-EDTA = standard clinical measure of GFR

Injection bolus of 51Cr-EDTA Collect blood samples Calculate eGFR from known amount injected and the decrease

in activity over time

Endogenous markersCystatin C

Protein produced by all nucleated cells More specific than creatinine But assay = expensive


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Other tests for assessment ofkidney function

U&Es CAPR

Urine analysis

Urine dipsticks Urine proteins

Protein - proteinuria

Blood - haematuria


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Proteinuria (2) In kidney disease, these can go wrong andincreased levels of protein are seen in urine

Damaged to glomerulus can cause large proteinsor blood cells to leak through

Damage to the tubules can cause proteins (andother things such as K + not be reabsorbed)

Proteinuria assessed by: Urine dipsticks ACR Albumin:creatinine ratio PCR Protein:creatinine ratio Total protein/ 24 hrs


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Proteinuria (3)

ACR = Albumin Creatinine Ratio Random urine sample Differences in concentration are corrected

for by measuring Creatinine

PCR = Protein Creatinine Ratio

ACR more sensitive as measuring albumin which isonly JUST excluded by glomerulus

Also more standardised as a specific method Measured in ALL diabetics on an annual basis to

screen for early signs of kidney disease

ACR = Urine AlbuminUrine Creatinine

PCR = Urine Total proteinUrine Creatinine


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Summary Physiology & Function

Kidneys filter the blood to excrete toxins such as ureaand creatinine while altering reabsorption and excretionof sodium, potassium, water to regulate their balance

They also play a role in acid-base homeostasis

Kidneys also: Activate vitamin D (by 1 -hydroxylase)] Synthesize and secrete renin Synthesize and secrete erythropoietin

The kidneys contain ~1 millions functional units callednephrons

These have a glomerulus, proximal convoluted tubule,loop of Henle, distal convoluted tubule and collectingduct


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Summary - Assessment

Excretion of creatinine: Creatinine clearance eGFR

Urea and Electrolytes: Raised K +

Raised Urea and Creatinine

Proteinuria Dipsticks PCR, ACR 24 hr urine protein


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References

Clinical Biochemistry An illustratedcolour text by Allan Gaw

Clinical Chemistry by Marshall & Bangert Little Marshall

ACB Publication: Kidney Diseasae andLaboratory Medicine by Edmund Lamb &Michael Delaney


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Stokes - Kidney Structure and Function

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