Pre-reading - Renal system.pdf

Topic : Renal System Disorders Guest lecturer Liu Peiyun MBBS, MRCP (UK), MMED (S'pore), FAMS Dr Liu is a Consultant in the Department of Renal Medicine, SGH. She is a general nephrologist trained in various a...

Topic : Renal System Disorders Guest lecturer Liu Peiyun MBBS, MRCP (UK), MMED (S'pore), FAMS Dr Liu is a Consultant in the Department of Renal Medicine, SGH. She is a general nephrologist trained in various aspects of Nephrology including Chronic Kidney Disease, Glomerulonephritis, Dialysis, Intensive Care Nephrology and Transplantation Learning outcomes Upon completing the pre-readings and the lectures, you should be able to 1) Define renal failure and compare acute & chronic renal failure with regards to diagnosis, aetiology, pathophysiology, signs & symptoms, and possible complications 2) Describe the various management approach for patients with renal dysfunction - dialysis and renal transplant 3) Explain the impact of renal impairment on drug dosing & medical consideration Study resources Huether, S. E., & McCance, K. L. (2020). Understanding Pathophysiology (7th Ed.). New York: Elsevier Health Sciences. Cp 32: Alterations of renal and urinary tract function VanMeter, K. C., & Hubert, R. J. (2014). Gould's Pathophysiology for the Health Professions (5th Ed.). Philadelphia, PA: Saunders. Cp 18. Urinary System disorders National Registry of Diseases Office- Chronic Kidney Failure https://www.nrdo.gov.sg/publications/kidney-failure Hammer, G. D., & McPhee, S. J. (2019). Pathophysiology of Disease: An Introduction to Clinical Medicine (8th Ed). McGraw Hill Professional. Cp 16: Renal disease 1 1 Jan 2021 Pre-readings 1. Anatomy & Physiology Fluid regulation. The control of fluid balance is regulated by o Thirst mechanism in hypothalamus o Hormone: ▪ AntiDiuretic Hormone (ADH)– also known as vasopressin, promotes resorption of water into blood from kidney ▪ Aldosterone- determines resorption of sodium ions and water from kidney tubules, in response to fluid deficit in body o Atrial natriuretic peptide (ANP)- hormone synthesized by myocardial cells to reduce the workload of the heart by regulating fluid, Na + & K+ level Fluid excess/ oedema Oedema: an excessive amount of fluid in the interstitial compartment, which causes a swelling or enlargement of the tissues. Four mechanical causes of oedema (fluid excess in extracellular compartment) o Increase capillary hydrostatic pressure. E.g., high BP, hypervolemia, pregnancy, congestive heart failure o Decrease plasma osmotic pressure due to loss of plasma proteins. E.g., kidney disease lead to losing albumin through kidney, malnutrition or malabsorption, liver disease, extensive burns o Obstruction of lymphatic system. E.g., tumor or infective changes in lymph nodes o Increase capillary permeability. E.g., inflammatory response, bacterial toxin, large burn wounds Fluid deficit/ dehydration Fluid deficit can result from inadequate intake or excessive loss or a combination of both Losses are more common and affect the extracellular compartment first Common causes: o Vomiting & diarrhoea – loses both fluid & electrolytes & nutrients o Excessive sweating – loss Na & water o Diabetic ketoacidosis- fluid, electrolytes & glucose in urine o Insufficient fluid intake – infant, elderly or unconscious person 2 1 Jan 2021  Table 1. Comparison of Signs & Symptoms of fluid imbalance (fluid overload vs dehydration) Source: Van Meter (2014) p19 Kidney is the primary regulator of electrolyte balance, of esp. importance are the Na+, K+ and Ca++ Sodium Primary cation in the extracellular fluid (90% of solutes in extracellular fluid) Level is mainly controlled by the kidney through Aldosterone Functions: o Maintain extracellular fluid volume by osmotic pressure o Nerve conduction o Muscle contraction Hyponatremia Hypernatremia Causes o Excessive sweating, vomiting & o Insufficient ADH (result in large diarrhoea volume of diluted urine) o Hormonal imbalance o Watery diarrhoea (insufficient aldosterone, o Prolonged period of rapid adrenal insufficiency; excess respiration ADH secretion) o Early chronic renal failure o Excessive water intake S&S o Anorexia, nausea, cramps o Thirst o Fatigue, lethargy, muscle o Weakness, lethargy, agitation weakness o Oedema o Headache, confusion, seizures o Increase BP o Decrease BP 3 1 Jan 2021 Potassium Major intracellular cation (therefore low serum level) K+ level is influenced by o Aldosterone: control excretion of K+ in urine o Insulin: promote movement of K into cells o Acid-base balance: acidosis shift K+ out of cell into extracellular fluid (displaced by H+ ion that diffuse into cell) Hyperkalaemia Hypokalaemia Causes o Renal failure o Diarrhoea o Aldosterone deficit o Diuresis o Extensive tissue damage (crush o Excessive aldosterone or injury or burns) glucocorticoids o Prolonged sever acidosis o Decreased dietary intake o Treatment of diabetic ketoacidosis w insulin S&S o Cardiac dysrhythmias o Cardiac dysrhythmias o Muscle weakness, may o Impaired neuromuscular progress to paralysis function o Fatigue, nausea, paraesthesia o Paraesthesia o Anorexia & nausea o Respiratory muscle weakness in severe deficit Calcium An important extracellular cation Ca level is controlled by o Parathyroid hormone (PTH): low blood Ca stimulates PTH   Ca absorption from digestive tract & kidneys o Calcitonin o Vit D o Phosphate level o Acid base-: alkalosis decreases free Ca+ causing hypocalcaemia Hypercalcemia Hypocalcaemia Causes o Bone tumours o Hypoparathyroidism o Hyperparathyroidism o Malabsorption syndrome o Immobility o Deficient serum albumin o Excessive Ca intake o Alkalosis o Renal failure (retention of phosphate & lack of Vit D activation) S&S o Apathy. Lethargy o Tetany- involuntary muscle o Anorexia, nausea, constipation spams o Polyuria, thirst o Tingling fingers o Kidney stones o Mental confusion o Arrhythmias, o Arrhythmias o Increase BP 4 1 Jan 2021 Urine is formed through two key processes: filtration and reabsorption Filtration o When filtration pressure increase, more filtrate & urine is produced o Large volume of fluid passes from glomerular capillaries into the tubule (Bowman capsule) ▪ Wastes, nutrients, electrolytes, other dissolved substances get into tubule ▪ Cells and protein remain in the blood. Resorption o Occurs in tubules (3 parts- Proximal, loop of Henle and distal convoluted tubules) o Reabsorption of essential nutrients, water, and electrolytes into the peritubular capillaries o Control of pH and electrolytes o The resorption is controlled by hormones ▪ Antidiuretic hormone (ADH) Secreted by the posterior pituitary Reabsorb water in distal convoluted tubules and collecting ducts ▪ Aldosterone Secreted by adrenal cortex Na+ reabsorption in exchange for K+ or H+ ▪ Atrial natriuretic hormone Hormone from the heart o Reduces Na+ and fluid reabsorption Fig 2. Schematic illustration of urine formation (Van Meter 2014, p 494) 5 1 Jan 2021 2. Renal Failure In Singapore, 2.3% of the residents aged between 18 and 69 years old had renal impairment as defined by eGFR less than 60 mL/min/1.73m Acute renal failure Characterised by sudden onset with oliguria (reduced urine output) or anuria (no urine output) Always involved both kidneys Causes of acute renal failure o Severe, prolonged circulatory shock or heart failure o Nephrotoxins: Drugs, chemicals, or toxins causing tubule necrosis and blood flow obstruction o Mechanical obstruction (occasionally) by calculi, blood clots, tumors that block urine flow beyond kidneys Blood tests o Elevated serum urea nitrogen (BUN) and creatinine levels o Metabolic acidosis o Hyperkalemia Treatment o Identify and remove or treat primary problem - to minimize risk of necrosis and permanent kidney damage o Dialysis - to normalize body fluids and maintain homeostasis Chronic renal failure Gradual irreversible destruction of the kidneys over a long period of time Asymptomatic in early stages May result from o Chronic kidney disease o Congenital polycystic kidney disease o Systemic disorders o Low-level exposure to nephrotoxins over sustained period of time Decreased renal reserve o Decrease in GFR o Higher than normal serum creatinine levels o No apparent clinical symptoms Renal insufficiency o Decreased GFR to about 20% of normal o Significant retention of nitrogen wastes o Excretion of large volumes of dilute urine o Decreased erythropoiesis o Elevated blood pressure End-stage renal failure o Negligible GFR o Fluid, electrolytes, and wastes retained in body o Azotemia, Anemia, and Acidosis (three As) o All body systems affected o Marked oliguria or anuria o Regular dialysis or kidney transplantation to maintain patient’s life 6 1 Jan 2021 Stages of Chronic Kidney Disease based on level of kidney function (Renal association) CKD 1 Minimal loss of kidney function. Typically asymptomatic eGFR of 90–120ml/min/1.73m2 CKD 2 Mild to moderate loss of kidney function Typically asymptomatic eGFR 60-89 ml/min/1.73m2 CKD 3 Moderate to severe loss of kidney function Typically asymptomatic eGFR 30-59 ml/min/1.73m2 CKD 4 Severe loss of kidney function Complications such as anaemia, hypertension and abnormal blood levels of phosphorus, calcium and vitamin D eGFR 16-29 ml/min/1.73m2 CKD 5 Patients who are approaching or have reached End-stage Renal Disease (ESRD) eGFR < 15 ml/min/1.73m2 Serum creatinine ≥ 500 μmol/L Need renal replacement therapy (dialysis or transplant) Diagnostic tests o Anemia, acidosis, and azotemia are the key indicators of chronic renal failure. Treatment—all body systems are affected. o Difficult to maintain homeostasis of fluids, electrolytes, and acid-base balance o Drugs to stimulate erythropoiesis o Drugs to treat cardiovascular problems o Intake of fluid, electrolytes, protein must be restricted o Dialysis or transplantation Comparison of acute renal failure and chronic renal failure Characteristic Acute Renal Failure Chronic Renal Failure Causes Severe shock Nephrosclerosis Burns DM Nephrotoxins (massive Nephrotoxins (long term exposure) exposure) Acute bilateral kidney infection Chronic bilat kidney infection/ or inflammation inflammation Polycystic disease Onset Sudden, acute Slow, insidious Early signs Oliguria, increased serum urea Polyuria with dilute urine Anemia, Fatigue, Hypertension Progressive signs Recovery: increasing urine End-stage failure or uremia output Oliguria, acidosis, azotemia Prolong failure: uremia Source: Table 18-3, Van Meter 2014, p512 7 1 Jan 2021 3. Renal management Diuretic drugs Used to remove excess Na and water from the body Prescribed for many disorders: Renal disease, hypertension, edema, congestive heart failure, liver disease, pulmonary edema Several different mechanisms to increase urine volume based on specific drug There are 3 types of diuretics: Each type affects a different part of your kidneys and may have different uses Types of diuretic & Examples Indications mechanism Thiazide diuretics- Microzide treat hypertension Targets distal tubules (Hydrochlorothiazide) Loop diuretics – Lasix (Furosemide) treat fluid retention, heart targets loops of Henle failure & kidney disease Potassium-sparing – Aldactone treat heart failure, kidney targets collecting (Spironolactone) disease & liver disease tubules. Side effects of diuretics o Dizziness (orthostatic hypotension), dehydration o Excessive loss of electrolytes, may result in muscle weakness or cardiac arrhythmias o Hyponatremia (all types) o Hypokalaemia (Thiazide & Loop) , hence need K+ supplement When prescribing diuretics, it is important to check the use of drugs such as: o Antidepressants, particularly when taking thiazide or loop-acting diuretics o Cyclosporine, particularly if taking a potassium-sparing diuretic o Digitalis, particularly for patients with low potassium levels o Lithium o Insulin- thiazide and loop-acting diuretics can  blood sugar levels o Medications for high blood pressure Dialysis Renal dialysis is a procedure that substitute the normal kidney function of removing waste products and excess fluid from the body. 8 1 Jan 2021 Two main types of dialysis: haemodialysis and peritoneal dialysis, Haemodialysis Peritoneal dialysis Process blood moves from an Peritoneal membrane serves implanted shunt or catheter as the semipermeable (fistula) in an artery to membrane. Catheter with machine, and the blood entry and exit points is returned to body via veins implanted into the peritoneal cavity. Dialyzing fluid is instilled into cavity and drained via gravity. Frequency Usually required three times a Takes longer than week, Each last ~ 3 to 4 hrs. hemodialysis May be done at night (during sleep) or while patient is ambulatory Potential Shunt may become Infection resulting in peritonitis complications infected. Blood clots may form. Blood vessels involved in shunt may become sclerosed or damaged. Patient has an increased risk of infection Large fluctuation of electrolytes & fluid changes 9 1 Jan 2021