Renal Disease Lecture Notes PDF

Renal Disease BIOL 22041 – Clinical Biochemistry Dr Sergio Colombo Learning Outcomes (LO) ▪ After this lecture you will be able to: ▪ Critically describe the normal biochemistry/physiology of the kidneys ▪ Anatomy ▪ Renal Function ▪ Assessment of functionality ▪ Identify and explain Acute and Chr...

Renal Disease BIOL 22041 – Clinical Biochemistry Dr Sergio Colombo Learning Outcomes (LO) ▪ After this lecture you will be able to: ▪ Critically describe the normal biochemistry/physiology of the kidneys ▪ Anatomy ▪ Renal Function ▪ Assessment of functionality ▪ Identify and explain Acute and Chronic Kidney Disease, describing the biochemical basis of the disease, and the biochemistry used to diagnose and monitor the disease. ▪ K1. Critically understand the principles of biochemical testing in the diagnosis, treatment and monitoring of common conditions including diabetes, thyroid disease, myocardial infarct, gout, renal failure and liver disease. ▪ K3. Understand the limitations of biomarkers as detection and prognosis tools and, the importance of differential diagnosis in Clinical Biochemistry. The Kidneys ▪ A paired organ system ▪ High blood supply (approximately 20% of the cardiac output, or 1000 mL/min) ▪ Plasma filtering organ ▪ Nephrons: functional units ▪ Any damage to these nephrons can result in kidney failure ▪ Hormonal functions ▪ Urine generation Kidney Anatomy Proximal Convoluted Tubule Renal Cortex Glomerulus Nephron Distal Convoluted Tube From Renal Artery Renal Medulla Renal Artery To Renal Vein Renal Vein Collecting Duct Ureter Renal capsule Nephron Kidney Anatomy (2) Glomerular Cell Composition Glomerular Membrane Structure Functions Of The Kidneys Calcitriol (active Vit D) Mechanisms Of Renal Tubular Transport Mechanisms Of Renal Tubular Transport (2) Lumen Cells Interstitium Mechanisms Of Renal Tubular Transport (3) Mechanisms Of Renal Tubular Transport H2O Glucose Na+ K+ Aminoacids ClHCO3- / Phosphate Impermeable to H2O (Loop of Henle) Na+ K+ ClHCO3Ca2+ Renal Glucose Reabsortion Functions Of The Kidneys: Renin Renin – Angiotensin - Aldosterone System Functions Of The Kidneys: Erythropoietin (Epo) Tests To Assess Renal Function ▪ Urine tests ▪ Blood tests ▪ Assessment of glomerular and tubular function Urinalysis Urinary Examination: Reagent Strip ‘Dipstick’ Testing ▪ Point of care ▪ Easy to use ▪ White blood cells ▪ Haemoglobin ▪ Glucose ▪ Protein Urea ▪ Urea is synthesized in the liver, primarily as a by-product of the deamination of amino acids ▪ Diffuse completely freely through membranes, removal depend on water, but it is also reabsorbed ▪ Urea levels can be affected in a number of situations e.g. urea production is increased by a high protein intake and decreased by a low protein intake In view of this it is important to consider extra-renal influences on urea concentrations before concluding that renal impairment is the cause of a altered result Creatinine ▪ Creatinine is a metabolic by-product of muscle metabolism (it is derived from creatine and phosphocreatine) ▪ It is filtered and excreted by the kidney therefore it’s concentration is inversely related to the Glomerular Filtration Rate (GFR) ▪ (A high creatinine indicates that glomerular function is impaired i.e. the GFR is low) Potassium ▪ The most common cause of a high potassium level is kidney disease (e.g. hyperkalaemia) ▪ Causes abnormal heart rhythms (potentially fatal) Reference Ranges ▪ Urea 2.5-8.0 mmol/L (mM) ▪ Creatinine 40-130 µmol/L (uM) ▪ Sodium 135-145 mmol/L (mM) ▪ Potassium 3.5-4.0 mmol/L (mM) Glomerular Function ▪ Glomerular filtrate is an ultra filtrate of plasma (like plasma but almost free of proteins) ▪ 120-140 ml/minute of glomerular filtrate is produced in normal individuals ▪ Urine is produced from the filtrate by selectively reabsorbing metabolically useful materials back into the capillaries surrounding the tubules or secreting other substances such as toxins into it from the capillaries ▪ Adequate glomerular function is important to maintain fluid/electrolyte/pH balance ▪ It is affected by blood pressure, number and area covered by nephrons. Assessment Of Glomerular Function This is carried out by performing tests in the clinical biochemistry laboratory: ▪ Urea ▪ Creatinine ▪ Electrolytes (sodium and potassium) ▪ Creatinine clearance test ▪ (GFR) Estimation Of Glomerular Filtration Rate (GFR) Glomerular filtration rate is the volume of plasma from which a given substance is completely removed in a unit of time ▪ Estimation of the efficiency with which substances are cleared from the blood by glomerular filtration and thus, a measure of nephron function ▪ The GFR is widely accepted as the best overall measure of kidney function ▪ A decrease in GFR precedes renal failure (all forms of CKD) ▪ Measurement of GFR can be used to monitor treatment, progression and predict the point at which renal replacement therapy is needed GFR: interpretation ▪ Assessed by measuring the clearance of a substance by the kidneys. ▪ The amount of Substance filtered is equal to the GFR x [PS] plasma ▪ The amount of Substance excreted is equal to [US] x urinary flow rate (V, volume per unit of time) GFR x [PS] = [US] x V Then GFR = [US] x V / [PS] Proteinuria As An Indicator Of Glomerular Function ▪ The glomerular basement membrane prevents filtration of large proteins from happening ▪ A small amount of albumin and other proteins can be found in urine ▪ Larger amounts indicate kidney damage ▪ 24 hour urine tests are then performed ▪ Albumin excretion in the range of 25-300 mg/24 hours is termed microalbuminuria Imaging And Renal Biopsy ▪ Biochemical tests of renal function are not the only tests available to the physician ▪ Other tests include ultrasound, computerized tomography (CT), magnetic resonance imaging (MRI), isotope scanning and renal biopsy ▪ Changes in shape of the kidney can detect renal disease ▪ Malignancies can also be detected (e.g. renal cell carcinoma) Revision ▪ Kidney Structure ▪ ▪ ▪ ▪ Functional structure: nephron Secretion – Excretion - Hormonal function Ultrafiltrate: glucose, aminoacids, ions, HCO3-/Phosphate Test to assess function (Urea, Creatinine, Ions, urine properties, blood test, limitations of biomarkers) ▪ GFR – definition and use Recommended Literature ▪ Chapter 3 – Clinical Biochemistry, Nessar Ahmed (2010) – Oxford. ▪ Chapter 7-8 – Clinical Biochemistry, Metabolic and clinical aspects, Marshall and Bangert (2008) Churchill Livingstone Elsevier.