RENAL DISEASE: Overview of Kidney Structure and Function
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 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
Anatomical Location and Gross Structure
Kidney: Blood Supply/Ureter
Kidney: Cross-Section
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
Glomerulus and Glomerular Capillary
Nephron: The Glomerulus
(pages 382-384)
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)
Summary of Tubular Resorptive Processes
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 countercurrent 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)
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