Urine Luck! Renal slides by Dan Cushman Donations accepted and strongly encouraged Lobe Interlobar artery Cortex Medulla Renal artery divides into anterior and posterior branches. Renal vein Renal pelvis Ureter Kidney parasite Parasitium nephrotium (Just kidding, of course, it’s a nephron) Vessels Name the arteries of the kidney from largest to smallest 1. Renal Artery 2. Interlobar artery 3. Arcuate artery 4. Interlobular artery 5. Afferent arteriole 6. Efferent arteriole Kidney vessels Renal corpuscles Cortex Interlobular vessels Arcuate vessels Medulla Interlobar vessels X10 Nephron segments Proximal convoluted tubule Proximal straight tubule Descending limb of Henle Thin Ascending limb of Henle Thick Ascending limb of Henle Distal convoluted tubule Collecting duct Cortex Medulla Renal corpuscle (Layer) Efferent arteriole Afferent arteriole Visceral layer Urinary pole (Layer) Parietal layer What is the best word in nephrology? Corpuscle What is the best structure in There really is not an nephrology? answer to this question. It’s more of a personal reflection question with no objective answer. “Best” is hard to quantify. Filtration apparatus Endothelial cell nucleus Podocyte Primary process Secondary process (pedicel) Where are large anions repelled? Glomerular Capillary basement lumen (Glomerulus membrane lumen) What is this? Can’t you read? Mesangial cells Visceral layer – What are the functions of mesangial cells? Podocyte Efferent a. Phagocytic – clean the basement membrane, arteriole ex. Remove immune complexes from the membrane. b. Support – podocytes. c. They are contractile- can regulate glomerular lumen. d. Secretory – Interleukin-1 and platelet-derived growth factor. These respond to glomerular Afferent injury. arteriole Parietal layer So… tell me about the juxtaglomerular cells. Maculamuscle cells of the afferent arteriole. a. Smooth Theydensa are innervated by sympathetic neurons Distal and secrete renin into the blood. convoluted tubule Afferent arteriole Juxtaglomerular cells Which is which? (Brush Border) Proximal Tubule Distal Tubule Which is which? Full Bladder Empty Bladder Which portion What is its main turns into a kidney? signaler? Neural tube Paraxial Mesoderm Gut Intermediate Mesoderm Order these three chronologically Which one turns Mesonephric kidney Pronephric kidney into your kidney? Metanephric kidney Which one turns into the ductus deferens? Metanephros What transcription Mesonephros tubules factor do I create? Hindgut Mesonephric duct WT1 Cloaca Ureteric bud Which induces what other factor? Metanephric Mesoderm (blastema) GDNF Name the defect Pelvic kidney Bifid ureter Horseshoe kidney Where’s the bladder? Here Where’s the love? All around us Normals Property Value Renal blood flow (mL/min) 1200 Renal plasma flow (mL/min) 660 GFR (mL/min) 125 Filtration fraction 0.20 – 0.25 Total body water (% of total body weight) 60% ICFV (% of total body water) 60-67% ECFV (% of total body water) 33-40% Plasma volume (% of total body weight) 4% Urine osmolarity (mosm/L) 500-800 Plasma osmolarity (mosm/L) 285 Substances Substance Importance PAH CPAH = ERPF Inulin Cinulin = GFR Creatinine Ccreatinine = GFR (overestimate) Match each to a line Filtered Excreted Secreted Will the hypertonic gradient in the medullary interstitium ↑ or ↓? Event Increase or decrease Solute diuresis ↓ Reduced blood flow through vasa recta ↑ Inhibition of Na, K, 2 Cl cotransporter ↓ Washout of urea ↓ Increased number of JM nephrons ↑ Renal disease ↓ Match transporters with location Thick ascending loop of Henle Na/HCO3 antiport Thin ascending loop of Henle Na/glucose symport Descending loop of Henle Na/H antiport Proximal Tubule Na/K/2 Cl symport How do V2 receptors function? They are localized in the basolateral What causes ADH release (6)? membranes of principal cells. Activation of V2 receptors elevates •Increase in plasma osmolarity (1-2% cyclic AMP in these cells, which leads to threshold) insertion of water-permeable channels •Reduction in circulating blood volume (>10%) (AQP2) into the lumenal membrane. and blood pressure •Angiotensin II •Stress (physical or emotional), pain •Nausea •Standing upright (→orthostatic antidiuresis) What percentage is reabsorbed in each section? 65% 65% Na H2O Coupled with which anions? Cl- (50% of its filtered amount) and HCO3- (90%) 25% Na 15% H2O Cl- (33% of its filtered amount) Coupled with which anions? Where is the lower O2 content? The cortex The medulla Rearrange these urea transporters to make a face. Order these in terms of reaction speed Baroreceptor reflex Fast Renal control of body NaCl Medium Angiotensin II Slow Renal Regulation: High, Intermediate, or Low? Intermediate Low [Cr]P ↑ as nephrons are lost HCO3Creatinine Low Urea High Na+ High Water Intermediate Ca2+ Match the lines Which will have the greatest osmolarity? Saline Saline Glucose or water Alcohol ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ Each caused by what? ↑ perfusion pressure, NE, (ATII) ↑/↓ ↑/↓ ↑/↓ ATII ↑/↓ ↑/↓ ↑/↓ ATII ↑/↓ ↑/↓ ↑/↓ What will increase FENa? Constriction orDilation Dilation of efferent arteriole Increase orDecrease Decrease activation of RAA system Increase or Decrease Increase secretion of natriuretic hormones ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ Aldosterone Direct stimulants (2): MostActs importantly, on (2): what happens to PrincipalFENa? cells do what (4): ↑ [K+]plasma, ATII Late distal tubule, collecting ducts - Increased Na+ permeability of lumenal membrane - Increased K+ permeability of lumenal membrane - Increased lumenal Na+/H+ exchange - Increase in activity and number of basolateral Na+,K+-ATPase pumps It decreases! Intercalated cells do what (1): - Increased lumenal H+-ATPase activity ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ Choose: Osmoregulation or Volume Regulation? Osmoregulation Senses plasma osmolality Osmoregulation Regulates ADH, thirst Volume Regulation Affects urine Na excretion Volume Regulation Takes days to occur Volume Regulation Edema is a physical sign Volume Regulation ADH, ANP, RAA system Volume Regulation (Sensor) Baroreceptors ↑ Sympathetics (hormone) ↑ Renin ↑ ATII Name the three substances that increase the Na/K ATPase activity 1 1 2 3 2 2 Which side represents a reaction to a state of low K+? What exchange occurs in principal cells? Na+ in, K+ and H+ out What exchange occurs in intercalated cells? K+ in, H+ out Effect on K+ excretion Property Inc/Dec Low K+ diet ↓ High K+ permeability of lum. membrane ↑ Decreased fluid flow through lumen ↓ Increased intralumenal negativity ↑ High Na+ diet ↑ Metabolic alkalosis ↑ Aldosterone + high fluid flow rates ↑↑ Effect on HCO3- Reabsorption Property Inc/Dec Decreased filtered load of HCO3- ↓ Increased arterial pCO2 ↑ Low angiotensin II ↓ Respiratory acidosis ↑ Decreased ECFV ↑ ↑ Aldosterone ↑ Effect on Ammonium Excretion Property Inc/Dec K+ elevation ↓ Acute respiratory acidosis ↑ Metabolic acidosis ↑ Acidic urinary pH ↑ Effect on Titratable Acidity of Urine Property Inc/Dec High pH ↓ Increased filtered load of phosphate ↑ Decreased PTH ↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ ↑/↓ Hyper- or Hypokalemia? Property Value Increased K+ intake Hyperkalemia Increased GI loss Hypokalemia Excessive insulin administration Hypokalemia Renal failure Hyperkalemia Untreated diabetes mellitus Hyperkalemia Treatment with thiazides/L-A diuretics Hypokalemia Primary hyperaldosterism Hypokalemia This patient is treated with ACE inhibitors Hypokalemia Treated with calcium chloride infusion Hyperkalemia Treated with adrenergic agonist Hyperkalemia Name the drugs B (3 drugs) A Identify the following Metabolic alkalosis Chronic respiratory acidosis Chronic respiratory alkalosis Acute respiratory acidosis Effect (Plasma) [Na] pH [Na] [K] [Ca] ↓ ↑/↓ ↑ ↑/↓ [Mg] Pi HCO3 ADH ↑/↓ ↑/↓ Aldost Met Ac Met Alk ↓ ↑/↓ ↓ ↑/↓ pH [K] ↑ ↑/↓ [Ca] ↑ ↑/↓ ↓ ↑/↓ ↑ ↑/↓ ↓ ↑/↓ Cause (high) [Mg] ↓ ↑/↓ Pi ↑/↓ ↓ HCO3 ADH Aldost ↑ ↑/↓ ↑ ↑/↓ Met Ac ↓ ↑/↓ Met Alk ↑/↓ ↑ Resp Ac ↓ ↑/↓ Resp Alk ↑/↓ ↑ ↑ ↑/↓ ↑ ↑/↓ ↑/↓ ↓ ↑/↓ ↓ ↓ ↑/↓ ↑ ↑/↓ ↓ ↑/↓ ↑/↓ ↓ ↑ ↑/↓ ↑ ↑/↓ ↓ ↑/↓ ↑/↓ ↓ ↑/↓ ↑ ↑ ↑/↓ PTH ANP ↓ ↑/↓ ↑ ↑/↓ ↓ ↑/↓ ↓ ↑/↓ ↓ ↑/↓ ↑ ↑/↓ And now… Kay’s slides Everything wrong was her fault Is Na+ reabsorbed or secreted in the proximal convoluted tubule? Reabsorbed! Actively reabsorbed. Known Is Na+ reabsorbed or secreted as the first cortical in the 2/3 diluting of the distal segment. convoluted tubule? By what mechanism is it reabsorbed? By a wide variety of Na+linked lumenal transporters and solvent drag. And finally, whatand about Reabsorption occurs is the late distal convoluted tubule and the stimulated by aldosterone. collecting duct? What diuretics work here? K+-sparing diuretics. X What diuretics work here? Thiazides. What diuretics work here? Is Na+ reabsorbed or secreted in the thick ascending limb of the loop of Henle? Reabsorbed via the Na+, K+, 2Clco-transporter. Known as the Neither! For the most part, the medullary diluting segment. + reabsorbed Is Na or secreted thin descending limb only in the thinwater. descending limb of reabsorbs the loop of Henle? Is Na+ reabsorbed or secreted in the thin ascending limb of thereabsorbed. loop of Henle? Passively Carbonic Anhydrase Inhibitors What diuretics work here? Loop-acting diuretics. In the proximal tubule, are the following secreted or reabsorbed? Water: Reabsorbed % of filtered:65% Urea: Reabsorbed (50%) K+: Reabsorbed (67%) Ca2+: Reabsorbed (67%) Pi: Reabsorbed (majority) Mg2+: No movement What is reabsorbed in the thin descending limb of the loop of Henle? Mainly just water! In the thick ascending limb of the loop of Henle, what is reabsorbed? Na+, K+, Cl-, Ca2+, Mg2+ In the thin ascending limb of the loop of Henle, what is reabsorbed? Na+, Cl- What is secreted? Urea (60%-110%) What happens in the first 2/3 of the distal convoluted tubule? •ALWAYS impermeable to water •Reabsorbs Na+ •Called the cortical diluting segment What happens in the last 1/3 of the distal convoluted tubule? •Absorbs water ONLY when ADH is present •Can reabsorb Na+ against a large electrochemical gradient Distal tubule in general also reabsorbs Ca2+ and a little bit of Mg2+ What about K+? K is actively reabsorbed by intercalated cells & passively secreted by principal cells Finally, we come to the collecting duct: Na+: Reabsorbed Urea: Reabsorbed (40% to 70%) (only in the medullary region) K+: Reabsorbed or secreted Water: Reabsorbed (only w/ ADH) Mg2+: No movement Pi: No movement Ca2+: No movement