AORN A.CARDARELLI NAPOLI dr.e.di Florio III SAR

Transcription

1 AORN A.CARDARELLI NAPOLI dr.e.di Florio III SAR

2 Renal Anatomy Renal Artery & Veins 6 cm 3cm Cortex 11cm Pelvis of the ureter Capsule Ureter To the bladder Medulla Medulary Pyramid

3 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; 10 6 nephrons/kidney.

4 The Nephron Afferent arteriole Glomerulus Bowman s capsule Proximal tubule Distal tubule Collecting duct Renal artery Vasa Recta Henle s Loop

5 KIDNEY: Blood flow 1 Inter-lobar artery 2 Arcuate artery 3 Renal artery 1 Inter-lobular artery 4

6 KIDNEY: Blood flow 4 Venous drainage Inter-lobar vein 11 Renal vein 12 Arcuate vein 10 Inter-lobular vein 9

7 FILTRATION BARRIER Fenestrated endothelium Basal lamina The charged proteoglycans of the BL help control what passes through Capsular space Capillary lumen Podocytes with Filtration slits between feet Capsular space Fenestration Basal lamina Filtration slit closed by a diaphragm

8 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).

9 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

10 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

11 Determination of Clearance Clearance = (U xv)/p Where U is the urinary concentration of substance x V 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

12 1-2%/day of muscle creatine converted to creatinine Amount produced relates to muscle mass Freely filtered at the glomerulus Some tubular excretion.

13 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

14 Relationship between Serum Creatinine Concentration and Creatinine Clearance Serum Creatinine (µmol/l) Creatinine Clearance (ml/min) ULN

15 Effect of Muscle Mass on Serum Creatinine Creatinine Input Normal Muscle Mass Normal Muscle Mass Increased Muscle Mass Reduced Muscle Mass Plasma Pool Content Output Kidney Normal Kidneys Diseased Kidneys Normal Kidneys Diseased Kidneys

16 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 glomerular filtration during it s passage through the kidney

17 Acute Renal Failure Metabolic features: - Retention of: - Urea & creatinine Na& water potassium with hyperkalaemia Acid with metabolic acidosis Classification of Causes: Pre-renal reduced perfusion Intrinsic Renal vascular inflammation infiltration toxicity Post-renal obstruction

18 Pre-renal versus intrinsic ARF Test Result Pre-renal Renal Urea & Creatinine Disproportionate rise in Urea Tend to rise together Protein in urine Uncommon Present on dipstick testing

19 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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22 Glomerular filtration Vascular space 2,000 Liters per day (25% of cardiac output) Glomerlular capillary membrane Mean capillary blood pressure = 50 mm Hg BC pressure = 10 mm Hg Onc. pressure = 30 mm Hg Bowman s space 200 Liters per day Net hydrostatic = 10 mm Hg GFR 110 ml/min

23 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.

24 What makes it into the glomerular filtrate? Freely filtered H 2 O Na +, K +, Cl -, HCO 3-, Ca ++, Mg +, PO 4, etc. Glucose Urea Creatinine Insulin Less freely filtered β 2 - microglobulin RBP α 1 - microglobulin Albumin Not usually filtered Immunoglobulins Ferritin Cells

25 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)

26 Reabsorption from glomerular filtrate % Reabsorbed Water 99.2 Sodium 99.6 Potassium 92.9 Chloride 99.5 Bicarbonate 99.9 Glucose 100 Albumin Urea Creatinine 0 (or negative)

27 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)

28 JUXTAGLOMERULAR APPARATUS Renal corpuscle Reninsecreting JG cells 3 2 Mesangium Renal corpuscle Afferent arteriole Proxima l tubule Interstitiu m Distal tubule ~ Distal tubule ~ ~ ~ ~ ~ ~ Thin segment Collecting duct ~ ~ ~ ~ Arched collecting tubule ~ Vasa recta Flow & NaCl-sensing Macula densa Efferent arteriole 1 ~

29 JUXTAGLOMERULAR APPARATUS 2 Reninsecreting JG cells Afferent arteriole Vascular smooth muscle cells High luminal flow results in VSMC Vasoconstriction NaCl Distal tubule for single-nephron tubuloglomerular feedback to relate glomerular flow to distal flow rate Mesangium Renal corpuscle Flow & NaCl-sensing Macula densa Efferent arteriole

30 JUXTAGLOMERULAR APPARATUS 3 Efferent arteriole Reninsecreting JG cells Afferent arteriole The renin-secreting JG cells are modified arteriolar smooth muscle cells. More can be recruited as needed. Vascular smooth muscle cells Mesangium Renal corpuscle NaCl Distal tubule

31 JUXTAGLOMERULAR APPARATUS 4 Reninsecreting JG cells Afferent arteriole Vascular smooth muscle cells Distal tubule Low distal NaCl causes JGmediated renin release & subsequent effects via angiotensin and aldosterone NaCl Mesangium Renal corpuscle Efferent arteriole Flow & NaCl-sensing Macula densa

32 JUXTAGLOMERULAR APPARATUS 5 Vascular smooth muscle cells Reninsecreting JG cells Afferent arteriole Renin Low distal NaCl causes JG-mediated renin release & subsequent effects via angiotensin and aldosterone Angiotensinogen Angiotensin I Converting enzyme NaCl Angiotensin II Renal corpuscle Efferent arteriole Aldosterone

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34 SOME RENAL DISEASES GLOMERULONEPHRITIS e.g., mesangial-cell reaction TUBULAR epithelial NEPHROTOXICITY from aminoglycosides & heavy metals Proximal tubule Interstitiu m FIBROSIS RENAL ISCHEMIA Renal corpuscle ~ Distal tubule ~ ~ ~ ~ ~ ~ Thin segment Collecting duct ~ ~ ~ ~ Arched collecting tubule ~ Vasa recta ~ DIABETES INSIPIDUS pituitary or nephrogenic

35 Osmotic pressure Vascular Extravascular CRRT Hydrostatic pressure Oncotic pressure Volume

36 Osmotic pressure Vascular Hypovolemia CRRT Extravascular Oncotic pressure Hydrostatic pressure Consequences depend on: duration permeability(ies) rate Volume

37 Danger : Oxygen delivery impairment 1) DO2 = CO x SaO2 x Hb x ) CO = HR x SV 3) SV = function (ventricular preload) Franck Starling law

38 Cardiac Preload - Franck Starling law Ventricular stroke volume No preload dependence Preload dependence Ventricular preload

39 Relation between vascular volume and ventricular function Osmotic pressure Ventricular stroke volume Volume 3 Ventricular preload MAP = SV x HR x SVR

40 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

41 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

42 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

43 Anatomy of a Hemofilter blood in dialysate out Cross Section hollow fiber membra dialysate in blood out Outside the Fiber (effluent) Inside the Fiber (blood)

44 Basic Principles Hemofiltration Convection based on a pressure gradient Transmembrane pressure gradient Dialysis Difference between plasma oncotic pressure and hydrostatic pressure Diffusion based on a concentration gradient

45 CVVH Continuous Veno-Venous Hemofiltration to waste Blood In (from patient) Repl. Solution Blood Out (to patient) LOW PRESS HIGH PRESS (Convection)

46 CVVH Continuous VV Hemofiltration Primary therapeutic goal: Convective solute removal Management of intravascular volume Blood Flow rate = ml/min UF rate ranges 6-50 L/24 h (> 500 ml/h) Requires replacement solution to drive convection No dialysate

47 CVVHDF Continuous Veno-Venous Hemodiafiltration Dialysate Solution to waste Blood In (from patient) Repl. Solution Blood Out (to patient) LOW PRESS LOW CONC HIGH PRESS HIGH CONC (Convection) (Diffusion)

48 CVVHDF Continuous VV Hemodiafiltration Primary therapeutic goal: Solute removal by diffusion and convection Management of intravascular volume Blood Flow rate = ml/min Combines CVVH and CVVHD therapies UF rate ranges L/24h (> 500 ml/h) Dialysate Flow rate = ml/min (~1-3 L/h) Uses both dialysate (1 L/h) and replacement fluid (500 ml/h)

49 Continuous veno-venous hemofiltration (CVVH) allows removal of solutes and modification of the volume and composition of the extracellular fluid to occur evenly over time. introduction

50 hemofiltration A small filter that is highly permeable to water and small solutes, but impermeable 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 glomerular filtration.

51 CVVH 1. near-complete control of the rate of fluid removal (i.e. the ultrafiltration rate) 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.

52 ultrafiltration Filtration across an ultrafiltration membrane is convective, similar to that found in the glomerulus of the kidney.

53 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.

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

55 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.

56 biocompatibility Various synthetic materials are used in hemofiltration membranes: polysulfone polyacrylonitrile polyamide all of which are extremely biocompatible. Consequently, complement activation and leukopenia, both of which are common in hemodialysis, occur infrequently during hemofiltration.

57 hemofiltration membrane Hemodialysis membranes contain long, tortuous interconnecting channels that result in high resistance to fluid flow. The hemofiltration membrane consists of relatively straight channels of ever-increasing diameter that offer little resistance to fluid flow. phosphate bicarbonate interleukin-1 interleukin-6 endotoxin vancomycin heparin pesticides ammonia

58 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. phosphate bicarbonate ionized Ca++ interleukin-6 endotoxin vancomycin heparin pesticides ammonia albumin protein-bound medications platelets

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

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

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