GI-Associated Organs & Urinary Histology 2024 PDF

GI-Associated Organs & Urinary Histology Reis Chehardy & Jonathan Laredo [email protected] [email protected] Adapted from Slides by: Sarah Naids Chris Castelow Whitney Gulledge Sydney Stewart [email protected] [email protected] [email protected] [email protected] Lecture Objectives (GI-Associated Organs) Objective 1. Describe the spatial organization of the exocrine pancreas. Discuss the appearance and function of the cells constituting secretory units and ducts, including their secretory products. Summarize the enzymatic activities of those secretions and the regulation of their release. Objective 2. Describe the composition and function of bile. Objective 3. Describe the layers forming the wall of the gall bladder. Explain how the mucosa is specialized for its function of concentrating bile. Objective 4. Summarize the functions of the liver and the arrangement of cells into hepatic cords. Describe the location, appearance and function of hepatocytes, Ito cells, Kupffer cells, endothelial cells, and cholangiocytes in the liver. Be able to recognize a portal triad and identify its components. Objective 5. Describe the structure of liver sinusoids and explain the flow of blood within, entering, and exiting the liver. Objective 6. Explain the flow of bile through the biliary tree, starting with hepatocytes and ending with the hepatic duct. Objective 7. Explain the following ways of describing the functional organization of the liver: classic liver lobule, portal lobule, and liver acinus. Objective 8. Discuss the regenerative capacity of hepatocytes and describe the common disorders of the gall bladder and liver discussed in the lecture presentation. What are the functions of this organ? What are the functions of this organ? Concentrates & stores bile; pushes bile into duodenum for digestion Gallbladder Mucosa (highly-folded) ○ Simple columnar epithelium (junctional complexes) ○ Lamina propria w/ CT & immune cells ○ No muscularis mucosa or submucosa Muscularis externa w/ irregular arrangement Adventitia or serosa (depending on location) Functions: ○ Concentrates/stores bile: H2O moves from lumen → intercellular space via osmotic gradient & then high hydrostatic pressure → H2O into capillaries ○ Muscularis externa moves bile out into cystic duct during digestion Rokitansky-Aschoff sinuses: deep grooves of mucosa extending into muscularis externa due to abnormal overgrowth of epithelial cells ○ Can lead to gallstones and/or bacterial infections → cholecystitis Bile & Gallstones Bile ○ Mostly bile salts (cholesterol derivatives conjugated with taurine) Bile salts = bile acids ○ Emulsiﬁes fats → facilitates digestion ○ Helps regulate pH in duodenum ○ Elimination of Hemoglobin (as bilirubin) & excess cholesterol Gallstones – 2 types ○ 1. hardened cholesterol ○ 2. hardened bilirubin (pigment stones) ○ May necessitate removal of gallbladder Cholecystitis - due to gallstones or bacterial infection ○ Complications = cholangitis, liver abscess, carcinoma, peritonitis Which portion of the exocrine pancreas duct system is responsible for the addition of bicarb and water to the pancreatic ﬂuid? A. Centroacinar cells B. Intercalated ducts C. Intralobular ducts D. Interlobular ducts E. Duodenum Which portion of the exocrine pancreas duct system is responsible for the addition of bicarb and water to the pancreatic ﬂuid? A. Centroacinar cells B. Intercalated ducts C. Intralobular ducts D. Interlobular ducts E. Duodenum Exocrine Pancreas Serous glands divided into lobules ○ Cells arranged in acini; acinar cells → secrete zymogen granules into intercalated ducts ○ Tight junctions btwn cells Duct system: centroacinar cells (ﬂat) → intercalated ducts (squamous to short cuboidal; secrete HCO3-/H2O) → intralobular ducts (cuboidal to columnar) → interlobular ducts (columnar) → pancreatic duct → duodenum Exocrine Pancreas Secrete enzymes that break down proteins (trypsinogen, carboxypeptidase), carbohydrates (amylase), fats/lipids (lipases) & nucleic acids (deoxyribonucleases) Secretions controlled by duodenum enteroendocrine cells ○ Secretin, cholecystokinin (CCK): stimulate digestive enzyme release Pancreatic insuﬃciency results in maldigestion, esp. fats ○ can cause necrosis of acini Which of the following is not true regarding the functions of the liver? A. Produces bile B. Produces globulins, albumin, and clotting factors C. Inactivates hormones such as estrogen and thyroid hormone D. Stores copper and iron E. Helps to regulate blood glucose Which of the following is not true regarding the functions of the liver? A. Produces bile B. Produces globulins, albumin, and clotting factors C. Inactivates hormones such as estrogen and thyroid hormone D. Stores copper and iron E. Helps to regulate blood glucose Which of the following is not true regarding the functions of the liver? A. Produces bile B. Produces globulins, albumin, and clotting factors C. Inactivates hormones such as estrogen and thyroid hormone D. Stores copper and iron E. Helps to regulate blood glucose The liver does inactivate Estrogen (and Testosterone) but it ACTIVATES thyroid hormone (T4→ T3) What are the functions of the liver? What are the functions of the liver? 1. Produce bile 2. Synthesize plasma proteins (ie Albumin, clotting factors, lipoproteins) 3. Stores/regulates Cu, Fe, vitamins A, D, E, K, B12 4. Helps regulate blood glucose 5. Drug/toxin metabolism (via CYP450) Liver Functions Produces majority of plasma proteins ○ Ex. Albumin, globulins, lipoproteins, glycoproteins, clotting factors ○ Important for osmotic pressure, ﬂuid balance & transporting ions, minerals, fats Produces bile (1 L/day) Regulates vitamins (ADEK + B12), stores copper & iron Helps regulate carbohydrate metabolism & blood glucose levels Metabolism (CYPs) ○ Inactivates testosterone/estrogen ○ Activates T4 (thyroxine) → T3 (triiodothyronine; more active form) ○ Degrades drugs, toxins (alcohol) Which of the following cell types is responsible for ﬁbrosis of the liver? A. Kupffer cells B. Ito cells C. Hepatocytes D. Endothelial cells E. Hering cells Which of the following cell types is responsible for ﬁbrosis of the liver? A. Kupffer cells B. Ito cells C. Hepatocytes D. Endothelial cells E. Hering cells What else do all of these cells do? Which of the following cell types is responsible for ﬁbrosis of the liver? A. Kupffer cells: phagocytose pathogens and debris B. Ito cells: store vitamin A, make collagen C. Hepatocytes: hormone modiﬁcation, bile production, protein synthesis D. Endothelial cells: line blood vessels E. Hering cells: not real What else do all of these cells do? Cell Types Endothelial cells: line sinusoids Kupffer cells: specialized resident macrophages; reside within sinusoids Ito (stellate) cells: store vitamin A; can form collagen (ﬁbrosis); reside among hepatocytes Hepatocytes ○ Large, long-lived, polygonal, frequently binucleate; lots of Golgi & ER ○ Both endocrine & exocrine functions in same cell ○ Can regenerate (ex. partial liver transplants) ○ Plates/cords (2 basal surfaces; basal surface faces sinusoid capillaries) Space of Disse: perisinusoidal space btwn fenestrated endothelium & hepatocytes ○ Microvilli from hepatocytes → substance exchange btwn blood/hepatocytes Name the components of the portal triad: Name the components of the portal triad: 1. Bile duct 2. Portal vein 3. Hepatic artery B Label the components of the portal triad: A C B Label the components of the portal triad: A C A = bile duct B = hepatic artery C = portal vein Organization of Blood Flow Portal triad ○ Bile duct, portal vein, hepatic artery Portal canals: contain portal triad + surrounding CT, nerve, lymph Blood supply ○ Portal vein (75% of blood) Deoxygenated but lots of nutrients absorbed from GI tract ○ Hepatic artery (25%) Oxygenated w/ few nutrients Blood from both vessels enter via portal triad; mix in sinusoids & ﬂow towards the central vein Which is TRUE of bile canaliculi? A. Are bordered directly by endothelial cells B. Are part of the portal triad C. Are surrounded by hepatic sinusoids D. Converge into canals of Hering E. The produce that they carry is made by hepatic endothelial cells Which is TRUE of bile canaliculi? A. Are bordered directly by endothelial cells B. Are part of the portal triad C. Are surrounded by hepatic sinusoids D. Converge into canals of Hering E. The produce that they carry is made by hepatic endothelial cells Organization of Bile Flow Biliary tree ○ Bile made by hepatocytes; secreted into bile canaliculi ○ Canaliculi → canals of Hering → bile (interlobular) ducts → hepatic duct → bile exits liver Canaliculi: channels formed from grooves in adjacent hepatocytes (tight junctions) Canals of Hering (intrahepatic ductules): lined by hepatocytes, cholangiocytes & hepatic stem cells Bile duct: lined by cuboidal/columnar cholangiocytes & part of portal triad Bile ﬂows away from central vein (remember: blood ﬂows toward central vein) A classic liver lobule is the area that drains ________ from ________ towards a ________. A portal lobule is the area that drains _________ from ___________ towards a ________. A classic liver lobule is the area that drains blood from portal triads towards a central vein. A portal lobule is the area that drains bile from central canals towards a bile duct. Which zone is most susceptible to toxic PT substances and why? CV 3 2 1 Which zone is most susceptible to toxic PT substances and why? CV 3 2 1 ZONE 1 It is closest the hepatic artery in the portal triad Which zone is most susceptible to toxic PT substances and why? CV 3 2 1 ZONE 1 It is closest the hepatic artery in the portal triad Which zone is most susceptible to ischemia? Which zone is most susceptible to toxic PT substances and why? CV 3 2 1 ZONE 1 It is closest the hepatic artery in the portal triad Which zone is most susceptible to ischemia? Zone 3: furthest from oxygenated blood supply → centrolobular necrosis Organization Schemes Classic lobule: hexagonal prism w/ portal triads at each corner & central vein in middle (based on blood ﬂow toward CV) Portal lobule: triangular prism w/ central vein at each corner and portal triad in center (based on bile ﬂow toward PT) Liver acinus: oval shaped area btwn 2 adjacent portal triads and 2 adjacent central veins (based on perfusion & pathology) ○ Divided into 3 zones: zone 3 farthest from hepatic artery; most at-risk of ischemia Steatosis Cirrhosis Liver Pathology Jaundice: high bilirubin → yellowing of skin and sclera Hepatitis: liver inﬂammation from virus, trauma, or toxins; can be contagious Cirrhosis: CT and scar tissue replaces normal parenchyma; lead to loss of function & can be due to many causes (diseases, Rx, alcohol) – Quick think: what type of liver cells may be responsible for the ﬁbrosis? Steatosis: fat in hepatocytes (>10%) leading to impaired function; many causes (metabolic syndrome, alcoholism) Transplants: can be from living donor due to regenerative capabilities (common in pediatrics) Practice Q: GI Associated Organs (A) What is the organ (B) What is the name given to the structure at the black arrow? (C) Clinical correlate? A = gallbladder B = Rokitansky - Aschoff sinuses C = increased risk of bacterial entrapment + gallstones → association with cholecystitis Practice Q: GI Associated Organs (A) What is the organ (B) What is the name given to the structures at the arrows? A = liver B = bile canaliculi Practice Q: GI Associated Organs Where are hepatic stem cells located? A. Cords + Plates formed by hepatocytes B. Intercalated ducts C. Canal of Hering D. Sinusoids Practice Q: GI Associated Organs Where are hepatic stem cells located? A. Cords + Plates formed by hepatocytes B. Intercalated ducts C. Canal of Hering Explanation: D. Sinusoids A – cords/plates are made up of hepatocytes which border sinusoids – this is where exchange of substances occur between liver + blood B – intercalated ducts are located in the pancreas D – sinusoids house the macrophages of the liver (Kupffer cells) and are lined by endothelial cells that comprise the fenestrated vessels Lecture Objectives (Urinary) Theme of Urinary system: Structure determines Function 1. Summarize the overall architecture of the kidney, describing the appearance and major components of the cortical labyrinth, medullary rays, and medullary pyramids 2. Sketch the parts of a nephron and indicate the function of each part. Compare and contrast the appearance and function of proximal tubules, distal tubules, and collecting ducts 3. Describe the structure of the renal corpuscle, explain the process of glomerular ﬁltration and the function of the juxtaglomerular apparatus 4. Summarize the ﬂow of blood within the kidney Which of the following is FALSE regarding the functions of the kidney/urinary system? A. Major role in the excretion of nitrogenous waste B. Regulates many serum electrolytes & water, working in tandem w/ CV system to maintain BP C. Synthesizes renin & EPO D. Plays a negligible role in physiological Ca2+ balance E. Role in regulation of both serum & urinary osmolality Which of the following is FALSE regarding the functions of the kidney/urinary system? A. Major role in the excretion of nitrogenous waste B. Regulates many serum electrolytes & water, working in tandem w/ CV system to maintain BP C. Synthesizes renin & EPO D. Plays a negligible role in physiological Ca2+ balance E. Role in regulation of both serum & urinary osmolality Synthesizes 1-alpha-hydroxylase, which catalyzes last step in vitamin D metabolism → produces active (1,25-hydroxy vitD) form → stimulates Ca2+ reabsorption in gut Which of the following structures is located in the renal cortex? A. Vasa recta B. Thin limbs of loops of Henle C. Afferent arterioles D. Interlobar veins Which of the following structures is located in the renal cortex? A. Vasa recta B. Thin limbs of loops of Henle C. Afferent arterioles D. Interlobar veins Afferent arterioles are closely related to renal corpuscles (glomerulus + Bowman’s capsule), which are in the renal cortex All other answers are found in the medulla Which of the following statements concerning the structure of medullary rays is TRUE? A. Do not contain collecting tubules/ducts B. Contain proximal convoluted tubules C. Do not extend into the renal cortex D. Lie at the center of a renal lobule E. Contain thin limbs of the loops of Henle Which of the following statements concerning the structure of medullary rays is TRUE? A. Do not contain collecting tubules/ducts B. Contain proximal convoluted tubules C. Do not extend into the renal cortex D. Lie at the center of a renal lobule E. Contain thin limbs of the loops of Henle Medullary rays contain straight portions of tubules + CDs projecting from the medulla into the cortex A renal lobule spans half of one cortical labyrinth, across a medullary ray + half of the adjacent cortical labyrinth Kidney Cortex = labyrinth & medullary ray ○ Labyrinth = renal corpuscles (RC), PCTs & DCTs ○ Medullary ray = proximal & distal straight tubules & collecting ducts ○ Lobule: span from middle of 1 cortical labyrinth to middle of adj. (w/ medullary ray sandwiched in b/n Medulla = pyramids & renal column Nephron = basic functional unit of kidney Urinary system functions: ○ Filter blood; excrete waste in urine ○ Regulates ions, water, salt, electrolytes, osmolality, blood pressure (BP) ○ Synthesizes renin (BP) & erythropoietin (EPO; hematopoiesis) ○ Produces active form of vitamin D (1,25-OH vitD) → involved in Ca2+ homeostasis Cortex Medulla Corticomedullary junction (CMJ) Nephron Nephron ○ Renal corpuscle (RC) = glomerulus + Bowman’s capsule ○ Proximal convoluted tubule (PCT) ○ Proximal straight tubule ○ Loop of Henle ○ Distal straight tubule ○ Distal convoluted tubule (DCT) Collecting tubule/duct ○ Different embryological origin Uriniferous tubule = nephron + connecting tubule/duct Name the regions indicated by the letters A & B: A: B: A B Name the regions indicated by the letters A & B: A: Urinary pole B: Vascular pole A B Name the regions indicated by the letters A & B: A: Urinary pole C B: Vascular pole A What is the primary function of the cells indicated by the letter C ? B Name the regions indicated by the letters A & B: A: Urinary pole C B: Vascular pole A What is the primary function of the cells indicated by the letter C ? Macula densa (MD); monitor Na+ concentration B in distal tubule & stimulate juxtaglomerular cells to release renin (when Na+ low) Renal Corpuscle Glomerulus = fenestrated tuft of capillaries; blood ﬁlters out of here Bowman’s capsule = collects ﬁltered blood; double membrane ○ Inner visceral (formed by podocytes w/n glomerulus) ○ Outer parietal (simple squamous epithelium) Urinary space = b/n visceral & parietal layers of Bowman’s capsule Vascular pole = blood enters via afferent arteriole & leaves via efferent arteriole Urinary pole = ﬁltrate carried to rest of nephron Which of the following is TRUE regarding the structure of the glomerular basement membrane (GBM) & adjacent ﬁltration barriers? A. Lamina densa is the primary charge barrier (due to neg. charge of heparin sulfate moieties) B. Pedicel ﬁltration slits play an important role in maintaining glomerular ECM functions C. Intraglomerular mesangial cells help to regulate size of ﬁltered molecules D. Lamina rara is the primary barrier in preventing ﬁltration of large anionic proteins (ex. albumin) Which of the following is TRUE regarding the structure of the glomerular basement membrane (GBM) & adjacent ﬁltration barriers? A. Lamina densa is the primary charge barrier (due to neg. charge of heparin sulfate moieties) B. Pedicel ﬁltration slits play an important role in maintaining glomerular ECM functions C. Intraglomerular mesangial cells help to regulate size of ﬁltered molecules D. Lamina rara is the primary barrier in preventing ﬁltration of large anionic proteins (ex. albumin) Name the 3 ﬁltration barriers that a (ﬁlterable) molecule passes through as it travels from the glomerulus to the urinary space: 1. 2. 3. Name the 3 ﬁltration barriers that a (ﬁlterable) molecule passes through as it travels from the glomerulus to the urinary space: 1. Endothelium of fenestrated capillaries 2. Glomerular basement membrane (GBM) 3. Podocyte pedicels Glomerulus Loops of fenestrated capillaries Podocytes: cells w/ large foot processes that branch further (secondary processes; aka pedicels) ○ Basement membranes of endothelial cells + podocytes fuse → glomerular basement membrane (GBM) Intraglomerular mesangial cells ○ Secrete ECM molecules; maintenance function ○ Phagocytosis Prevent “clogging” of GBM Filtration Filtrate must pass through: (1) fenestrated capillaries, (2) glomerular basement membrane & (3) ﬁltration slits of podocyte pedicels to reach urinary space ○ Fenestrations are large but prevent RBCs from entering ﬁltrate ○ Glomerular basement membrane (GBM) Lamina rara externa & interna: ﬁxed negative charges (heparin sulfate); charge barrier Lamina densa: type IV collagen; size barrier ○ Podocytes Pedicel ﬁltration slits: selective size ﬁlter The vast majority of ﬂuid ﬁltered by the glomeruli is reabsorbed primarily by which portion of the functional nephron? A. Proximal convoluted tubule (PCT) B. Loop of Henle (LoH) C. Distal convoluted tubule (DCT) D. Collecting tubules/ducts The vast majority of ﬂuid ﬁltered by the glomeruli is reabsorbed primarily by which portion of the functional nephron? A. Proximal convoluted tubule (PCT) B. Loop of Henle (LoH) C. Distal convoluted tubule (DCT) D. Collecting tubules/ducts Which of the following statements is most correct regarding the proximal convoluted tubule (PCT)? A. Recovers a minimal amount of ﬂuid compared to more distal portions of the nephron B. Lined by stratiﬁed cuboidal epithelium C. Water is reabsorbed from the ultraﬁltrate mainly via a paracellular mechanism D. Reabsorbs almost all ﬁltered glucose & AAs E. Largely devoid of microvilli brush border Which of the following statements is most correct regarding the proximal convoluted tubule (PCT)? A. Recovers a minimal amount of ﬂuid compared to more distal portions of the nephron B. Lined by stratiﬁed cuboidal epithelium C. Water is reabsorbed from the ultraﬁltrate mainly via a paracellular mechanism D. Reabsorbs almost all ﬁltered glucose & AAs E. Largely devoid of microvilli brush border FYI Clinical Correlate: *SGLT → sodium-glucose linked transporter Proximal Tubules Important class of drugs for Tx of type 2 diabetes (T2DM) = SGLT2 inhibitors (“-gliﬂozins); inhibit glucose reabsorption → lower blood sugar Proximal convoluted tubule (PCT) ○ Recovers 2/3 of ﬂuid in ultraﬁltrate ○ Large, pyramidal-shaped cells w/ microvilli (brush border), elongated mitochondria (basal striations) & infolded basal/lateral membranes ○ Many ion channels & transporters Na+ reabsorbed via Na+/K+ ATPase Water via aquaporin (AQP) channels Polypeptides/proteins via endocytosis Glucose (~100% reabsorbed) via SGLT*; AAs (~98% reabsorbed) Proximal straight tubule = thick descending limb of Loop of Henle ○ Still active like PCT so brush border and mitochondria but a bit less active ○ Cells slightly more cuboidal ○ Microvilli shorter/less numerous; fewer mitochondria & membrane infolding Proximal Tubules What type of stain is useful to stain (in PCT & proximal straight tubules)? And why? What type of stain is useful to stain (in PCT & proximal straight tubules)? And why? Periodic acid-Schiff (PAS); binds to carbohydrates; bright pink color Reveals brush borders and basement membranes Which of the following statement(s) regarding the Loop of Henle (LoH) is true? More than one answer may be correct A. Thick descending limb is completely devoid of brush border B. Simple squamous epithelium predominate in the thin ascending limb C. Thin ascending limb is remarkably permeable to water, leading to signiﬁcant conc. of luminal ﬂuid D. Thick ascending limb is impermeable to water & actively reabsorbs luminal Na+ (along w/ other electrolytes) E. Thick limbs are characterized by stratiﬁed cuboidal epithelium Which of the following statement(s) regarding the Loop of Henle (LoH) is true? More than one answer may be correct A. Thick descending limb is completely devoid of brush border B. Simple squamous epithelium predominate in the thin ascending limb C. Thin ascending limb is remarkably permeable to water, leading to signiﬁcant conc. of luminal ﬂuid D. Thick ascending limb is impermeable to water & actively reabsorbs luminal Na+ (along w/ other electrolytes) E. Thick limbs are characterized by stratiﬁed cuboidal epithelium Which of the following statement(s) regarding the Loop of Henle (LoH) is true? More than one answer may be correct A. Thick descending limb is completely devoid of brush border B. Simple squamous epithelium predominate in the thin ascending limb C. Thin ascending limb is remarkably permeable to water, leading to signiﬁcant conc. of luminal ﬂuid D. Thick ascending limb is impermeable to water & actively reabsorbs luminal Na+ (along w/ other electrolytes) E. Thick limbs are characterized by stratiﬁed cuboidal epithelium What is wrong w/ the other answers? Which of the following statement(s) regarding the Loop of Henle (LoH) is true? More than one answer may be correct Same as proximal straight tubule A. Thick descending limb is completely devoid of brush border (some brush border) B. Simple squamous epithelium predominate in the thin ascending limb C. Thin ascending limb is remarkably permeable to water, leading to signiﬁcant conc. of luminal ﬂuid Thin descending limb D. Thick ascending limb is impermeable to water & actively reabsorbs luminal Na+ (along w/ other electrolytes) E. Thick limbs are characterized by stratiﬁed cuboidal epithelium Simple cuboidal epithelium What is wrong w/ the other answers? Loop of Henle (LoH) 4 parts: Thick Thin ○ Thick descending limb (proximal straight tubule) ○ Thin descending limb High perm. to water; water leaves → very high osmolarity in interstitium of medulla ○ Thin ascending limb Imperm. to water; Na+ reabsorbed ○ Thick ascending limb (distal straight tubule) Lined by low cuboidal cells (mitochondria but no brush border) Imperm. to water; Na+ reabsorbed via Na+/K+ ATPase K+, Ca2+ & Cl- reabsorbed Simple squamous epithelium in thin limbs & simple cuboidal in thick limbs Which are distal (D) vs. proximal (P) straight tubules? How can you tell? P D P P D Which are distal (D) D vs. proximal (P) P straight tubules? How can you tell? D P = PAS-pos. staining P D of residual brush border inside lumen Which of the following is TRUE about the juxtaglomerular apparatus (JGA)? A. It is composed of the juxtaglomerular cells, macula densa, and specialized smooth muscle cells in the afferent and efferent arteriole B. It helps to increase sodium and water reabsorption with the sodium concentration in the distal convoluted tubule is elevated C. It regulates the production of a substance that causes vasoconstriction D. It increases production of angiotensin I from the afferent and efferent arteriole when blood arteriole pressure is low Which of the following is TRUE about the juxtaglomerular apparatus (JGA)? A. It is composed of the juxtaglomerular cells, macula densa, and specialized smooth muscle cells in the afferent and efferent arteriole B. It helps to increase sodium and water reabsorption with the sodium concentration in the distal convoluted tubule is elevated C. It regulates the production of a substance that causes vasoconstriction D. It increases production of angiotensin I from the afferent and efferent arteriole when blood arteriole pressure is low Juxtaglomerular Apparatus (JGA) Macula densa (MD) ○ Found in distal tubule; closely-packed cells w/ overlapping nuclei ○ Monitor Na+ conc. → if low, stimulate juxtaglomerular cells Juxtaglomerular cells ○ Specialized smooth muscle cells on afferent & efferent arterioles; secrete renin when stimulated by MD ○ Also responds to low afferent arteriole pressure Renin converts angiotensinogen (made in liver) to angiotensin I Angiotensin I converted to angiotensin II in lung via angiotensin-converting enzyme (ACE) → vasoconstriction Release of aldosterone (from adrenal cortex) → increases Na+ reabsorption → raises BV & BP Extraglomerular mesangial cells ○ Located around vascular pole; phagocytic Renin-Angiotensin Aldosterone System (RAAS) Juxtaglomerular Apparatus (JGA) Which of the following differentiates the distal convoluted tubule from the proximal convoluted tubule? A. The ability to reabsorb electrolytes B. The presence of a brush border C. Infolding of basal and lateral membranes D. The presence of elongated mitochondria Which of the following differentiates the distal convoluted tubule from the proximal convoluted tubule? A. The ability to reabsorb electrolytes B. The presence of a brush border C. Infolding of basal and lateral membranes D. The presence of elongated mitochondria Distal Convoluted Tubule (DCT) Continued absorption of electrolytes & pH adjustment Smaller cells compared to those in PCT ○ Few, irregular microvilli; no brush border ○ Many elongated mitochondria w/ infolding of basal/lateral membranes Transport regulated by aldosterone You are on a 3 day camping trip and after the ﬁrst night you lose your supplies to a hungry bear. After 24 hours w/o food or water your urine is extremely concentrated, mediated in part by an important hormone. This hormone acts via binding its receptor & promoting water absorption primarily in which portion of the Uriniferous Tubule? A. Loop of Henle B. Distal convoluted tubule (DCT) C. Collecting tubules/ducts D. Proximal convoluted tubule (PCT) E. Glomerulus You are on a 3 day camping trip and after the ﬁrst night you lose your supplies to a hungry bear. After 24 hours w/o food or water your urine is extremely concentrated, mediated in part by an important hormone. This hormone acts via binding its receptor & promoting water absorption primarily in which portion of the nephron? A. Loop of Henle B. Distal convoluted tubule (DCT) Hormone = antidiuretic hormone (ADH) C. Collecting tubules/ducts Binds receptor & stimulates AQP translocation to luminal D. Proximal convoluted tubule (PCT) membrane → water reabsorption in collecting ducts E. Glomerulus Which two hormones have their primary action in cuboidal cells of the collecting ducts? Which two hormones have their primary action in cuboidal cells of the collecting ducts? Aldosterone (Na+ reabsorption; H+/K+ excretion) ADH (water reabsorption) Collecting Tubules/Ducts Lined by well-demarcated cuboidal cells; lightly-stained Na+ reabsorption via aldosterone ○ Coupled to K+ and H+ excretion Water reabsorption via antidiuretic hormone (ADH) ○ ADH → translocation of AQPs to luminal surface → water reabsorption CD CD CD CD CD CD A Name the renal vessels indicated by the letters A, B & C: B A: B: C C: A Name the renal vessels indicated by the letters A, B & C: B A: interlobular vessels B: arcuate vessels C C: vasa recta Cortex A Name the renal vessels indicated by the letters A, B & C: B A: interlobular vessels B: arcuate vessels C C: vasa recta Medulla Blood in the cortical glomeruli (those which lie primarily in the cortex), after passing through the glomerulus & exiting via the efferent arteriole, will pass where next? A. Arteriolae rectae B. Peritubular capillary plexus C. Afferent arteriole D. Interlobular arteries E. Proximal tubule Blood in the cortical glomeruli (those which lie primarily in the cortex), after passing through the glomerulus & exiting via the efferent arteriole, will pass where next? A. Arteriolae rectae B. Peritubular capillary plexus C. Afferent arteriole D. Interlobular arteries E. Proximal tubule Red = arterial; blue = venous; purple = mixed; yellow = biliary; green = lymphatic BLOOD, LYMPH & BILE FLOW Renal blood ﬂow: Renal artery → interlobar arteries → arcuate arteries → interlobular arteries → afferent arterioles → glomerulus → efferent arterioles → peritubular capillaries (if glomeruli are in outer areas of cortex) or vasa recta (if glomeruli are near medulla) Interlobular veins → arcuate veins → interlobar veins → renal vein → IVC Red = arterial; blue = venous; purple = mixed; yellow = biliary; green = lymphatic BLOOD, LYMPH & BILE FLOW Renal blood ﬂow: Renal artery → interlobar arteries → arcuate arteries → interlobular arteries → afferent arterioles → glomerulus → efferent arterioles → peritubular capillaries (if glomeruli are in outer areas of cortex) or vasa recta (if glomeruli are near medulla) Interlobular veins → arcuate veins → interlobar veins → renal vein → IVC Renal Blood Flow Arterial supply ○ Renal artery → interlobar arteries (through medulla up to CMJ) → arcuate arteries (run along CMJ) → interlobular arteries (through cortex) → afferent arterioles → glomerular capillaries → efferent arterioles Outer glomeruli in cortex: efferent arterioles → peritubular capillaries Glomeruli nea medulla: efferent arterioles → vasa recta Venous return ○ Interlobular veins → arcuate veins → interlobar vein → renal vein Excretory Passages Ureters → bladder → urethra ○ Storage (bladder) & outﬂow tracts for urine produced by kidneys Predominantly lined by transitional epithelium Distended Relaxed Hi-Yield for practical! Questions? Red = arterial; blue = venous; purple = mixed; yellow = biliary; green = lymphatic BLOOD, LYMPH & BILE FLOW Renal blood ﬂow: Renal artery → interlobar arteries → arcuate arteries → interlobular arteries → afferent arterioles → glomerulus → efferent arterioles → peritubular capillaries (if glomeruli are in outer areas of cortex) or vasa recta (if glomeruli are near medulla) Interlobular veins → arcuate veins → interlobar veins → renal vein → IVC Liver blood ﬂow (classic liver lobule): Portal triad (bile duct, portal vein, hepatic artery) → sinusoids → central vein Liver bile ﬂow (portal lobule): Bile canaliculi (b/n hepatocytes) → canals of Hering → interlobular bile ducts → hepatic ducts Lymph node lymphatic ﬂow: Afferent lymphatic vessel → subcapsular/cortical sinus → trabecular sinus → medullary sinuses → efferent lymphatic vessel Pancreas serous secretions ﬂow: Centroacinar cells → intercalated ducts → intralobular ducts → interlobular ducts → duodenum http://www.siumed.edu/~dking2/erg/index.htm Great site for practice Histo questions (unfortunately only has “self-assessment” sections for endocrine, repro & GI) Practice Questions A 30-year-old man comes to his physician’s oﬃce because he has had a persistent blood-tinged cough for several months. Hx reveals that the patient has had episodes of dark red urine. Vital signs are normal. Laboratory tests reveal anemia. A urinalysis is positive for RBCs. What is the most likely cause of this pt’s symptoms? A. Selective immune complex deposition in the alveolar epithelium B. AutoAbs to type IV collagen C. Kidney stones D. Mutation in type IV collagen E. Destruction of intraglomerular mesangial cells A 30-year-old man comes to his physician’s oﬃce because he has had a persistent blood-tinged cough for several months. Hx reveals that the patient has had episodes of dark red urine. Vital signs are normal. Laboratory tests reveal anemia. A urinalysis is positive for RBCs. What is the most likely cause of this pt’s symptoms? A. Selective immune complex deposition in the alveolar epithelium B. AutoAbs to type IV collagen C. Kidney stones D. Mutation in type IV collagen E. Destruction of intraglomerular mesangial cells A 30-year-old man comes to his physician’s oﬃce because he has had a persistent blood-tinged cough for several months. Hx reveals that the patient has had episodes of dark red urine. Vital signs are normal. Laboratory tests reveal anemia. A urinalysis is positive for RBCs. What is the most likely cause of this pt’s symptoms? A. Selective immune complex deposition in the alveolar epithelium B. AutoAbs to type IV collagen C. Kidney stones D. Mutation in type IV collagen What is this syndrome called? E. Destruction of intraglomerular mesangial cells A 30-year-old man comes to his physician’s oﬃce because he has had a persistent blood-tinged cough for several months. Hx reveals that the patient has had episodes of dark red urine. Vital signs are normal. Laboratory tests reveal anemia. A urinalysis is positive for RBCs. What is the most likely cause of this pt’s symptoms? A. Selective immune complex deposition in the alveolar epithelium B. AutoAbs to type IV collagen C. Kidney stones D. Mutation in type IV collagen What is this syndrome called? E. Destruction of intraglomerular mesangial cells Goodpasture syndrome; autoAbs to type IV collagen (found in both GBM of kidney & BM of pulmonary alveoli) IHC staining on the tissue section shown to the right is speciﬁc for CD3+, a surface marker for T cells (“positive” CD3+ cells are brown). What is the proper C B label for the location designated by the letter A? A D IHC staining on the tissue section shown to the right is speciﬁc for CD3+, a surface marker for T cells (“positive” CD3+ cells are brown). What is the proper C B label for the location designated by the letter A? A A: Paracortex D IHC staining on the tissue section shown to the right is speciﬁc for CD3+, a surface marker for T cells (“positive” CD3+ cells are brown). What is the proper C B label for the location designated by the letter A? A A: Paracortex IHC staining for surface markers of what cell type would stain positive at B? D IHC staining on the tissue section shown to the right is speciﬁc for CD3+, a surface marker for T cells (“positive” CD3+ cells are brown). What is the proper C B label for the location designated by the letter A? A A: Paracortex IHC staining for surface markers of what cell type would stain positive at B? B cells (germinal center) D A patient who was given penicillin had an adverse reaction to the antibiotic. The reaction resulted from degranulation of mast cells via IgE receptors on their cell membranes. Which of the following cells produced the IgE that elicited the degranulation event? A. T memory cells B. Plasma cells C. Memory B cells D. T helper cells E. Cytotoxic T cells A patient who was given penicillin had an adverse reaction to the antibiotic. The reaction resulted from degranulation of mast cells via IgE receptors on their cell membranes. Which of the following cells produced the IgE that elicited the degranulation event? A. T memory cells B. Plasma cells C. Memory B cells D. T helper cells E. Cytotoxic T cells A patient complains to her physician about sudden weight loss, loss of appetite, weakness & back pain. Because the patient’s sclera and skin have a yellowish pallor, the doctor suspects: A. Type II diabetes B. Cholecystitis C. Gallstones D. Viral hepatitis E. Pancreatic insuﬃciency A patient complains to her physician about sudden weight loss, loss of appetite, weakness & back pain. Because the patient’s sclera and skin have a yellowish pallor, the doctor suspects: Jaundice → think liver pathology! A. Type II diabetes B. Cholecystitis C. Gallstones D. Viral hepatitis E. Pancreatic insuﬃciency Along most of the GI tract (except for the oral cavity and lower anal canal), the basal boundary of the mucosa is marked by: A. Thick layer of striated smooth muscle B. Thin (& often inconspicuous) smooth muscle layer--muscularis mucosa C. Myenteric plexus D. Fibrous CT of serosa or adventitia E. Mesothelium Along most of the GI tract (except for the oral cavity and lower anal canal), the basal boundary of the mucosa is marked by: A. Thick layer of striated smooth muscle B. Thin (& often inconspicuous) smooth muscle layer--muscularis mucosa C. Myenteric plexus D. Fibrous CT of serosa or adventitia E. Mesothelium In most regions of the GI tract (exceptions are oral cavity and stomach), smooth muscle ﬁbers of the muscularis externa are arranged into: A. Inner circular and outer longitudinal layers B. Outer circular and inner longitudinal layers C. Circular and longitudinal layers whose relative position varies from region to region D. Interwoven meshwork of circular and longitudinal muscle ﬁbers E. Bundles aligned along three mutually-perpendicular directions In most regions of the GI tract (exceptions are oral cavity and stomach), smooth muscle ﬁbers of the muscularis externa are arranged into: A. Inner circular and outer longitudinal layers B. Outer circular and inner longitudinal layers C. Circular and longitudinal layers whose relative position varies from region to region D. Interwoven meshwork of circular and longitudinal muscle ﬁbers E. Bundles aligned along three mutually-perpendicular directions SUPPLEMENTAL E = efferent arteriole EM showing transition from parietal layer of Bowman’s CL = capillary loops capsule to PCT (note well-deﬁned brush border) SUPPLEMENTAL PATHOLOGY SLIDE (Not on Exam) Diabetic nephropathy (DN) = chronic damage/loss of kidney function as a result of long-standing poorly controlled blood glucose in diabetes mellitus Most common cause of end-stage renal disease (ESRD) Characterized histologically via by presence of nodular glomerulosclerosis “Glomerulo-” preﬁx = pathology occurs in glomerulus Nodular foci; PAS-positive (sometimes called Kimmelstiel-Wilson (KW) nodules) Nodular glomerulosclerosis w/ both H&E (A) and PAS (B) staining, consistent w/ KW nodules of DN Other renal histology ﬁndings seen w/ DN (IFTA; hyaline arteriolosclerosis) SUPPLEMENTAL Nodulous hepatocellular carcinoma of the liver Notice how normal parenchymal liver tissue is obscured by neoplastic cells FYI Clinical Correlate: Another Important class of drugs = diuretics Commonly-used for Tx of hypertension (HTN) Inhib. Na+ reabsorption → Na+ & water excreted (“diuresis”); counteracts/lessens hypertensive load → reduces BV/BP LoH DCT “Loop” diuretics → work in thick ascending limb “Thiazide” diuretics → work in DCT of LoH

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