AORN A.CARDARELLI NAPOLI dr.E.Di Florio III Water and electrolyte balance • Acid/Base status...
Transcript of AORN A.CARDARELLI NAPOLI dr.E.Di Florio III Water and electrolyte balance • Acid/Base status...
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AORN A.CARDARELLI NAPOLIdr.E.Di Florio III SAR
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Renal Anatomy
Cortex
Medulla
Pelvisof theureter
To the bladder
Capsule
Ureter
Renal Artery& Veins
Medulary Pyramid
11cm
6 cm3cm
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Renal Anatomy and Physiology
• pair of fist-sized organs located on either side of the spinal column just behind the lower abdomen (L1-3).
• Consists of an outer layer (renal cortex) and an inner region (renal medulla).
• The functional unit is the nephron; • 106 nephrons/Kidney.
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The Nephron
Renal artery
Glomerulus
Bowman’s capsule
Proximal tubule
Distal tubule
Collecting duct
Henle’s Loop
Afferent arteriole
Vasa Recta
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KIDNEY: Blood flow 1
Renalartery
Inter-lobar artery
Arcuate artery
Inter-lobular artery
1
2
3
4
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KIDNEY: Blood flow 4 Venous drainage
Renalvein
Inter-lobar vein
Arcuate vein
Inter-lobular vein
12
11
10
9
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FILTRATION BARRIER
Capillarylumen
Fenestrated endothelium Basal lamina
Podocytes with
Fenestration Basal lamina Filtration slit closed by a diaphragm
Filtrationslitsbetweenfeet
Capsular space
Capsularspace
The charged proteoglycans of the BL help control what
passes through
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Why Test Renal Function?
• To identify renal dysfunction.• To diagnose renal disease.• To monitor disease progress.• To monitor response to treatment.• To assess changes in function that may
impact on therapy (e.g.Digoxin, chemotherapy).
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Renal Functions• Production of urine
– Elimination of metabolic end products (Urea/Creatinine)
– Elimination of foreign materials (Drugs)
– Control of volume & composition of ECF
• Water and electrolyte balance
• Acid/Base status
• Endocrine Functions• Vit D, Epo, Renin
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Biochemical Tests of Renal Function• Urinalysis
– Appearance– Specific gravity and osmolality– pH– Glucose– Protein– Urinary sediments?
• Measurement of GFR– Clearance tests– Plasma creatinine
• Tubular function tests
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Determination of Clearance• Clearance = (U xV)/P
Where U is the urinary concentration of substance xV is the rate of urine formation (mL/min)P is the plasma concentration of substance x
• Units = volume/unit time (mL/min)• If clearance = GFR then substance x properties: -
– freely filtered by glomerulus– glomerulus = sole route of excretion from the body (no
tubular secretion or reabsorbtion) – Non-toxic and easily measurable
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• 1-2%/day of muscle creatine converted to creatinine• Amount produced relates to muscle mass• Freely filtered at the glomerulus• Some tubular excretion.
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Plasma Creatinine Concentration
Difficulties: -• Concentration depends on balance between input and
output.• Production determined by muscle mass which is related to
age, sex and weight.• High between subject variability but low within subject.• Concentration inversely related to GFR.
– Small changes in creatinine within and around the reference limits = large changes in GFR.
• Reference limits can be misleading
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Relationship between Serum Creatinine Concentration and Creatinine Clearance
0100200300400500600700800
0 25 50 75 100 125Creatinine Clearance (ml/min)
Seru
m C
reat
inin
e (µ
mol
/L)
ULN
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OutputKidney
PlasmaPoolContent
CreatinineInput
NormalMuscleMass
NormalKidneys
DiseasedKidneys
NormalMuscleMass
DiseasedKidneys
NormalKidneys
IncreasedMuscleMass
ReducedMuscleMass
Effect of Muscle Mass on Serum Creatinine
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Measurement of Glomerular Filtration Rate (GFR)
• GFR is essential to renal function
• Most frequently performed test of renal function.
• Measurement is based on concept of clearance: -
“The determination of the volume of plasma from which a substance is removed by glomerularfiltration during it’s passage through the kidney”
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Acute Renal Failure
Metabolic features: -• Retention of: -
– Urea & creatinine– Na & water– potassium with hyper-
kalaemia– Acid with metabolic
acidosis
Classification of Causes:• Pre-renal
– reduced perfusion
• Intrinsic Renal– vascular– inflammation– infiltration– toxicity
• Post-renal– obstruction
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Pre-renal versus intrinsic ARF
Test Result
Pre-renal Renal
Urea & Creatinine Disproportionaterise in Urea
Tend to risetogether
Protein in urine Uncommon Present ondipsticktesting
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What are the functions of the kidneys?
• Regulate body fluid osmolality and volume• Regulate electrolyte balance• Regulate acid-base balance• Excrete metabolic products and foreign
substances• Produce and excrete hormones• Gluconeogenic
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Glomerular filtrationGlomerlular
capillarymembrane
Vascular spaceVascular space Bowman’s spaceBowman’s space
Mean capillary bloodpressure = 50 mm Hg
BC pressure = 10 mm Hg
Onc. pressure = 30 mm Hg
Net hydrostatic = 10 mm Hg
∼ 200 Litersper day
GFR ≅ 110 mL/min
∼ 2,000 Litersper day
(25% of cardiac output)
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Dynamics?
• 200 liters of filtrate enter the nephrons/day– 1-2 liters of urine produced– filtrate (99+ %) is reabsorbed.
• Reabsorption– active or passive– occurs in virtually all segments of the nephron.
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What makes it into the glomerular filtrate?
• Freely filtered– H2O– Na+, K+, Cl-,
HCO3-, Ca++,
Mg+, PO4, etc.– Glucose– Urea– Creatinine– Insulin
• Less freely filtered– β2-
microglobulin– RBP– α1-
microglobulin– Albumin
• Not usually filtered– Immunoglobulins– Ferritin– Cells
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Functions of renal tubules
• Selective reabsorbtion or excretion of water and various ions to maintain constancy of the body electrolyte composition.
• Active reabsorption of filtered compounds, such as glucose and amino acids
• Acquired and inherited disorders of tubular mechanisms lead to characteristic syndromes (Fanconi, RTA)
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Reabsorption from glomerularfiltrate
% ReabsorbedWater 99.2
Sodium 99.6Potassium 92.9Chloride 99.5
Bicarbonate 99.9Glucose 100Albumin 95-99
Urea 50-60Creatinine 0 (or negative)
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Tubular Reabsorbtion and Secretion of Organic Substances
• Active– Glucose– Amino acids– Proteins (pinocytosis)– 3 secretory systems ; functionally identified: -
• organic acids (PAH, penicillin)• Strong organic bases (TEA)• (EDTA)
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JUXTAGLOMERULAR APPARATUS
Thinsegment
Distaltubule
Collectingduct
Proximal tubule
Archedcollectingtubule
~
~~
~
~~~
~~ ~
~~~
VasarectaInterstitiu
mDistaltubule
Renin-secretingJG cells
Flow & NaCl-sensing Macula densa
Afferentarteriole
Efferentarteriole
Mesangium
1
2
3
Renalcorpuscle
Renalcorpuscle
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Renalcorpuscle
Distaltubule
Renin-secretingJG cells
Flow & NaCl-sensingMacula densa
Afferentarteriole
Efferent arteriole
JUXTAGLOMERULAR APPARATUS 2
Vascular smoothmuscle cells
for single-nephron tubulo-glomerular feedback to relateglomerular flow to distal flow rate
Mesangium
High luminal flow results inVSMC Vasoconstriction
NaCl
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Renalcorpuscle
Distaltubule
Renin-secretingJG cells
Afferentarteriole
Efferent arteriole
JUXTAGLOMERULAR APPARATUS 3
Vascular smooth muscle cells
The renin-secreting JG cellsare modified arteriolar smoothmuscle cells. More can berecruited as needed.
Mesangium
NaCl
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Distaltubule
Renin-secretingJG cells
Flow & NaCl-sensingMacula densa
Afferentarteriole
Efferent arteriole
JUXTAGLOMERULAR APPARATUS 4
Vascular smoothmuscle cells
Mesangium
NaCl
Low distal NaCl causes JG-mediated renin release & subsequent effects via angiotensin and aldosterone
Renalcorpuscle
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Afferentarteriole
Efferent arteriole
JUXTAGLOMERULAR APPARATUS 5
Vascular smoothmuscle cells
Renin-secretingJG cells
NaCl
Low distal NaCl causes JG-mediatedrenin release & subsequent effectsvia angiotensin and aldosterone
Renalcorpuscle
Angiotensinogen
Angiotensin I
Angiotensin II
Aldosterone
Renin
Converting
enzyme
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Thinsegment
Distaltubule
Collectingduct
Proximaltubule
Archedcollectingtubule
~
~~
~
~~~
~~ ~
~~~
VasarectaInterstitiu
m
SOME RENAL DISEASES
FIBROSIS
TUBULAR epithelialNEPHROTOXICITY fromaminoglycosides & heavy metals
RENAL ISCHEMIAGLOMERULONEPHRITIS e.g., mesangial-cellreaction
DIABETES INSIPIDUS pituitary or nephrogenic
Renalcorpuscle
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Osmoticpressure
Volume
Hydrostatic pressure
Oncoticpressure
Vascular
ExtravascularCRRT
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Osmoticpressure
Volume
Hydrostatic pressure
Oncoticpressure
Vascular
Extravascular
Hypovolemia
CRRT
Consequencesdepend on:•duration•permeability(ies)•rate
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1) DO2 = CO x SaO2 x Hb x 1.34
2) CO = HR x SV
Danger : Oxygen delivery impairment
3) SV = function (ventricular preload)Franck Starling law
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Cardiac Preload - Franck Starling law
Ventricular stroke volume
Ventricular preload
No preloaddependence
Preloaddependence
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Relation between vascular volume and ventricular function
Ventricular stroke volume
Ventricular preload
Osmotic pressure
Volume
1
1
2
2
33
MAP = SV x HR x SVR
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Definition of Terms
• SCUF - Slow Continuous Ultrafiltration• CAVH - Continuous Arteriovenous Hemofiltration• CAVH-D - Continuous Arteriovenous Hemofiltration with
Dialysis • CVVH - Continuous Venovenous Hemofiltration• CVVH-D - Continuous Venovenous Hemofiltration with
Dialysis
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Indications for Continuous Renal Replacement Therapy
• Remove excess fluid because of fluid overload• Clinical need to administer fluid to someone who is oliguric
– Nutrition solution– Antibiotics– Vasoactive substances– Blood products– Other parenteral medications
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Basic Principles
• Blood passes down one side of a highly permeable membrane
• Water and solute pass across the membrane– Solutes up to 20,000 daltons
• Drugs & electrolytes
• Infuse replacement solution with physiologic concentrations of electrolytes
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Anatomy of a Hemofilter
blood inblood in
blood out
dialysatein
dialysateout
Outside the Fiber (effluent)Inside the Fiber (blood)
Cross Sectionhollow fiber membra
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Basic Principles
• Hemofiltration– Convection based on a pressure gradient– ‘Transmembrane pressure gradient’
• Difference between plasma oncotic pressure and hydrostatic pressure
• Dialysis– Diffusion based on a concentration gradient
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Blood InBlood In
Blood OutBlood Out
to wasteto waste (from patient)(from patient)
(to patient)to patient)
HIGH PRESSHIGH PRESSLOW PRESSLOW PRESS
ReplRepl..SolutionSolution
CVVHContinuous Veno-Venous Hemofiltration
(Convection)(Convection)
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CVVHContinuous VV Hemofiltration
• Primary therapeutic goal:– Convective solute removal– Management of intravascular volume
• Blood Flow rate = 10 - 180 ml/min • UF rate ranges 6 - 50 L/24 h (> 500 ml/h)• Requires replacement solution to drive convection• No dialysate
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ReplRepl..SolutionSolution
DialysateSolution
Blood InBlood In
Blood OutBlood Out
to wasteto waste
(from patient)(from patient)
((to patient)to patient)
HIGH PRESSHIGH PRESSLOW PRESSLOW PRESS
HIGH CONCHIGH CONCLOW CONCLOW CONC
CVVHDFContinuous Veno-Venous Hemodiafiltration
(Diffusion)(Diffusion)(Convection)(Convection)
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CVVHDFContinuous VV Hemodiafiltration• Primary therapeutic goal:
– Solute removal by diffusion and convection– Management of intravascular volume
• Blood Flow rate = 10 - 180ml/min • Combines CVVH and CVVHD therapies• UF rate ranges 12 - 24 L/24h (> 500 ml/h)• Dialysate Flow rate = 15 - 45 ml/min (~1 - 3 L/h)• Uses both dialysate (1 L/h) and replacement fluid (500
ml/h)
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introduction• Continuous
veno-venous hemofiltration(CVVH) allows removal of solutes and modification of the volume and composition of the extracellularfluid to occur evenly over time.
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hemofiltration
•A small filter that is highly permeable to water and small solutes, butimpermeable to plasma proteins and the formed elements of the blood, is placed in an extracorporeal circuit.
•As the blood perfuses the 'hemofilter' an ultrafiltrate of plasma is removed in a manner analogous to glomerularfiltration.
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CVVH• 1. near-complete control of the rate of
fluid removal (i.e. the ultrafiltrationrate)
• 2. precision and stability
• 3. electrolytes or any formed element of the circulation, including platelets or red or white blood cells, be removed or added independently of changes in the volume of total body water.
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ultrafiltration• Filtration across an ultrafiltration membrane is
convective, similar to that found in the glomerulus of the kidney.
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convection• convection• a solute molecule is swept through a
membrane by a moving stream of ultrafiltrate, a process that is also called 'solvent drag.'
• hemofiltration• during hemofiltration no dialysate is used,
and diffusive transport cannot occur. Solute transfer is entirely dependent on convective transport, making hemofiltration relatively inefficient at solute removal.
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hemodialysis
• Hemodialysis allows the removal of water and solutes by diffusion across a concentration gradient.
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diffusion• diffusion• solute molecules are transferred across
the membrane in the direction of the lower solute concentration at a rate inversely proportional to molecular weight.
• hemodialysis• during hemodialysis, solute movement
across the dialysis membrane from blood to dialysate is primarily the result of diffusive transport.
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biocompatibility• Various synthetic materials are used in hemofiltrationmembranes: – polysulfone– polyacrylonitrile– polyamide
• all of which are extremelybiocompatible. Consequently, complement activation and leukopenia, both of which are common in hemodialysis, occur infrequently during hemofiltration.
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hemofiltration membrane
Hemodialysis membranes contain long, tortuous inter-connecting channels that result in high resistance to fluid flow.
The hemofiltrationmembrane consists of relatively straight channels of ever-increasing diameter that offer little resistance to fluid flow.
phosphatebicarbonateinterleukin-1interleukin-6endotoxinvancomycinheparinpesticidesammonia
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hemofiltration membrane
Hemofilters allow easy transfer of solutes of less than 100 daltons (e.g. urea, creatinine, uric acid, sodium, potassium, ionized calcium and almost all drugs not bound to plasma proteins). All CVVH hemofilters are impermeable to albumin and other solutes of greater than 50,000 daltons.
phosphatebicarbonate
ionized Ca++interleukin-6
endotoxinvancomycin
heparinpesticidesammonia
albumin protein-bound
medications platelets
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sluggishness
• A filtration rate of more than 25 - 30% greatly increases blood viscosity within the circuit, risking clot and malfunction.
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pre-dilution
• Sludging problems are reduced, but the efficiency of ultrafiltration is compromised, as the ultrafiltrate now contains a portion of the replacement fluid.
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experimental: high flow
• High-volume CVVH might improve hemodynamics, increase organ blood flow, and decreased blood lactate and nitrite/nitrate concentrations.