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

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 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)

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