Transcript RENAL DISEASE

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)
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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