RENAL DISEASE: Overview of Kidney Structure and Function Pathophysiology of Disease: Chapter 16 (382-404)

1. RENAL DISEASE:Overview of Kidney Structure and FunctionPathophysiology of Disease: Chapter 16 (382-404) Jack DeRuiter, PhD Dept of Pharmacal Sciences April, 2000

2. Introduction (page 382) • Renal Disease: General Characteristics: • Early Renal Disease: Abnormal urine volume and/or composition (electrolyes, proteins, cells) • Advanced: Edema, electrolyte abnormalities, anemia, etc. • Rate of Progression: Disease-dependent • Disease Course: Transient-fatal: Disease-dependent • Pain: Variable, depending on nature of disease • Renal Disease prominent in: • Diabetes Mellitus • Hypertension • Autoimmune disorders (SLE)

3. KIDNEY STRUCTURE AND FUNCTION GROSS ANATOMY OF THE KIDNEY: (Page 382): • Location: Retroperitoneal • Blood flow: Renal Artery and Renal Vein • Flow from cortex to medulla • Medulla has relatively low blood flow and high metabolism; thus particularly susceptible to ischemic injury • Cardiac Output: 25% • Function: • Filter wastes from blood • Regulate electrolytes and intravascular volume • Modulation of other hormones/regulators • Anatomic/Functional Unit: Nephron

4. Anatomical Location and Gross Structure

5. Kidney: Blood Supply/Ureter

6. Kidney: Cross-Section

7. THE NEPHRON (pages 382, 384) • Glomerulus • Afferent and Efferent arteriole with intervening capillary tuft • Blood filtration site • Renal Tubule • Proximal Convoluted Tubule • Loop of Henle: Consists of descending, thin and thick ascending limbs • Distal Convoluted tubule • Collecting Ducts

8. NEPHRON: Overview 1: Interlobular artery 2: Interlobular Vein 3: Glomerulus/Bowman’s Capsule 4. Distal Tubule 5. Proximal Tubule 6: Loop of Henle 7: Collecting Duct

9. Cortical and Medullary Nephrons Cortical nephrons: 85% -peritubular capillaries encirling all nephron sections Juxtamedullary nephrons: 15% -some peritubular capillaries and vascular loops (vasa recta) which surround loop of Henle which descend into medulla

10. Glomerulus Structure Summary(pages 382-385) • Afferent and Efferent Arterioles • Juxtaglomerular apparatus • Capillary bed: • Endothelial Cells: Fenestrated/negatively charged • Epithelial Cells (“Podocytes”) • Basement Membrane • Mesangium: Intrinsic glomerular cells and macrophages

11. Glomerulus and Glomerular Capillary

12. Nephron: The Glomerulus (pages 382-384)

13. Glomerular Filtration (page 385) • Rate (GFR): 120 mL/min (normal) • Substances “Filtered”: • water, electrolytes (Na, K, etc.), sugars (glucose), nitrogenous waste (urea, creatinine) • Substances “Excluded”: • Substances of size > 70 kDa • Plasma protein bound substances

14. Tubular Resorption (page 385) • Proximal Tubules: GF: 120-125 mL/min • Reabsorption of Na (55%), Cl, phosphate, amino acids, glucose and bicarbonate (85%). Secretion of proton (CA) • Loop of Henle: (30 mL/min) • Na/K/2Cl Cotransporter (25% Na reabsorbed) • Water impermeable: Hypertonic medullary inst • Ca & Mg paracellular diffusion • Distal Tubules: • EDT: Na/Cl cotransporter; Ca/Na counter transport • LDT: Na Channels, K channels, H pump: Aldosterone reg. • Collecting Tubules: 5-10 mL/min • Water channels: Vasopressin regulated • Ureters: 1-2 mL/min (stored inbladder until voiding)

15. Summary of Tubular Resorptive Processes

16. Role of the Kidney: Overview The kidney excretes wastes, maintains fluid and electrolyte homeostasis, and is capable of responding to physiologic needs and variation by generating either a concentrated or dilute urine: • Counter-current multiplier in the loop of Henle • Hypertonic medulary interstitium • Vassopressin and other hormones

17. Regulation of Renal Function (page 387) • Tubuloglomerular feedback • Medullary Vasoconstriction • Medullary Vasodilation • Inhibition of transport in the thick ascending limbs

18. Regulation of Renal Function (page 387) • Tubuloglomerular Feedback: Regulation of GFR in response to solute concentration in the distal tubule: • macula densa (PCT): Afferent arteriolar vasoconstriction in response to high tubular Na (Decr GFR) • Juxtaglomerular apparatus (Afferent): Renin release and angiotensin II formation with low perfusion pressure (Aldosterone secretion and Na and water retention)

19. Regulation of Renal Function (page 387) • Cortical Flow: Adequate to maintain GFR • Medullary Blood Flow and Oxygen demand: • Important for nephron cell survival and function (oxygen is required for ATP, used in trnasporters) • Too high: Disruption of osmolar gradient of counter-current exchange mechanism • Too low: hypoxic injury • Modulators: Table 16-2 (page 387)

20. Regulation of Renal Function (page 387) • Adaptive Changes: • Glomerular hyperfiltration (increased GFR per nephron) nephron loss. ( may progress to chronic renal failure). • Neural and Hormonal regulation: low perfusion results in afferent arteriolar vasodilation and efferent arteriolar vasconstriction • Alteration in Na systemic balance • Renal nerve (sympathetic)

21. The Kidney and Physiologic Regulation: Blood Pressure (pages 385-386) • Macula Densa and Na concentration • Juxtaglomerular Apparatus and Renin release and angiotensin II production • Direct vasoconstriction • Aldosterone Secretion: na and water rentention • Vasopressin and intravascular volume depletion: Enhanced water resorption at the collecting ducts • Morphologic: i.e. number of nephrons, etc.

22. The Kidney and Physiologic Regulation: Calcium Metabolism (page 386-387) • Formation of the active form of vitamin D required for Ca absorption from gut, etc. • Site of Parathyroid Hormone action: Ca retention and phosphate wasting (see earlier endocrine lectures)

23. The Kidney and Physiologic Regulation: Erythropoiesis (page 387) • Erythropoietin stimulates bone marrow production and maturation of RBCs. • Profound anemia in ESRD: • hematocrits 20-25% • Therapy: Erythropoietin administration