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Renal 24/03/2025 Tutors : Sneha and ShrutiLearning outcomes ▶ Kidney Functions ▶ Brief anatomy of the Kidneys and Lower Urinary Tract ▶ Mechanism of Micturition ▶ What is glomerular filtration and the associated pathologies ▶ Autoregulation of renal blood flow and RAAS ▶ What is the function of tubules and collecting ducts ▶ Renal Diseases and possible treatments ▶ Brief discussion on the development and congenital disorders of the urinary tract Kidney functions ▶ Filtration and reabsorption ▶ Filter blood through the glomerulus and removes waste products ▶ Reabsorb essential substances like glucose, amino acids and electrolytes ▶ Excretion ▶ Metabolic waste products, including urea, creatinine, and drugs, are eliminated in urine. ▶ Acid-base balance ▶ Regulate pH by excreting hydrogen ions and reabsorbing bicarbonate to maintain blood pH within a normal range ▶ Fluid and electrolyte balance ▶ Regulate blood volume and osmolarity by adjusting sodium, potassium, and water excretion under hormonal control Endocrine functions Secretes erythropoietin , renin and calcitrol Anatomy of kidneys ● Bilateral bean-shaped organs, located in the posterior abdomen ● Kidneys are encased in complex layers of fascia and fat. ● Renal parenchyma divided into outer cortex and inner medulla. The cortex extends into the medulla and divides into renal pyramids ● Urine passes through the major calices into the renal pelvis. From the renal pelvis, urine drains into the ureter, which transports it to the bladder for storage. ● The kidneys are supplied with blood via the renal arteries, which arise directly from the abdominal aorta and enter the kidneys via the renal hilum ● Renal artery segmental arteries interlobar arteries arcuate arteries interlobular arteries afferent arterioles ● The kidneys are drained of venous blood by the left and right renal veins. They leave the renal hilum anteriorly to the renal arteries, and empty directly into the inferior vena cava. Nephron ▶ Nephron is the functional unit of the kidney, and made of two main parts : the corpuscle and the renal tubule system ▶ Renal corpuscle is the filtration apparatus and consists of the Bowman’s capsule and the glomerulus ▶ The glomerulus is a network of capillaries formed by branches of the renal artery (afferent and efferent arterioles). ▶ The glomerular capsule surrounds the glomerulus. It consists of two layers (parietal and visceral), which bound a cavity called the glomerular capsular space (Bowman’s / urinary space).Renal tubule system ▶ The tubule system is the part of the nephron which processes glomerular ultrafiltrate into urine ▶ It consists of three parts : proximal tubule, Loop of Henle and distal tubule ▶ Proximal tubule is the first part of the tubular system and is composed of simple cuboidal epithelium, rich in mitochondria and microvilli (brush border) ▶ The Loop of Henle is the U-shaped bend of a nephron which extends through the medulla of the kidney and consists of two parts; thin descending and thin ascending limbs. Both limbs are composed of simple squamous epithelium ▶ The distal tubule is composed of simple cuboidal epithelium . Several distal convoluted tubules from neighbouring nephrons drain into a collecting duct which then travel through the kidney medulla, converging at the apex of each renal pyramid. ▶ Cortical collecting ducts are made of simple cuboidal epithelium and medullary collecting ducts are made of simple columnar epithelium Lower urinary tract ▶ The role of the bladder is to temporarily store urine and assists in the expulsion of urine ▶ Urine enters the bladder through the left and right ureters, and exits via the urethra. Internally, these orifices are marked by the trigone – a triangular area located within the fundus. The trigone walls are smooth compared to the rest of the internal bladder wall ▶ The bladder wall contains specialised smooth muscle – known as detrusor muscle to contract during micturition ▶ Arterial supply : superior vesical branch of the internal iliac artery. ▶ Venous drainage : vesical venous plexus, which empties into the internal iliac veins Mechanism of Micturition ▶ Bladder receives input from both the autonomic (sympathetic and parasympathetic) and somatic arms of the nervous system : ▶ Sympathetic – hypogastric nerve (T12 – L2). It causes relaxation of the detrusor muscle, promoting urine retention. Controls the internal urethral sphincter. ▶ Parasympathetic – pelvic nerve (S2-S4). Increased signals from this nerve causes contraction of the detrusor muscle, stimulating micturition. ▶ Somatic – pudendal nerve (S2-4). It innervates the external urethral sphincter, providing voluntary control over micturition.Bladder Filling Phase: ● The bladder fills with urine (produced by the kidneys). ● Stretch receptors in the bladder wall detect increasing volume. ● Sympathetic nervous system (T11-L2) keeps the detrusor muscle relaxed and the internal urethral sphincter contracted to store urine. Reflex Activation (Threshold Reached): ● When bladder volume reaches ~300–500 mL, stretch receptors send signals via pelvic nerves (S2-S4) to the pontine micturition center (PMC) in the brainstem. ● PMC initiates the micturition reflex when urination is appropriate. Voiding Phase: ● Parasympathetic activation (S2-S4): Contracts detrusor muscle and relaxes internal urethral sphincter. ● Somatic (voluntary) control: Pudendal nerve (S2-S4) relaxes external urethral sphincter for urination. CNS Control: ● The PMC and cerebral cortex allow voluntary control, enabling delay or initiation of urination. ● In infants or in neurological disorders, voluntary control may be impaired, leading to reflexive urination. Glomerular filtration ▶ The kidney filtration apparatus is formed by three layers of tissue; endothelium of the glomerular capillaries, glomerular basement membrane (GBM) and podocytes (visceral layer of renal capsule). ▶ Together, these three layers function as a selective filter, allowing only molecules below a certain size and charge, to pass from the blood and enter the renal tubular system. ▶ For example, blood cells, platelets, some proteins and some anions are prevented from leaving the glomerular capillaries, while water, glucose, amino acids, urea and inorganic ions can pass through; ▶ The remaining unfiltered blood is carried out of the glomerulus by the efferent arteriole, and passes back into the venous system. ▶ Pressurizedbloodenterstheglomerulusthrougharelativelywideafferentarteriole,butis forcedtoexitthroughanarrowerefferentarteriole.Thiscreateshydrostaticpressure(main drivingforce). ▶ Glomerular filtration rate (GFR) measures volume of filtrate formed per minute, critical for kidney function.Glomerulopathies ▶ Damage/inflammation to the glomeruli leads to increased permeability of the glomerular filtration barrier ▶ Endothelial cell damage and podocyte injury can lead to leakage of proteins and red blood cells into the urine (proteinuria and hematuria). ▶ Divided into nephritic and nephrotic syndromeAutoregulation of renal blood flow ▶ Renal blood flow is the volume of blood that reaches the kidneys per unit time and determines glomerular filtration rate ▶ Renal blood flow is regulated by increasing/decreasing the arteriolar resistance ▶ 2 main mechanisms : myogenic and tubuloglomerular ▶ Myogenic mechanism : smooth muscles cells in arterioles automatically contract when stretched by high blood pressure▶ Tubuloglomerular mechanism : High GFR detected in distal convoluted tubule stimulates macula densa cells to release adenosine, which increases resistance in the afferent arterioleRenin-angiotensin-aldosterone system (RAAS) ▶ Regulation of systemic blood pressure ▶ Decrease in arterial blood pressure causes decreased kidney perfusion , which is detected by chemoreceptors in macula densa. This causes juxtaglomerular cells to secrete renin, and activates RAAS.Question 1 Which structure carries urine from the kidneys to the bladder in the renal excretory system? A) Urethra B) Ureter C) Prostate gland D) Vas deferensWhich structure carries urine from the kidneys to the bladder in the renal excretory system? A) Urethra B) Ureter C) Prostate gland D) Vas deferensQuestion 2 Which structure in renal histology is primarily responsible for reabsorbing water and solutes from the filtrate, concentrating urine, and regulating electrolyte balance? A) Proximal convoluted tubule B) Glomerulus C) Collecting duct D) Renal papillaWhich structure in renal histology is primarily responsible for reabsorbing water and solutes from the filtrate, concentrating urine, and regulating electrolyte balance? A) Proximal convoluted tubule B) Glomerulus C) Collecting duct D) Renal papillaExplanation A) Proximal convoluted tubule: Responsible for reabsorbing water, ions, glucose, and other nutrients from the filtrate, concentrating urine, and regulating electrolyte balance. B) Glomerulus: Filters blood to form the initial urine filtrate. C) Collecting duct: Adjusts urine concentration and volume, reabsorbing water under hormonal influence. D) Renal papilla: Where urine from nephrons is emptied into the renal pelvis for elimination.Question 3 What are podocytes primarily known for in the kidney? A) Transport of nutrients from the glomerulus to the renal tubules B) Regulation of blood pressure within the glomerulus C) Maintenance of the filtration barrier in the renal corpuscle D) Production of hormones involved in water reabsorptionWhat are podocytes primarily known for in the kidney? A) Transport of nutrients from the glomerulus to the renal tubules B) Regulation of blood pressure within the glomerulus C) Maintenance of the filtration barrier in the renal corpuscle D) Production of hormones involved in water reabsorptionExplanation Podocytes are specialized cells in the kidney's glomerulus. They maintain the integrity of the glomerular filtration barrier, which selectively allows small molecules to pass into the urine while preventing larger ones, like proteins, from doing so. This selective filtration ensures proper kidney function.T ubular function ❑ Bowman’s capsule is connected to the proximal convoluted tubule (PCT)>> Loop of Henle (Descending thin)>>Loop of Henle (Ascending thick)>> Distal convoluted tubule (DCT)>>Collecting DuctProximal Convoluted T ubule ▶ Reabsorption of Sodium,Chloride, Potassium,Amino Acids, Glucose, Urea and Bicarbonate ▶ Sodium is reabsorbed together with glucose/amino acids into the cells then the glucose/amino acid is reabsorbed into circulation ▶ Next sodium is exchanged for hydrogen (cells) and sodium is reabsorbed into the circulation via the sodium potassium ATPase ▶ Bicarbonate reabsorption: Bicarb cannot be directly move into the cells and thus is converted to carbonic acid first ▶ Bicarb can be co transported into the circulation with sodium ▶ Secretion of: H+, NH3, Uric acid, creatinine, bile salts and drugsAscending Loop of Henle ▶ Reabsorption of Sodium,Chloride, Potassium ▶ Sodium, Chloride and Potassium and reabsorbed into the cell via the symporter ▶ Potasssium and chloride are reabsorbed via another symporter ▶ Sodium is reabsorbed via Na/K ATPase ▶ Passive channels between lumen and cell for sodium and potassiumDistal Convoluted T ubule and Collecting Duct ▶ Reabsorption of sodium, chloride, calcium, magnesium and bicarb ▶ Sodium and chloride reabsorbed via symport into the cells ▶ sodium reabsorbed via NA/K ATPase ▶ chloride reabsorbed via passive channels ▶ Magnesium and calcium via para cellular pathways ▶ Sodium reabsorbed and hydrogen is excreted ▶ Bicarbonate reabsorbed via bicarbonate chloride exchanger ▶ ENac in the apical surface to facilitate sodium reabsorption and potassium excretionCounter Current MultiplierNephrotic Syndrome and nephritic Concept: Nephrotic syndrome (NS) is a clinical syndrome defined by massive proteinuria (greater than 40 mg/m^2 per hour) responsible for hypoalbuminemia (less than 30 g/L), with resulting hyperlipidemia, edema, and various complications. It is caused by increased permeability through the damaged basement membrane in the renal glomerulus. ▶ Usually albumin should not be excreted out however with certain pathologies, albumin is excreted and leads to hypoalbumineria ▶ Hypoalbumineria leads to low oncontic Pa in the vessels leading to edema (into the interstitium) Concept: The nephritic syndrome is a clinical syndrome presenting as hematuria, hypertension, oliguria, and edema. It can be due to a primary renal disease or a clinical manifestation of other glomerular renal pathology. ▶ Acute inflammation of the kidney leading to blood in the urine RBC casts ▶ The kidney is unable to get rid of the fluid leading to increased fluid in the plasmaNephritic Syndrome Vs Nephrotic ▶Chronic Kidney Disease ▶ A progressive decline in renal function for >3 Montha ▶ Dertemined by Laboratory tests: ▶ reduced eGFR(<60ml/min/1.73m^2) AND ▶ markers of renal dysfunction ▶ Proteinuria/Haematuria ▶ Electrolyte abnormalities ▶ histological/structural changesCauses of Chronic Kidney Disease and testing methods ▶ High blood pressure is a significant risk factor for the development and progression of chronic kidney disease (CKD). however it often just coexists with CKD and is not the most common cause for CKD ▶ DM is usually the most common cause for CKD. High blood sugar can cause damage to the kidney’s blood vessels and structures leading to kidney disease 1. Urine Dipstick: Detects abnormalities like protein and blood in the urine but provide qualitative and not quantitative results 2. Urinary Albumin to Creatinine Ratio: This accurately quantifies proteinuria and is crucial for assessing kidney damage in CKD 3. Blood testing (Serum creatinine and electrolytes): They evaluate kidney function and electrolyte balance but do not directly measure proteinuria 4. Renal Ultrasound: This assesses kidney structure but doesn’t directly evaluate proteinuria or kidney damageManagement of CKD ▶ Lifestyle modifications ▶ Healthy Diet, low in salt, potassium and phosphorus ▶ regular exercise, weight managenent and quitting smoking ▶ Limiting alcohol intake ▶ Medications ▶ ACE inhibitors and ARB (BP medications) ▶ Managing complications like anaemia and high cholesterol ▶ Phosphate binders to control phosphorus levels ▶ Managing Underlying conditions ▶ diabetes ▶ hypertension ▶ Dialysis and Transplant ina advances stagesAcute Kidney Injury ▶ Sudden loss of renal function <3 months ▶ Categories ▶ Pre-Renal (~60%) ▶ Renal (~35%) ▶ Post renal (~5%) Diagnostic Criteria: ▶ Rise in creatinine of 26 or more over 48H ▶ 50% or more rise in baseline creatinine values (lowest value of past 3 months) ▶ Fall in urine output to less that 0.5ml/kg/hr for more than 6 hours in adults ▶ 25% or more fall in eGFR in children/young adults in 7 DaysFeatures of AKI ▶ oliguria/anuria ▶ signs of volume depletion ( reduced skin turgor, hypotension, dry mucous) ▶ signs of fluid overload (Peripheral edema, HF) ▶ Signs of uraemia (Urea and other waste products in blood) ▶ Encephalopathy ▶ Nausea ▶ Pericarditis ▶ Signs of renal obstruction ▶ Distended bladderManagement of AKI ▶ ALL ▶ Stop exacerbating medications ▶ Diuretics ▶ NSAIDs ▶ Aminoglycosides ▶ Pre Renal ▶ Check volume status and give fluids ▶ Intrarenal ▶ Treat underlying cause and supportive care ▶ Post renal ▶ find and treat blockageKey Congenital Disease 1. Congenital Polycystic kidney a. collecting ducts surrounded by cysts of undifferentiated cells b. failure of development of nephrons to join collecting ducts c. Formation of cysts ar rudimentary nephrons d. Often the PCT is malformed i. Hyperplasia of tubule epithelium causing blockage ii. Dilatation of tubule lumen due to abnormal differentiation of tubule cells A. Autosomal dominant (ADPKD) a. Cysts from all parts of nephron b. more common 1:1000 c. Cysts over renal tubules later expand to cavities of different sizes d. Mutation in PKD1/PKD2 in chromosome 16 e. 40-50Y, flank pain, High BP, Cysts in liver, pancreas and lungs, prone to aneurysms B. Autosomal recessive a. Progressive disorder b. Multiple cysts from collecting tubule (medulla) c. renal failure in first decade of lifeKey Congenital Disease 1. Horseshoe kidney a. IMA artery blocking ascent b. Both kidneys fused at lower pole c. pelvic pancake if both poles fused ▶ Kidney starts of function in 2nd trimester bur only reaches maturity at 26 weeks ▶ oligohydramnios (Dilute urine in amniotic fluid) ▶ foetus swallows reflexly 2. Renal Agenesis a. Bilateral 1:10000 b. Unilateral > No symptoms i. Cause: Genetic/Environmental factors or Untreated diabetes of mother c. Accompanied by i. esophageal atresia ii. anorectal atresia iii. hypoplastic lung iv. absent sex organsQuestions A 65-year-old woman presents with CKD. Her eGFR is currently measured at 28 ml/min/1.73m2. What stage of CKD is she currently at? • A) Stage 5 • B) Stage 2 • C) Stage 4 • D) Stage 3bQuestions A 65-year-old woman presents with CKD. Her eGFR is currently measured at 28 ml/min/1.73m2. What stage of CKD is she currently at? • A) Stage 5 • B) Stage 2 • C) Stage 4 • D) Stage 3bQuestions What is the most common cause of chronic kidney disease (CKD)? • A) Hypertension • B) Glomerulonephritis • C) Polycystic kidney disease • D) Diabetes mellitusQuestions Which of the following diagnostic tests is most useful for assessing kidney damage and determining the severity of proteinuria in chronic kidney disease (CKD)? • A) Urine dipstick • B) Urinary albumin-to-creatinine ratio • C) Blood tests (serum creatinine and electrolytes) • D) Renal ultrasoundQuestions Which of the following diagnostic tests is most useful for assessing kidney damage and determining the severity of proteinuria in chronic kidney disease (CKD)? • A) Urine dipstick • B) Urinary albumin-to-creatinine ratio • C) Blood tests (serum creatinine and electrolytes) • D) Renal ultrasoundQuestions Which of the following conditions is characterized by a sudden decrease in kidney function, resulting from factors such as dehydration, hemorrhage, or decreased blood flow to the kidneys? • A) Pre-renal AKI • B) Post-renal AKI • C) Renal AKIQuestions Which of the following conditions is characterized by a sudden decrease in kidney function, resulting from factors such as dehydration, hemorrhage, or decreased blood flow to the kidneys? • A) Pre-renal AKI • B) Post-renal AKI • C) Renal AKIQuestions A 60-year-old male presents to the emergency department with complaints of fatigue, nausea, and decreased urine output over the past 24 hours. He has a history of hypertension and type 2 diabetes mellitus, for which he takes medications. On examination, he appears lethargic with dry mucous membranes and mild pedal edema.Question:Based on the clinical presentation, which of the following criteria would be most indicative of acute kidney injury (AKI) in this patient? • A) Rise in serum creatinine by 5% within 24 hours • B) Rise in serum creatinine of 10% within 72 hours • C) Fall in urine output to less than 0.5 ml/kg/hr for more than 6 hours in adults • D) Fall in estimated glomerular filtration rate (eGFR) by 20% within 5 daysQuestions A 60-year-old male presents to the emergency department with complaints of fatigue, nausea, and decreased urine output over the past 24 hours. He has a history of hypertension and type 2 diabetes mellitus, for which he takes medications. On examination, he appears lethargic with dry mucous membranes and mild pedal edema.Question:Based on the clinical presentation, which of the following criteria would be most indicative of acute kidney injury (AKI) in this patient? • A) Rise in serum creatinine by 5% within 24 hours • B) Rise in serum creatinine of 10% within 72 hours • C) Fall in urine output to less than 0.5 ml/kg/hr for more than 6 hours in adults • D) Fall in estimated glomerular filtration rate (eGFR) by 20% within 5 daysQuestions Case:A 50-year-old male presents to the clinic with complaints of uncontrolled hypertension despite taking multiple antihypertensive medications. He also reports episodes of flash pulmonary oedema and worsening kidney function over the past few months. On examination, he has elevated blood pressure and mild ankle oedema. • Question: Based on the clinical presentation and medical history, which of the following pathophysiological mechanisms is most likely contributing to the patient’s symptoms? • A) Acute tubular necrosis (ATN) due to recent exposure to nephrotoxic medications • B) Glomerulonephritis secondary to untreated streptococcal infection • C) Renal artery stenosis causing decreased renal perfusion • D) Diabetic nephropathy leading to progressive kidney damageQuestions Case:A 50-year-old male presents to the clinic with complaints of uncontrolled hypertension despite taking multiple antihypertensive medications. He also reports episodes of flash pulmonary oedema and worsening kidney function over the past few months. On examination, he has elevated blood pressure and mild ankle oedema. • Question: Based on the clinical presentation and medical history, which of the following pathophysiological mechanisms is most likely contributing to the patient’s symptoms? • A) Acute tubular necrosis (ATN) due to recent exposure to nephrotoxic medications • B) Glomerulonephritis secondary to untreated streptococcal infection • C) Renal artery stenosis causing decreased renal perfusion • D) Diabetic nephropathy leading to progressive kidney damageFeedback Please take a minute now before you leave to fill in a quick feedback form! https://app.medall.org/event-listings/aim-y2-tutorial-renal Thank you for coming! ▶ If you have any more questions, feel free to email me at s2752533@ed.ac.uk or email accessibilityinmedicine@gmail.com ▶ Give our Facebook page a like for updates and opportunities, just search @AIMEdinburghSign up to the mailing list ▶ Sign up to the AIM mailing list to be the first to hear about tutorials, discounts, and opportunities!