Diuretics

Objectives

Diuretics

Into: Definitions

(5)

• Diuresis = increase urine flow (H2O)
• Natriuresis = increase Na+ excretion;
• Common usage, diuresis =
• increase Uvol per se and, 
• increased net loss of solute and water

Diuretics

Into: Early and current use

(6)

• Early Use of diuretics
• Old class of drugs-- first used in 16th century
• Most commonly prescribed class of drugs in U.S
• Used for a large number of pathological condition
• fluid retaining pathologies
• non-fluid retaining pathologies

Diuretics

Body Fluid

Body Fluid Compartments

(9)

• 60-65% of boldy weight
• Body Fluid Compartments
• Intracellular- fluid inside cells
• Accounts for 70 % of total body fluid
• Extracellular- all fluid outside cell walls
• Accounts for 25 % total body fluid
• Divided
• Interstitial fluid- between cell wall and vascular compartment--20 % total body fluid
• Plasma- fluid contained in vascular compartment-5 % total body fluid

Diuretics

Body Fluid

Water Movement Between Compartments

(2)

• Osmotic gradient-from less to more concentrated compartment
• Vascular mechanisms to maintain BV (ISF—Plasma) 

Diuretics

Body Fluid

• 60-65% of boldy weight
• Body Fluid Compartments
• Water Moverment Btwn Cells
• Loss From Plasma Compartment
• Use the kidneys to indirectly reduce ISF

Diuretics

Body Fluid

Loss From Plasma

(3)

• Body water is lost from plasma compartment (PV) by action of the  kidneys.
• This draws more fluid from the interstitial space by vascular mechanisms designed to maintain BV.
• Reduces Interstitial fluid

Diuretics

Clinical Use: Edematous States

(8)

• Goal of Diuretic Therapy- Reduce PV/BV
• Therapeutic end point based on pathology.
• Edematous States-
• CHF- 
• Kidney Disease- 
• Hepatic Ascites- accumulation
• Pulmonary Edema- 
• Increased CSF Pressure

Diuretics

Clinical Use: Edematous States

CHF

(3)

• Reduce overall extracellular fluid volume
• Unload heart.
• Goal-reduce load on heart by decreasing PV/BV

Diuretics

Clinical Use: Edematous States

Kidney Disease

• Aid failing kidney in excretion function of Na/H20
      

Diuretics

Clinical Use: Edematous States

hepatic Ascites

(5)

• Abdominal fluid accumulation iver dysfunction;
• Goal: reduce fluid volume in abdomen. 
• major cause cirrhosis
• elevated hepatic pressure 
• reduced plasma protein concentration

Diuretics

Clinical Use: Edematous States
Pulmonary 

(2)

• Increased pulmonary pressure- 
• Goal - Reduce fluid accumulation in lungs.

Diuretics

Clinical Use: Edematous States
Increased CSF Pressure 

• Draw volume from brain into vascular compartment for elimination for excretion
• Goal- reduce CSF volume

Diuretics

Clinical Use: Non-Edematous States

HTN

(6)

• reduced PV/BV and peripheral resistance
• Usually first pharmacological therapy for hypertension

• Most common prescribed class of antihypertensive
• Antihypertensive action
• Acute-Reduces cardiac output by decreasing PV/BV
• Chronic-Reduces total peripheral resistance by unknown mechanism(s)

Diuretics

Clinical Use: Non-Edematous States

HTN: Combo Therapy

(3)

• Used in combination to:
• augment antihypertensive effect of other agents,
• counteract reflex antinatriuretic effects of decreased BP in hypertensive patients.

Diuretics

Clinical Use: Non-Edematous States

Electrolyte Imbalance

(5)

• Restores normal elctrolyte levels by altering renal reabsorption/secretion

• ·      Change inappropriate renal handling of electrolytes. 

• hypernatremia
• hypokalemia, 
• hyperkalemia
 

Diuretics

Clinical Use: Critical Concepts

Therapeutic Use of Diuretics

(5)

• edema, general or localized to specific organ system
• reduce interstitial fluid volume –
• non- edematous states
• reduce blood pressure
• alter electrolytes

Diuretics

Clinical Use: Critical Concepts

Goal of Diuretic Therapy

(3)

• Use the kidney to reduce extracellular fluid/plasma volume,
• or alter electrolyte composition of ECF
–
• Generally DO NOT treat underlying pathology, symptom

Basic Renal Process 

Filtration

(6)

•  Bulk flow of protein free plasma
• Through membranes of Bowman’s capsule-glomerular filtrate forms tubular fluid

• All substances except protein and blood cells same concentration as  plasma
• Factors affecting filtration
• size of the molecule,
• charge-- membranes are negatively charged, as are the proteins

Basic Renal Process 

(3)

• Filtration 
• Tubular Reabsorption—Diuretic action

• Tubular Secretion

        

   

Basic Renal Process

Tubular Reabsorption

(4)

• movement from tubular lumen to interstitial fluid
• interstitial fluid into peritubular capillary plasma
• decreases volume excreted; increases volume retained
• Functional effect of diuretics—decreased reabsorption

Basic Renal Process

Tubular Secretion

(3)

• amovement from peritubular plasma to interstitial fluid
• movement from interstitial fluid to tubular lumen
• increases volume excreted; decreases volume retained

Renal Control of Fluid Volume Review

(9)

• Filtration Reabsorption Secretion
• Renal Anatomy 
• Glomerulus
• Proximal Tubule
• 
Loop of Henle
• 
Distal Convoluted Tubule 
• Collecting Tubule
• Diuretics act at nephron segments to decrease sodium reabsorption.
• Water reabsorption decreases in response to sodium.

Renal Function and Anatomy

Function: Filtration of Plasma

(4)

• 180 L/ day
• protein free filtrate
• filtrate contains all plasma substances-
• EXCEPT plasma proteins, protein-bound substances in same concentration as in plasma

Renal Function and Anatomy

Function:Reabsorption of filtered substances

 (3)

Renal Function and Anatomy

Function: Secretion of unfiltered substances

(2)

• occurs by mediated transport or diffusion
• water-passive down osmotic gradient in permeable sections

• Nephron segments
• Each unique characteristics for reabsorption/secretion
• Vary in water permeability

Renal Function

Reabsorption/24 hrs

(9)

• Filtered
• Water 180 L
• Sodium 630
• Excreted
• Water 1.8 L
• Sodium 3.2 g
• % Reabsorbed
• Water 99
•  Sodium 99.9

Renal Function

Reabsorption/24 hrs

Critical Point

• There is a LARGE amount of Na+ and water reabsorbed. 
• Tremendous potential for decreasing body fluid volume by decreasing reabsorption.

Renal Function

Reabsorption

Notes

• Reabsorption of Water and Sodium
• Large volume of water and sodium is filtered by kidneys
• Most reabsorbed in the nephron and returned to the circulation 
• Diuretics the decrease reabsorption, therefore reducing PV
• Critical Point- large volume of Na+ reabsorbed. Decreasing the amount reabsorbed can result in very large decreases in body fluid volume. 

Renal Function

Segment Specific Mechanisms of Na+ Reabsorption

(6)

• Proximal Convoluted Tubule 
• Na+/H+ Exchanger
• Ascending Limb-Loop of Henle 
• Na+/K+/2Cl- Cotransporter
• Distal Convoluted Tubule 
• Na+/Cl- Cotransporter
• Collecting Duct 
• Hormone-Aldo, AVP Na+ Channels
• CRITICAL POINTS: Nephron segments
use different mechanisms to transport
Na+. Diuretics are specific to transport mechanism.

Renal Function

Segment Specific Mechanisms of Na+ Reabsorption

Notes

(8)

• Proximal convoluted tubule
• Sodium/hydrogen exchanger and carbonic acid
• Ascending Limb of Loop of Henle
• Na+/K+/2Cl cotransporter
• Distal Convoluted Tubule
• Na+/Cl cotransporter
• Collecting Duct
• Increased Na+ reabsorption in response to Aldosterone
• Presence of Na+ Channels on luminal side of epithelial cells
• Critical Points
• Different nephron segments utilize different and unique mechanisms of Na+ reabsorption.
• Different diuretics act specifically on these transport systems to reduce Na+ reabsorption.
• Functional Significance-
• Site of action in nephron determines potential natriuretic efficacy of diuretic.

Renal Function

Water Reabsorption

• Osmotic Gradient
• Gradient created by Na+ Reabsorption
• Water moves from lumen to interstitial space down osmotic gradient
• Critical Point - Water reabsorption tied to Na reabsorption

Renal Function

Water Reabsorption

Notes

(9)

• Water moves down osmotic gradient
• In nephron, water moves through and between cells
• In most segments
• Permeability varies through nephron 
• Sodium reabsorption increases osmolality of interstitial fluid adjacent to the nephron and decreases osmolality of luminal fluid.
• Water moves down this concentration gradient from the lumen to the interstitial fluid.
• Subsequently returned to vascular compartment by absorption into the peritubulary capillaries.
• Critical Point-
• Water reabsorption directly related to Na+ reabsorption. 
• Decreasing sodium reabsorption reduces water reabsorption.  

Renal Function

Critical Points

Renal Handling of Sodium/Water

(4)

• Sodium and water freely filterable- most reabsorbed
• Sodium reabsorption in nephron 
– mediated by SPECIFIC AND DIFFERENT mechanisms along nephron
• Water reabsorption is secondary to sodium and follows osmotic gradient
• Decreased sodium reabsorption=diuresis and natriuresis
•