CHRONIC RENAL FAILURE Valerie Kolmer RN BSN BC MSN 621 Alverno College
Objectives Upon completion of this tutorial the learner will: • Have an increased understanding of the pathophysiology of Chronic Renal Failure • Recognize the signs and symptoms of Chronic Renal Failure • Identify the disease progression and treatment interventions
Chronic Renal FailureTutorial Guide • Return to the main menu at any time by pushing the button. • Hyperlinks to outside sources, for in-depth information, are available on various slides. Just push on the button. Click back button to return. • Easy navigation forward or backward using the or buttons. • Within text - highlighted words link to definitions - then return with button Main Menu Link
Chronic Renal FailureMain Menu • Tutorial Guide • Definitions • Renal Physiology Review • Pathophysiology • Causes • Signs & Symptoms • Hyperlipidemia in CRF • Inflammation • Pharmacology • Case Study/Quiz • References
Definitions • CRF= Chronic Renal Failure – permanent loss of nephrons and renal function • Erythropoietin = Hormone produced by kidneys and regulates production of RBC’s • Filtrate= Liquid entering the nephron • Filtration= Movement of liquid through a membrane (like a sieve), allows only small molecules & liquids to pass through. Movement is from higher to lower pressure • GFR= Glomerular Filtration Rate – amount of filtrate produced each minute • Glomerulus= Filtration system of the nephron, composed of capillaries surrounded by a thin double-walled capsule, called Bowman’s Capsule
Definitions • Lysosome = Membrane bound organelles, within the cell, containing hydrolytic enzymes - involved in intra & extracellular digestion • Mesangial Cells = Supporting cells of glomeruli- produce intracellular substances • Nephron = Functional unit of the kidney • Reabsorption = Movement of substances from the filtrate back into the blood • Renal Corpuscle = Glomerulus and surrounding epithelial capsule. • Secretion = Active transport of solutes into the nephron
Renal Physiology Review The Kidneys: • Control the fluid/electrolyte balance for the body • Remove metabolic wastes from the blood & excrete them to the outside • Regulate red-blood cell production • Regulate blood-pressure • Important in calcium ion absorption • Control volume, composition and pH of the blood Link: Renal Physiology
Renal Hormone Regulation Synthesis and activation of hormones by the kidney include: • Active form of Vitamin D • Erythropoietin Renal blood flow regulated by: Renin-angiotensin aldosterone system (RAAS)
Fluid and Electrolyte ControlMechanisms • RAAS – Renin-Angiotensin Aldosterone System • Aldosterone • ADH – Anti-Diuretic Hormone
How the RAAS Pathway Works Valerie Kolmer 2006
Aldosterone • Increases rate of sodium ion absorption • Chloride moves along with sodium because of + charge of sodium • Increases rate of potassium & hydrogen ion secretion Result: Fluid and sodium retention increases blood-pressure
Quick Quiz Pick the correct pathway of the RAAS • Renin – Angiotensin II – ACE – ADH – Aldosterone • Renin – Angiotensin I – Aldosterone – ADH –ACE • Renin – Angiotensin I – ACE – Angiotensin II – Aldosterone
Renin – Angiotensin II- ACE- ADH – Aldosterone That is not correct Please try again Answer 1.
Answer 2. Renin – Angiotensin I – Aldosterone – ADH - ACE That is not correct Please Try Again
Answer 3. Renin – Angiotensin I – ACE – Angiotensin II – Aldosterone You are RIGHT!
Renal Structure • Each kidney has a renal pelvis (divided into major & minor calyces),renal cortex (the outer portion) & renal medulla (lies under the cortex) • Within the renal medulla there are many renal pyramids that consist of multiple nephrons (the functional units of the kidney) • The renal pelvis collects the urine & passes it to the ureter
Nephron(b) Renal Pyramid with Nephrons(c) Section of Kidney Shier,D., Butler, J., Lewis, R (1999). Hole’s human anatomy and physiology.(8th ed.). The McGraw-Hill Co, Inc. Used with permission: The McGraw-Hill Companies
The Nephron Each kidney contains approximately a million nephron’s Filtered fluid from the blood enters: • The renal corpuscle (consisting of the glomerulus) • Proximal convoluted tubule • Loop of Henle (descending & ascending limb) • Distal convoluted tubule Shier, D., Butler, J., Lewis, R. (1999). Hole’s human anatomy & physiology(8th ed.). The McGraw-Hill Co., Inc.
Nephron & Blood Supply Shier,D., Butler, J., Lewis, R (1999). Hole’s human anatomy and physiology.(8th ed.). The McGraw-Hill Co, Inc. Used with permission: The McGraw-Hill Companies
Urine Formation • Efferent arteriole constriction causes the blood in the glomerulus to be under high pressure. • Filtrate: the water and other small molecules that move into the glomerular capsule. Approximately 45 gallons of filtrate are produced each day. Most of the water and molecules are reabsorbed along the tubules as the filtrate passes through. Shier, D., Butler, J., Lewis, R. (1999). Hole’s human anatomy & physiology(8th ed.). The McGraw-Hill Co., Inc.
What is Glomerular Filtration Rate (GFR)? • The GFR is the measurement of the kidneys ability to filter waste products • It shows the volume of H2O and solutes filtered out of blood plasma through the glomeruli over a period of time • Common measurement is the Cockcroft-Gault equation that estimates creatinine clearance Link: GFR Info
Urine Formation Modified from: Shier, D., Butler, J., Lewis, R. (1999). Hole’s human anatomy & physiology(8th ed.). The McGraw-Hill Co.,Inc.
Nephron Component Functions Filtration of H2O and dissolved substances from the plasma Reabsorption of Na ions, Water, Secretion of hydrogen ions and K+ ions Reabsorption of glucose, calcium, K+, Na, proteins and H2O Reabsorption of Na, K+ & Chloride ions Shier, D., Butler, J., Lewis, R. (1999). Hole’s human anatomy and physiology (8th ed.). The McGraw-Hill Co, Inc. Used with permission: The McGraw-Hill Companies
Pathophysiology of CRF What is Chronic Renal Failure? It is progressive tissue destruction with permanent loss of nephrons and renal function.
Risk Factors • Age > 60 years • Race or ethnic background African-American Hispanic American Indian Asian • History of exposure to chemicals/toxins Cigarette smoke Heavy metals • Family history of chronic kidney disease
Chronic vs. Acute Renal Failure • Acute Renal Failure (ARF): • Abrupt onset • Potentially reversible • Chronic Renal Failure (CRF): • Progresses over at least 3 months • Permanent- non-reversible damage to nephrons
Pathophysiology of CRF Progressive destruction of nephrons leads to: • Decreased glomerular filtration, tubular reabsorption & renal hormone regulation • Remaining functional nephrons compensate • Functional and structural changes occur • Inflammatory response triggered • Healthy glomeruli so overburdened they become stiff, sclerotic and necrotic Lippincott Williams & Wilkins (2005). Pathophysiology A 2-1 reference for nurses (1st ed.) Ambler, Pa.:Lippincott Williams & Wilkins
Functional Changes of CRF The Kidneys are unable to: • Regulate fluids and electrolytes • Balance fluid volume and renin-angiotensin system • Control blood pressure • Eliminate nitrogen and other wastes • Synthesize erythropoietin • Regulate serum phosphate and calcium levels
Structural Changes of CRF • Epithelial damage • Glomerular and parietal basement membrane damage • Vessel wall thickening • Vessel lumen narrowing leading to stenosis of arteries and capillaries • Sclerosis of membranes, glomeruli and tubules • Reduced glomerular filtration rate • Nephron destruction Healthy Glomerulus Damaged Glomerulus Valerie Kolmer 2006
4 Stages of CRF • Reduced Renal Reserve (Silent): no symptoms evident- GFR up to 50ml/min • Renal Insufficiency: ½ function of both kidneys lost- GFR 25-50 ml/min • Renal Failure: GFR 5-25 ml/min • End Stage Renal Disease: GFR less than 5 ml/min Link: GFR Info
Quick Quiz Chronic Renal Failure is reversible. True False
Sorry! That is not correct. The answer is false. Nephron damage is permanent & progressive in CRF Please continue.
Causes of CRF • Diabetic Nephropathy • Hypertension • Vascular Disease • Polycystic Kidney Disease/Genetics • Chronic Inflammation • Obstruction • Glomerular Disorders/ Glomerulonephritis
SIGNS & SYMPTOMSLab Value Cues Anemia’s - d/t decreased erythropoietin secretion & uremic toxin damage to RBC’s Azotemia – (elevated nitrogen) d/t retention of nitrogenous wastes Creatinine – a component of muscle & it’s non-protein waste product. Normally filtered in the glomerulus & lost in the urine. Glomerular damage increases reabsorption into the blood. Serum creatinine 3 x normal shows a 75% loss of renal function. http://office.microsoft.com/en-us/tou.aspx
Hypocalcemia – impaired regulation of Vitamin D leads to decreased absorption & low calcium levels. High phosphorus levels also cause low serum calcium levels. Hyperkalemia – impaired excretion of potassium by the kidneys leads to elevated potassium levels. Hyperlipidemia – decreased serum albumin leads to increased synthesis of LDL’s & cholesterol by the liver, contributing to elevated lipid levels Proteinuria – increased protein filtration d/t glomeruli damage SIGNS & SYMPTOMSLab Value Cues http://office.microsoft.com/en-us/tou.aspx
Dry mouth, fatigue, nausea – d/t hyponatremia & uremia Hypertension – d/t sodium & water retention Hypervolemia – d/t sodium & water retention Gray/yellow skin – d/t accumulated urine pigments Cardiac irritability – d/t hyperkalemia Muscle cramps – d/t hypocalcemia Bone & muscle pain – d/t hypocalcemia / hyperphosphatemia Restless leg syndrome – d/t toxins’ effects on the nervous system SIGNS & SYMPTOMSVisual / Verbal Cues http://office.microsoft.com/en-us/tou.aspx
Genetics of Kidney Disease Genetic diseases that cause CRF: • Polycystic Kidney Disease (PKD) • Nephropathic Cystinosis (Fanconi’s Syndrome) • Alport Syndrome Sanford, R. (2004). Autosomal dominant polycystic kidney disease. Retrieved February 8, 2006, http://www.cgkp.org.uk/topics/cam-genetics/sanford.htm
Polycystic Kidney Disease • Most Common Genetic Disorder • Numerous fluid-filled cysts in kidneys and renal tubules • Normal renal tissue replaced by cysts • Decreased function leads to end-stage renal disease Polycystic jpg 58_001.connection.ww.com/…/Ch58/jpg/58_001.jpg
Two Major Forms PKD • Autosomal Dominant PKD • Autosomal Recessive PKD Only treatment for both = dialysis and kidney transplantation Used with permission: Lippincott Williams & Wilkins
Autosomal Dominant PKD • 90% of the cases of PKD are this form • 4th leading cause of renal failure age 40-60 • Undetected for years until symptoms develop • Occurs equally males and females, mainly Caucasians • One parent with ADPKD gene = 50% chance children will inherit disease • Gene mutation on chromosome 16 or 4
Autosomal Recessive PKD • Rare form – occurs in 1 in 4 babies (of parents with mutation) • Worst cases die within hours of birth • Both parents with gene mutation • Mutation on chromosome 6 • 25% chance children will inherit disease
Metabolic Impact • Hyperlipidemia common in CRF- especially in Nephrotic Syndrome • Excessive lipids accelerate progression of renal disease • Cholesterol increases glomerular injury
Contributing Mechanisms Two known paths of hyperlipidemia progression in CRF: • Hyperlipidemia activates LDL receptors in mesangial cells • Increased synthesis of lipoproteins in the liver related to increased albumin production
Mesangial Cell Contribution Valerie Kolmer 2006
Albumin Contribution Normal glomeruli structure limits proteins from filtering through the urine • Progression of glomeruli injury leads to increased capillary filtration of albumin • The liver compensates and increases albumin production - to replace albumin lost in urine • This leads to increased synthesis of lipoproteins by the liver secondary to the compensatory increase in albumin production. • Results in increased LDL levels – predisposing to atherosclerosis • Atherosclerosis further increases glomeruli injury
Inflammation • Inflammatory response can be triggered by: tissue injury, infections, toxins, immune responses and/or Angiotensin II • Can be acute or chronic • Can affect the renal pelvis and interstitial tissue as in pyelonephritis • Can affect the glomeruli as in glomerulonephritis
Inflammation- (Cont.) Renal Failure- prolongs inflammatory reactions • Adverse effects of chronic inflammation= Decreased appetite Muscle and fat wasting Endothelial damage Atherosclerosis Hypoalbuminemia Increased cardiovascular disease risk Legg, V.(2005). Complications of chronic kidney disease. AJN,105(6),40-50