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 )

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Renal Disease: General Characteristics:

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Early Renal Disease: Abnormal urine volume and/or composition (electrolyes, proteins, cells)

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Advanced: Edema, electrolyte abnormalities, anemia, etc.

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Rate of Progression: Disease-dependent Disease Course: Transient-fatal: Disease-dependent Pain: Variable, depending on nature of disease Renal Disease prominent in:

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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

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Flow from cortex to medulla Medulla has relatively low blood flow and high metabolism; thus particularly susceptible to ischemic injury Cardiac Output: 25% Function:

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Filter wastes from blood

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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)

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Glomerulus

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Afferent and Efferent arteriole with intervening capillary tuft

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Blood filtration site Renal Tubule

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Proximal Convoluted Tubule Loop of Henle: Consists of descending, thin and thick ascending limbs

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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