AORN A.CARDARELLI NAPOLI dr.E.Di Florio III Water and electrolyte balance • Acid/Base status...

AORN A.CARDARELLI NAPOLIdr.E.Di Florio III SAR

Renal Anatomy

Cortex

Medulla

Pelvisof theureter

To the bladder

Capsule

Ureter

Renal Artery& Veins

Medulary Pyramid

11cm

6 cm3cm

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.

The Nephron

Renal artery

Glomerulus

Bowman’s capsule

Proximal tubule

Distal tubule

Collecting duct

Henle’s Loop

Afferent arteriole

Vasa Recta

KIDNEY: Blood flow 1

Renalartery

Inter-lobar artery

Arcuate artery

Inter-lobular artery

1

2

3

4

KIDNEY: Blood flow 4 Venous drainage

Renalvein

Inter-lobar vein

Arcuate vein

Inter-lobular vein

12

11

10

9

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

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).

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

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

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

• 1-2%/day of muscle creatine converted to creatinine• Amount produced relates to muscle mass• Freely filtered at the glomerulus• Some tubular excretion.

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

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

OutputKidney

PlasmaPoolContent

CreatinineInput

NormalMuscleMass

NormalKidneys

DiseasedKidneys

NormalMuscleMass

DiseasedKidneys

NormalKidneys

IncreasedMuscleMass

ReducedMuscleMass

Effect of Muscle Mass on Serum Creatinine

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”

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

Pre-renal versus intrinsic ARF

Test Result

Pre-renal Renal

Urea & Creatinine Disproportionaterise in Urea

Tend to risetogether

Protein in urine Uncommon Present ondipsticktesting

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

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)

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.

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

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)

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)

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)

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

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

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

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

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

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

Osmoticpressure

Volume

Hydrostatic pressure

Oncoticpressure

Vascular

ExtravascularCRRT

Osmoticpressure

Volume

Hydrostatic pressure

Oncoticpressure

Vascular

Extravascular

Hypovolemia

CRRT

Consequencesdepend on:•duration•permeability(ies)•rate

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

Cardiac Preload - Franck Starling law

Ventricular stroke volume

Ventricular preload

No preloaddependence

Preloaddependence

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

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

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

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

Anatomy of a Hemofilter

blood inblood in

blood out

dialysatein

dialysateout

Outside the Fiber (effluent)Inside the Fiber (blood)

Cross Sectionhollow fiber membra

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

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)

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

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)

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)

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.

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.

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.

ultrafiltration• Filtration across an ultrafiltration membrane is

convective, similar to that found in the glomerulus of the kidney.

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.

hemodialysis

• Hemodialysis allows the removal of water and solutes by diffusion across a concentration gradient.

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.

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.

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

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

sluggishness

• A filtration rate of more than 25 - 30% greatly increases blood viscosity within the circuit, risking clot and malfunction.

pre-dilution

• Sludging problems are reduced, but the efficiency of ultrafiltration is compromised, as the ultrafiltrate now contains a portion of the replacement fluid.

experimental: high flow

• High-volume CVVH might improve hemodynamics, increase organ blood flow, and decreased blood lactate and nitrite/nitrate concentrations.