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

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RENAL DISEASEOverview of Kidney Structure and
FunctionPathophysiology of Disease Chapter 16
(382-404)

• Jack DeRuiter, PhD
• Dept of Pharmacal Sciences
• April, 2000

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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)

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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

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Anatomical Location and Gross Structure
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Kidney Blood Supply/Ureter
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Kidney Cross-Section
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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

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NEPHRON Overview

• 1 Interlobular artery
• 2 Interlobular Vein
• 3 Glomerulus/Bowmans Capsule
• 4. Distal Tubule
• 5. Proximal Tubule
• 6 Loop of Henle
• 7 Collecting Duct

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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

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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

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Glomerulus and Glomerular Capillary
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Nephron The Glomerulus (pages 382-384)
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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 gt 70 kDa
• Plasma protein bound substances

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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)

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Summary of Tubular Resorptive Processes
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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

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Regulation of Renal Function (page 387)

• Tubuloglomerular feedback
• Medullary Vasoconstriction
• Medullary Vasodilation
• Inhibition of transport in the thick ascending
  limbs

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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)

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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)

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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)

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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.

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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)

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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