11. Renal Failure lecture notes.pdf

Siti Noor Adnalizawati bt Adnan, PhD Faculty of Dentistry Universiti Sains Islam Malaysia  Learning Objectives  Classify renal failure into acute and chronic and give definition of each category.  Explain and classify the causes of acute renal failure into pre r...

Siti Noor Adnalizawati bt Adnan, PhD Faculty of Dentistry Universiti Sains Islam Malaysia  Learning Objectives  Classify renal failure into acute and chronic and give definition of each category.  Explain and classify the causes of acute renal failure into pre renal, intrarenal and post renal.  Discuss the causes of chronic renal failure.  Describe the biochemical changes in acute and chronic renal failure.  List and interpret the relevant biochemical tests in determining renal function. Recall: Renal system - The kidneys, ureters, bladder and urethra Kidney  Nephrons  Functional subunit of kidney  1-2 million nephrons/kidney  Composed of a renal corpuscle and a tubule system  Kidneys receive 20% of cardiac output  125mL filtrate produced in 1 min  124 mL filtrate is reabsorbed  1500 mL of urine is produced in 24 hours  Renal blood flow  Aorta  Renal artery  interlobar arteries  interlobular arteries  afferent arterioles  glomerulus  efferent arterioles  In the cortex  peritubular capillaries  In the juxtamedullary region vasa recta  Back to the heart through the interlobular  intralobar  renal veins Nephron and the processes of urine formation. (Source: Pearson Education/PH College)  Juxtaglomerular apparatus (JGA) Point of contact between distal convoluted tubule & afferent arterioles  Juxtaglomerular cells Regulating blood pressure via renin-  Macula densa angiotensin-aldosterone mechanism  Extraglomerular mesangial cells  Endocrine Function  Renin–angiotensin–aldosterone system  Role in blood pressure & sodium reabsorption (BP Control)  Multisystem effect  Renin Release 10  Endocrine Function  Erythropoietin  Role in RBC production  If a patient has chronic renal failure, what condition will occur? 11  Function  Vitamin D & calcium regulation  Activate Vitamin D (Calcitriol)  Necessary to absorb Calcium in the GI tract. If a patient has renal failure, what will happen to the patient’s serum calcium level?  Function  Acid–base balance  Regulates acid-base balance through  HCO3 and H + Renal Failure  Renal failure  Significantloss of both renal function to the point where less than 10-20% of normal GFR remains  Both kidneys fail to adequately filter waste products from the blood Main forms of renal failure Acute Renal Failure  Rapid & frequently reversible deterioration of renal function.  over days to weeks Causes of ARF  Causes  Pre-renal (impaired or reduced blood flow to the kidney) - Absolute decrease in ECF volume – GI losses (vomiting, diarrhea), hemorrhage and burns - Decreased renal blood flow – Heart failure, renal artery stenosis - Altered intrarenal hemodynamics – Sepsis, drugs-induced (NSAIDs/COX-2 inhibitors, ACE inhibitors); hepatorenal syndrome  Causes  Renal (acute damage to renal structures) - Acute glomerulonephritis, pyelonephritis - Acute tubular necrosis (ATN) - ischemia of kidney or damage of kidney structure from exposure to toxins, solvents, drugs & heavy metals - ATN is the most common cause of ARF  Causes  Renal (acute damage to renal structures) - Polycystic kidney disease - Acute interstitial nephritis  Causes  Post-renal (obstructed urine flow) - Renal/urethral/bladder stone, tumours, benign prostatic hyperplasia (BPH) - Tubular obstruction – crystals (calcium oxalate), proteins (myeloma cast) Urine Output in Acute Renal failure  Oliguria  daily urine output < 400 mL  In ARF, associated with a mortality rate of 75% (versus 25% mortality rate in non-oliguric patients - > 400 mL / 24 hrs) Most deaths are associated with the underlying disease process & infectious complications  Anuria  No urine production or  100mL/ 24 hrs  Probably time for dialysis  ARF Characteristics  Azotemia  accumulation of nitrogenous waste (urea, creatinine etc) & other solutes in blood  blood urea nitrogen (BUN) & creatinine levels  Not yet severe as to produce symptoms. which progresses over several hours or days  with or without oliguria  Phases of acute renal failure 1) Oliguric phase - kidneys are damaged seriously- urine production ability of kidneys declines - Urine output 400 ml (even 2500 ml) - last for 1~3 weeks - glomerular filtration rate  Phases of acute renal failure 3) Recovery phase - The glomerular filtration rate recovers - Several months to 1 year - Urea, nitrogen and creatinine level normalizes or May remain insufficient and become chronic  Clinical features  Oliguria/anuria, occasionally urine output remains normal.  Oedema (Fluid retention-swelling in the legs, ankles or feet)  Hypertension  General uraemic symptoms - Shortness of breath - Pale skin - Poor appetite - Nausea - Fatigue - Confusion - Weakness - Irregular heartbeat - Chest pain or pressure - Seizures or coma in severe cases.  Diagnosis  History & physical examination  Routine laboratory tests  Serum electrolytes - BUN, Creatinine, K+, PO4, Ca  Urine analysis - Specific gravity, Protein, Creatinine clearance (GFR)  Ultrasound of the kidney - Structural anomalies – polycystic, obstruction, etc.  CT scan/MRI  Kidney biopsy  ARF: Biochemical changes Biochemical test Biochemical changes BUSE (Blood Urea, Blood urea: increased Serum Electrolytes) Hyperkalemia, hyponatremia Serum creatinine, Increased serum creatinine; phosphate, calcium Hyperphosphatemia, Hypocalcemia FBC (Full Blood Low Hemoglobin  anemia; Count) Normochromic normocytic anemia ABG (Arterial Blood Metabolic acidosis Gas)  Treatment/ Management  Prevention of acute renal failure - support of blood pressure and blood volume  Correction of fluid and electrolyte imbalance - Hyponatremia – fluid restriction first - Potassium - Calcium/ Bicarb/ Glucose/ Insulin/ Kayexalate  Diet control - Low protein, high carbohydrate to minimize the formation of nitrogenous waste - Low K and Phos - Decreased fluid intake Chronic Renal Failure  Chronic Renal Failure  End result of slow progressive kidney damage and loss of function occurring over 3 months to years  Irreversible  Lead to End Stage Renal Disease  Causes  ARF  Hypertension  Diabetes  Kidney disease Chronic renal failure: Causes  Diabetic nephropathy  Chronic loss of kidney function occurring in diabetes mellitus pts  Diabetes hyperglycemia  ROS  Proinflammatory cytokines & oxidative stress DN  Changes within the glomerulus:  Thickening of the basement membrane,  Podocytopathy   no. of mesangial cells, and  increase in mesangial matrix invades the glomerular capillaries expand & consume the entire glomerulus, shutting off filtration.  Glomerular diseases  Most primary glomerular diseases are immunologically mediated  The antigenic stimulus may be:  part of the glomerulus itself or  commonly - formed elsewhere in the circulation  Ag include infective agents, drugs, tumours and self- antigens such as the nucleus in SLE  Secondary glomerular damage is associated with systemic diseases such as diabetes, vasculitis including that complicating infective endocarditis, autoimmune diseases, hypertension & amyloidosis  Pts may present clinically with hematuria, proteinuria, hypertension and nephrotic syndrome.  Clinical features of CRF  Prolonged symptoms & signs of uremia  Uremia: (having urea in the blood) biochemical abnormality AND metabolic and endocrine alterations resulting from renal damage. Pathological manifestations of severe azotemia  Uremic syndrome:  Terminal clinical manifestation of renal failure  Symptoms  Anemia, hyperphosphatemia are complications of renal failure  Malaise  Dry skin  Poor appetite  Vomiting  Bone pain  Metallic taste in mouth  Detectable abdominal mass Stages Manifestations of Chronic Uremia  Treatment  Careful management of fluids and electrolytes  Diuretics  Dietary management (restriction of protein intake)  Recombinant erythropoetin to treat anemia  Renal dialysis  Renal transplantation Chronic renal failure: Laboratory  Urine analysis  Marked proteinuria + red blood cell, white blood cell and granular cast: Proliferative GN  Predominant pyuria: analgesic abuse nephropathy, renal TB, polycystic kidney.  Full blood picture  Normochromic normocytic anaemia  Blood urea serum electrolytes (BUSE)  Raised serum urea  Hyperkalemia/ hyponatremia Chronic renal failure: Laboratory  Arterial blood gas (ABG):  Metabolic acidosis  Other blood investigations:  Serum creatinine: Elevated  Hyperphosphatemia  Hypocalcemia  Evaluation of Renal Failure  Is it acute or chronic? - History and physical examination is important as laboratory values does not discriminate between both - Oliguria supports a diagnosis of acute renal failure  Clues to chronic disease - Pre-existing DM,HPT, age, vascular disease - Uremic symptoms- fatigue, nausea, anorexia, pruritus, altered taste sensation, hiccups - Small echogenic kidneys on ultrasound - Previous records  Lab investigations  Assessment of GFR  Best indicator of kidney function  Based on clearance concept –rate of urinary excretion of a substance to the plasma concentration Clearance = (U x V) / Px U = urine concentration of substance V = 24 hr urine volume Px= Plasma concentration of substance Creatinine clearance  Most widely used marker - Endogenous substance - Fairly constant rate of production by muscle - Freely filtered- not bound to protein - Not reabsorbed by renal tubule  Drawbacks - Partially secreted by proximal tubule - In severe muscle wasting or meat ingestion  Conclusion Take home message:  Evaluation of acute vs chronic renal failure is important  Treatment relies on cause of renal failure  Biochemical changes in renal failure are caused by retention of metabolites or due to disturbances in renal function