MED407 — Nephrology I: Lecture Note

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Course code: MED 407 Course title: Nephrology I Course credit load: 2 Units Series 1: Fundamentals of Nephrology and Clinical Skills • Part 1.1: Overview of Renal Anatomy and Physiology o Sub Part 1.1.1: Gross anatomy and microstructure of the kidney o Sub Part 1.1.2: Glomerular filtration and tubular function o Sub Part 1.1.3: Renal regulation of fluid, electrolyte, and acid-base balance • Part 1.2: Assessment of Renal Function o Sub Part 1.2.1: Glomerular filtration rate and its estimation o Sub Part 1.2.2: Urinalysis and urine microscopy in renal disease o Sub Part 1.2.3: Blood tests and imaging in renal evaluation • Part 1.3: The Clinical Approach to the Patient with Renal Disease o Sub Part 1.3.1: Renal history taking o Sub Part 1.3.2: Physical examination in renal disease o Sub Part 1.3.3: Clinical syndromes in nephrology • Part 1.4: Acute Kidney Injury and Chronic Kidney Disease — An Introduction o Sub Part 1.4.1: Definition and classification of acute kidney injury

o Sub Part 1.4.2: Definition and staging of chronic kidney disease o Sub Part 1.4.3: Overview of the clinical consequences of kidney disease Introduction The kidneys perform functions of fundamental importance to homeostasis: filtering the blood to remove metabolic waste products, regulating the volume and composition of body fluids, maintaining acid-base balance, and producing hormones including erythropoietin and activated vitamin D. Renal disease is prevalent in Nigeria and sub-Saharan Africa, where conditions such as hypertension, diabetes mellitus, glomerulonephritis, and infections contribute to a high burden of both acute and chronic kidney disease. This Series provides the foundational knowledge required for all subsequent study of nephrology. It covers the anatomy and physiology of the kidney, the assessment of renal function through laboratory and imaging investigations, the clinical approach to history taking and examination in a patient with suspected renal disease, and the clinical syndromes that define the major presentations of kidney disease. It concludes with an introduction to acute kidney injury and chronic kidney disease as the two overarching clinical frameworks within which most renal disease is managed. A solid understanding of these fundamentals is the prerequisite for recognising, investigating, and managing the specific renal conditions covered in subsequent Series of this course. Series Learning Outcomes Upon completing this Series, you should be able to: • SLO 1.1 describe the gross anatomy, microstructure, and major physiological functions of the kidney (Linked to Part 1.1),

• SLO 1.2 explain glomerular filtration and the tubular mechanisms regulating fluid, electrolyte, and acid-base balance (Linked to Part 1.1), • SLO 1.3 describe the investigations used to assess renal function including GFR estimation, urinalysis, urine microscopy, blood tests, and imaging (Linked to Part 1.2), • SLO 1.4 conduct a focused clinical assessment of a patient with suspected renal disease and identify the major clinical syndromes of nephrology (Linked to Part 1.3), and • SLO 1.5 define acute kidney injury and chronic kidney disease, state their classification systems, and describe the clinical consequences of kidney disease (Linked to Part 1.4). 1.1 Overview of Renal Anatomy and Physiology 1.1.1 Gross anatomy and microstructure of the kidney The kidneys are paired retroperitoneal organs, each weighing approximately 150 g and measuring 11 to 12 cm in length. Each kidney is composed of an outer cortex (containing the glomeruli, proximal and distal tubules) and an inner medulla (containing the loops of Henle and collecting ducts). The medulla is organised into renal pyramids whose apices (papillae) drain urine into the minor calyces, major calyces, renal pelvis, and ureter. The functional unit of the kidney is the nephron, of which there are approximately one million per kidney. Each nephron consists of a glomerulus (a tuft of capillaries enclosed in Bowman's capsule, responsible for ultrafiltration), a proximal convoluted tubule, the loop of Henle (descending and ascending limbs; generates the medullary osmotic gradient), a distal convoluted tubule, and a collecting duct. The glomerular filtration barrier consists of fenestrated endothelium, glomerular basement membrane, and podocyte foot processes (visceral epithelium). Fill in the blank: Each kidney contains approximately one million nephrons; the nephron consists of the glomerulus, proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct; the glomerular filtration barrier comprises endothelium, basement membrane, and ________ foot processes.

1.1.2 Glomerular filtration and tubular function Glomerular filtration produces approximately 180 litres of ultrafiltrate per day by driving plasma water and solutes across the filtration barrier; large proteins and blood cells are normally retained. The filtrate is then modified by the tubules: the proximal tubule reabsorbs approximately 65 percent of filtered sodium, water, glucose, amino acids, bicarbonate, and phosphate; the loop of Henle creates the medullary osmotic gradient essential for urine concentration; and the distal tubule and collecting duct perform fine regulation of sodium, potassium, and water under the control of aldosterone and antidiuretic hormone (ADH). The kidneys produce approximately 1 to 2 litres of urine per day from 180 litres of filtrate, concentrating urine up to a maximum osmolality of approximately 1200 mOsm/kg. The kidneys also perform important endocrine functions: producing erythropoietin (stimulating red cell production), renin (activating the RAAS to regulate blood pressure and sodium balance), and converting vitamin D to its active form 1,25-dihydroxycholecalciferol (calcitriol) (essential for calcium absorption and bone mineralisation). Fill in the blank: The proximal tubule reabsorbs 65 percent of filtered sodium, glucose, and bicarbonate; the loop of Henle creates the medullary osmotic gradient; the collecting duct regulates water under the control of ________; the kidneys produce erythropoietin, renin, and calcitriol. 1.1.3 Renal regulation of fluid, electrolyte, and acid-base balance Fluid balance is regulated by the kidney through sodium and water handling: aldosterone promotes sodium reabsorption in the distal tubule and collecting duct; ADH promotes water reabsorption in the collecting duct; and atrial natriuretic peptide (ANP) promotes sodium excretion. These hormones collectively maintain intravascular volume and plasma osmolality within narrow physiological ranges. Acid-base balance is maintained by the kidney through three mechanisms: bicarbonate reabsorption in the proximal tubule (regenerating consumed buffer), ammonium excretion (the kidneys generate ammonium from glutamine, providing an additional proton-accepting

mechanism), and titratable acid excretion (phosphate buffers in the tubular fluid accept protons). In renal failure, all three mechanisms are impaired, resulting in metabolic acidosis — one of the most important complications of advanced kidney disease. Fill in the blank: The kidney maintains acid-base balance through bicarbonate reabsorption, ammonium excretion, and titratable acid excretion; in renal failure these mechanisms fail, resulting in metabolic ________. Figure 1.1: Renal anatomy, nephron structure, and the major functions of the kidney Pilot questions 1.1 1. Describe the gross anatomy and internal structure of the kidney. (Linked to SLO 1.1) 2. Describe the components of the nephron and the function of each segment. (Linked to SLO 1.1) 3. Explain glomerular filtration, including the structure of the filtration barrier. (Linked to SLO 1.2)

4. Describe the endocrine functions of the kidney. (Linked to SLO 1.2) 5. Explain how the kidney maintains acid-base balance. (Linked to SLO 1.2) 1.2 Assessment of Renal Function 1.2.1 Glomerular filtration rate and its estimation Glomerular filtration rate (GFR) is the volume of plasma filtered by the glomeruli per unit time, normally 90 to 120 mL/min per 1.73 m² in adults. GFR is the best single measure of overall kidney function; as nephrons are lost, GFR falls proportionally. True GFR is measured by inulin clearance (gold standard) or radiolabelled markers, but these are impractical for routine clinical use. Estimated GFR (eGFR) is calculated from serum creatinine using equations such as the CKD-EPI equation or the older MDRD equation, which incorporate age, sex, and ethnicity to account for variation in muscle mass (creatinine is a product of creatinine phosphate metabolism in muscle). Serum creatinine alone is a poor indicator of early renal impairment: due to tubular secretion and the fact that serum creatinine does not rise above the normal range until approximately 50 percent of GFR is lost. Serum cystatin C is an alternative marker less dependent on muscle mass, useful in elderly, malnourished, or amputee patients. Fill in the blank: GFR is normally 90 to 120 mL/min per 1.73 m²; eGFR is estimated from serum ________ using the CKD-EPI or MDRD equation; serum creatinine does not rise above normal until approximately 50 percent of GFR is lost. 1.2.2 Urinalysis and urine microscopy in renal disease Urinalysis provides rapid diagnostic information about renal and urinary tract disease. Key dipstick findings in renal disease include: proteinuria (glomerular damage, nephrotic syndrome, or tubular dysfunction), haematuria (glomerulonephritis, urinary tract infection, calculi, malignancy), leucocyte esterase and nitrites (urinary tract infection), and glucosuria without hyperglycaemia (proximal tubular dysfunction, Fanconi syndrome). Urine protein quantification

is performed by the urine albumin-to-creatinine ratio (uACR) or 24-hour urine protein collection. Urine microscopy provides critical diagnostic information in renal disease. Red blood cell casts (dysmorphic red cells aggregated in a cylindrical cast formed in the tubule lumen) are pathognomonic of glomerulonephritis. Granular casts indicate tubular injury. Waxy or broad casts indicate advanced chronic kidney disease with dilated tubules. Dysmorphic red blood cells (acanthocytes) suggest glomerular origin of haematuria, distinguishing it from lower urinary tract bleeding. Fill in the blank:

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