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RENAL DISEASE:Overview of Kidney Structure
and Function
Pathophysiology of Disease: Chapter 16 (382-404)Pathophysiology of Disease: Chapter 16 (382-404)
Jack DeRuiter, PhD
Dept of Pharmacal Sciences
April, 2000
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)
KIDNEY STRUCTURE AND FUNCTIONGROSS 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
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
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
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
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
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
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)
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
Regulation of Renal Function (page 387)
• Tubuloglomerular feedback
• Medullary Vasoconstriction
• Medullary Vasodilation
• Inhibition of transport in the thick ascending limbs
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)
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)
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)
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.
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)