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PRECILINCAL LECTURE SERIES Renal Physiology Jasmine LimbuLecture Contents Renal Anatomy Renal function Common Renal pathologies A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K H A B I C D E J F L G K HThe BladderStorage of urine (around 400-600mls) Expulsion of urineWhat cells make up the epithelium of the bladder? A) Cuboidal B) Columnar C) Simple D) Transitional E) SquamousWhat cells make up the epithelium of the bladder? A) Cuboidal B) Columnar C) Simple D) Transitional E) SquamousLayers of the bladder - Transitional epithelium - Lamina propria - Smooth muscle (Detrusor) - Loose connective tissueNerves The Detrusor muscle receives both sympathetic (hypogastric n.) and parasympathetic (pelvic n.) innervation. Hypogastric n = relaxes detrusor muscle + urine retention Pelvic n = contracts detrusor muscle + micturition Pudendal n = external urethral sphincter (voluntary control)Bladder stretch reflex (this is what happens in infants before toilet training) Bladder gets filled up --> walls stretch --> signals go to spinal cord --> then to parasympathetic fibres ---> through the pelvic nerve --> contracts detrusor muscle --> micturition Vessels: internal iliac vessels --> superior vesical arteries --> bladder --> vesical venous plexus --> interanal iliac veins Sphincter: Internal --> males have circular smooth fibres (prevents regurgitation of semen during ejaculation) + involuntary control. females have no muscle. External --> Skeletal muscle + voluntary control Bladder pathologies: - Cystitis - Urge incontinence - Stress incontinence - Overflow incontinence - Neurogenic incontinence - Bladder cancerThe Kidneys What are the different functions of the kidneys ?Excretion of waste Acide-Base balance Ion regulation Hormone production (EPO, Calcitrol, Renin) BP regulation Glucose regulationRetroperitoneal position (remember SAD PUCKER) T12 -L3 Outside of the kidneys: Renal capsule - -> Perirenal fat --> Renal Fascia --> pararenal fat Renal cortex Renal Medulla (renal pyramids) Renal Papilla (minor & major calyces)Suprarenal glands Aorta Duodenum Pancreas Ureters Colon Kidneys Eosophagus RectumThe Nephron The renal corpuscle: glomerulus + bowman capsule Production of filtrate. via ULTRAFILTRATION (aka filtration under pressure) Pressure created by constriction of efferent arteriole. In males = 180L/day In females = 150L/day Proximal convoluted tubule Secretion (what is going into the Cuboidal epithelial cells + brush lumen of the PCT from blood) borders Organic acids & bases (bile salts, Reabsorption with bulk transport: oxalate, catecholamines, other 65% of H20 in filtrate waste products of metabolism) H+ (helps drive bicarb back into Na, Cl, K 100% of the glucose in filtrate blood) 100% of the amino acids in filtrate Drugs & toxins 85-90% of bicarbonate in filtrate3 Na+ out & 2 K+ in to the cell via Na/K ATPase. Decreases Na+ in cell so... Na+ & Glucose (sodium/glucose cotransporter 2 SGLT2) both into the cell & then into blood. Same is done for amino acids. Reabsorption by diffusion: Urea, fat- soluble substances, H20 (due to higher conc of solutes in interstitial fluid), Cl-, K+ Na+/H+ antiporter: H+ into lumen & Na+ into the cells. (makes urine acidic) Descending loop of Henle Passive h20 reabsorption via aquaporin-1 channels. Driven by counter current multiplier system. V little urea, Na+, & other ion reabsorption. Water absorbed by the vasa recta Impermeable to salts Permeable to water Ascending loop of henle Impermeable to water Permeable to NaCl in thin section Active pumping of NaCl in thick section (includes the Na-K-Cl cotransporter (NKCC)) Decrease in filtrate osmolarity due to salt leaving. Distal convoluted tubule Active reabsorption & secretion of ions (Na, Ca, Cl) via Na+/K+ ATPase & other symporters (e.g. Na+-Cl- symporter) Impermeable to water Macula densa = located in first segment of DCT. Channels: sodium-chloride cotransporter (NCC) sodium-calcium antiporter (NCX) = Na+ into cell & Ca2+ Out into lumen. Parathyroid hormone increases the number of calcium channels, increasing reabsorption. Ca2+ Moves from lumen into cells into blood. Macula densa Juxtaglomerular apparatus: JG cells in afferent & efferent arterioles: senses low pressure & releases renin. Macula densa cells in DCT: if blood pressure is low then macula densa releases adenosine ---> vasoconstriction of the afferent arteriole ---> decreasing GFR ---> less filtration, more volume in blood --> increasing BP. Collecting duct Principal cells : Na+/K+ ATPase (Na out of cell into blood, K+ into cell). The K+ eventually leaves cell & into the lumen via uniporter. Intercalated cells: Type A = hydrogen-ATPase & H+/K+-ATPase. Secreting more H+ into lumen & reabsorbing HCO3-. The H+ in the lumen binds with phosphate or ammonia. K+/Cl- in bsolateral membrane allows K+ & Cl- to leave cell and go into the extracellular fluid. Type B = HCO3- channels to secrete HCO3- & has H+ channels to reabsorb H+ in response to alkalosis. ADH Anti-diuretic hormone produced in the hypothalamus & stored in the posterior pituitary gland. Increases number of aquaporin 2 ADH + V2 receptors ---> adenylyl cyclase activated --> lots of cyclic AMP produced --> causes vesicles with aquaporin 2 channels to deposite contents to apical membrane. More water reabsorbed.DiureticsCarbonic anhydrase inhibitor e.g. Acetazolamide Inhibits the reabsorption of HCO3- in the PCT (very weak diuretic) Side effects: Hypokalaemia Metabolic acidosisLoop diuretic= e.g. furosemide & bumetanide. Inhibits Na-K-Cl cotransporter (NKCC) in the thick ascending limb (less salt in the medulla, less water reabsorbed in the descending loop of henle) Indications: Heart failure, Resistant hypertension Adverse effects: Hypotension, hyponatraemia, hypokalaemia, hypoomagnesaemia, hypochloraemia, hypocalcaemia, renal impairment, gout, ototoxicity May need to increase dose in those with low GFR. Thiazide diuretics e.g. bendroflumethiazide Thiazide-like diuretics e.g. indapamide Inhibits sodium reabsorption at the DCT by blocking thiazide-sensitive Na+-Cl- symporter. More sodium in the filtrate and as this reaches the collecting duct this causes K+ loss (via principle cells) in the collecting duct (Hypokalaemia a major side effect). Common adverse effects: dehydration postural hypotension hyponatraemia, hypokalaemia, hypercalcaemia* gout impaired glucose tolerance (Na-Glu channel) impotence Rare adverse effects thrombocytopaenia agranulocytosis photosensitivity rash pancreatitis Potassium-sparing diuretics - Sodium channel blockers e.g. amiloride & triamterene - Aldosterone antagonists e.g. spironolactone & eplerenone Caution: hyperkalaemia risk in patients already on ACE inhibitors Sodium channel blockers = block epithelial sodium channel in collecting duct . Aldosterone antagonists = acts in cortical collecting duct. Inhibits aldosterone- mediated reabsorption of Na+ & secretion K+. So more Na+ in filtrate & more K+ in cells & blood stream.SGLT2 inhibitors Empagliflozin Dapagliflozin Canagliflozin Used to treat T2DM Inhibition of SGLT2 in the PCT. Therefore decreasing the reabsorption of glucose from the lumen into the blood. Glucose remains in the filtrate aka urine. Advantages = weight loss decreases CVD risk Adverse effects = UTI & Thrush AKI DKARenal toxic drugsDrugs to stop in AKI: (DAAAN) - Diuretics - ACE inhibitors - Angiotensin II - Aminoglycosides - NSAIDS Renal pathologiesRenal Stones Renal Cancer ADPKD Renal artery stenosis Nephrotic syndromes Nephritic syndromes Acute interstitial nephritis Renal tubular acidosis Hydronephrosis Nephroblastoma Urethral stricture AKI & CKD HUS PyelonephritisNephritic vs Nephrotic syndrome Nephritic = Haematuria Nephrotic = ProteinuriaSBASMr W presents to A&E with a suprapubic pain & a mass is felt on palpation. It is suspected that he has severe urine retention. What nerve when stimulated causes urine retention ? A) Pudendal n B) Iliac n C) Femoral n D) Hypogastric n E) Pelvic nMr W presents to A&E with a suprapubic pain & a mass is felt on palpation. It is suspected that he has severe urine retention. What nerve when stimulated causes urine retention ? A) Pudendal n B) Iliac n C) Femoral n D) Hypogastric n E) Pelvic nWhich of the following is NOT a function of the kidneys? A) Calcium homeostasis B) Blood pressure regulation C) Acid-Base balance D) Glucagon homeostasis E) Erythropoietin productionWhich of the following is NOT a function of the kidneys? A) Calcium homeostasis B) Blood pressure regulation C) Acid-Base balance D) Glucagon homeostasis E) Erythropoietin productionWhich structure is this arrow pointing too? A) Renal pelvis B) Major Calyx C) Ureter D) Renal medulla E) Renal CortexWhich structure is this arrow pointing too? A) Renal pelvis B) Major Calyx C) Ureter D) Renal medulla E) Renal CortexWhich of the following is a NOT a retroperitoneal structure? A) Spleen B) Aorta C) Duodenum D) Pancreas E) UreterWhich of the following is a NOT a retroperitoneal structure? A) Spleen B) Aorta C) Duodenum D) Pancreas E) UreterWhere in the nephron is calcium reabsorbed? A) PCT B) Descending loop of henle C) Ascending loop of henle D) DCT E) Collecting ductWhere in the nephron is calcium reabsorbed? A) PCT B) Descending loop of henle C) Ascending loop of henle D) DCT E) Collecting duct Which cells release renin and why? A) JG cells via filtration osmolarity detection B) Macula densa cells via filtration osmolarity detection C) Podocytes due to blood pressure detection D) JG cells due to blood pressure detection E) Macula densa cells due to blood pressure detection Which cells release renin and why? A) JG cells via filtration osmolarity detection B) Macula densa cells via filtration osmolarity detection C) Podocytes due to blood pressure detection D) JG cells due to blood pressure detection E) Macula densa cells due to blood pressure detection Mr P has been prescribed a thiazide-like diuretic to help manage his chronic heart failure. Which of the following is a side effect of the diuretic? A) hypernatraemia B) Hyponatraemia C) Hyperkalaemia D) Hypocalcaemia E) Hypoglycaemia Mr P has been prescribed a thiazide-like diuretic to help manage his chronic heart failure. Which of the following is a side effect of the diuretic? A) hypernatraemia B) Hyponatraemia C) Hyperkalaemia D) Hypocalcaemia E) HypoglycaemiaMrs S presents unwell in A&E due to severe dehydration. She has been diagnosed with acute kidney injury. Her drug history includes verapamil, ramipril, paracetamol, bisoprolol, and salbutamol. Which medication is important to stop in AKI? A) Verapamil B) Ramipril C) Paracetamol D) Bisoprolol E) SalbutamolMrs S presents unwell in A&E due to severe dehydration. She has been diagnosed with acute kidney injury. Her drug history includes verapamil, ramipril, paracetamol, bisoprolol, and salbutamol. Which medication is important to stop in AKI? A) Verapamil - CCB B) Ramipril - ACE inhibitor C) Paracetamol D) Bisoprolol - B-blocker E) Salbutamol - SABA inhalerThanks for listening please fill in the feedback form!