2nd Urinary System

Renal System

Renal System

• Filters blood

• Regulates ECF volume & composition

• Excretes metabolic waste products (urea, etc.)

• Produces hormone (e.g. erythropoietin, 1,25- dihydroxyvitamin D3)

Ureter

Muscular tube that transports urine to the urinary bladder

Urinary bladder

Stores urine until urination/micturition

Detrusor muscle

What is the smooth muscle along the wall of the urinary bladder that relaxes when the bladder is filled with urine and contracts when it is time to empty the bladder and urinate?

a. Detrusor muscle

b. Internal urethral sphincter

c. External urethral sphincter

d. Muscular layer

Nephron

• Functional unit of the kidney

• Approximate no. of nephrons/kidney:

  • Cattle: 4,000,000

  • Pig: 1,250,000

  • Dog: 415,000

  • Cat: 190,000

  • Human: 1,000,000

• Glomerulus

• Bowman’s capsule

• Renal / Malphigian corpuscle → Bowman’s capsule + Glomerulus

• Proximal tubule

• Loop of Henle

• Distal tubule

• Collecting duct

• Afferent arteriole

• Efferent arteriole

What are the parts of the nephron?

Glomerulus

A tuft of capillaries that performs blood filtration

Bowman’s capsule

Expanded blind end of the tubule that encloses the glomerulus

Renal / Malphigian corpuscle

Bowman’s capsule + glomerulus is called?

Collecting Duct

Conveys urine from nephron into the renal pelvis

Afferent arteriole

Conducts blood to the glomerulus

Efferent arteriole

Conducts blood away from the glomerulus

Diuretics

• Medications that promote diuresis (increased urine production)

• Indication: conditions that are characterized by fluid retention (i.e., edema or ascites)

  • Heart failure

  • Inflammation or trauma

  • Hypoproteinemia

  • High blood pressure

• Leads to the reduction of preload, ascites, and pulmonary edema

• Diuretics (except for osmotic diuretics) are the most commonly used class of drugs for treating heart failure

• Reduction of preload

• Ascites

• Pulmonary edema

Diuretics leads to?

Diuretics, except osmotic diuretics

Most commonly used class of drugs for treating heart failure

• Conditions characterized by fluid retention (edema, ascites)

  • Heart Failure

  • Inflammation or Trauma

  • Hypoproteinemia

  • High blood pressure

Indications of Diuretics

• Increased urine output & excretion of electrolytes & H2O

• This can potentially lead to electrolyte imbalances (Na, Cl, K, Ca, Mg)

• Reduced pulmonary or systemic fluid retention in CHF

What are the effects of Diuretics

Functional kidney

What does the use of diuretics requires to be effective?

Classifications of Diuretics

• Natriuretic agents

• Loop diuretics

• Potassium sparing diuretics

• Osmotic diuretics

• Natriuretic agents

• Loop diuretics

• Potassium sparing diuretics

What are the most commonly used in veterinary medicine

Natriuretic Agents

• MOA: Promote natriuresis (urinary excretion of Na+) by suppressing the kidney’s ability to reabsorb Na+

  • A. Carbonic anhydrase inhibitors

  • B. Thiazides

Carbonic anhydrase inhibitors

• MOA: Inhibit carbonic anhydrase in the proximal convoluted tubules

• This reduces H+-Na+ exchange, thus, less Na+ is reabsorbed in the tubules

• Effects:

  • Can potentially lead to metabolic acidosis

    • Use only at recommended doses

  • Increases urine pH due to HCO3– retention in the tubular lumen

  • Reduces aqueous humor production

  • Can be beneficial in glaucoma treatment

Metabolic Acidosis

If H+ (and Carbonate?) is not excreted and stays in proximal convoluted tubules, what disease does it cause?

• Glaucoma treatment

• Aqueous humor

Carbonic anhydrase inhibitors can be beneficial to _____ due to its effect of reduction of ____ ____ production.

Types of Carbonic Anhydrase Inhibitors

• Acetazolamide

• Dichlorphenamide

• Methazolamide

• Dorzolamide

Dorzolamide

What Carbonic Anhydrase Inhibitors is used for ophthalmic use / topical?

Thiazides

• MOA:

  • Inhibits Na+ & Cl

  • Reabsorption in the early distal tubule via its inhibition of sodium- chloride co-transporter (NCC)

• Indication:

  • Edema of most types (esp. cardiac and hypoproteinemic edema)

  • May be given concurrently with K- sparing diuretics because of its hypokalemic effect

• Adverse Effects:

  • Electrolyte imbalances (hypokalemia, hypomagnesemia & hypercalcemia)

  • Hyperglycemia - thiazides contribute to insulin resistance

• Edema of most types

• Can be given concurrently with K-sparing diuretics because its hypokalemic effect

Indication of Thiazides

• Electrolyte imbalances

  • Hypokalemia

  • Hypomagnesemia

  • Hypercalcemia

• Hyperglycemia

Adverse effects of Thiazides

Thiazides

Contributes to insulin resistance

• Chlorothiazide

• Hydrochlorothiazide

Examples of Thiazides

Loop Diuretics / High Ceiling Diuretics

• MOA: inhibits the sodium-potassium- chloride co-transporter (NKCC2) protein in the thick ascending limb of the loop of Henle

• A large amount of the ions are not efficiently reabsorbed, leading to a potent and effective diuretic action vs. other classes of diuretics

• With rapid onset of effect

Loop Diuretics / High Ceiling Diuretics

Most effective and commonly prescribed diuretics

• Furosemide / Frusemide

• Bumetanide

• Ethacrynic acid

• Torsemide

Examples of Loop Diuretics / High Ceiling Diuretics

Furosemide / Frusemide

Most commonly used diuretic in veterinary medicine

Furosemide / Frusemide

• Indication: most edematous conditions

• Injectable and oral formulations are available

• Adverse side effects:

  • Electrolyte disturbances (e.g. K, Na, Ca, & Mg)

    • Hypokalemia, high Ca levels can occur

  • Dehydration, weakness, shock, low BP

  • Ototoxicity (hearing loss) - Avoid concurrent use with aminoglycosides (antibacterial with ototoxic effect)

Potassium-Sparing Diuretics

• Used in combination with thiazides & other more potent diuretics to avert excessive K loss from these agents

• Spironolactone

• Triamterene

• Amiloride

Examples of Potassium-Sparing Diuretics

• Spironolactone

• MOA: antagonizes aldosterone in the collecting duct

• Aldosterone - promotes Na+ (and H2O reabsorption) & K+ excretion

Triamterene & Amiloride

• Mild diuretics

• Action is not associated with aldosterone

• MOA: inhibit the sodium-potassium exchange channels in the renal tubules (specifically, the epithelial sodium channels, ENaC) so that more Na remains in the urine

Osmotic Diuretics

• Substances filtered by the glomerulus and remain in the tubular fluid

• MOA: They osmotically attract H2O at the renal tubules leading to diuresis

Mannitol

Example of Osmotic Diuretics

Mannitol

• Indications

  • Cerebral edema* (decreases intracranial pressure)

  • Acute glaucoma (reduces intraocular pressure)

  • Acute renal failure (promotes urine output)

• Contraindications

  • Mannitol can exacerbate certain aspects of CHF

    • It increases circulatory volume and can worsen congestion and fluid build-up

    • It can increase BP and potentially put additional strain on the heart, which is counterproductive in CHF

• Cerebral edema* (decreases intracranial pressure)

• Acute glaucoma (reduces intraocular pressure)

• Acute renal failure (promotes urine output)

Indications of Mannitol

• Mannitol can exacerbate certain aspects of CHF

  • It increases circulatory volume and can worsen congestion and fluid build-up

  • It can increase BP and potentially put additional strain on the heart, which is counterproductive in CHF

Contraindications of Mannitol

Mannitol

Best for cerebral edema

Action and Effect of Mannitol in Cerebral Edema

Furosemide

A 10-year-old male Doberman was brought into the clinic for dyspnea and coughing. Tests reveal that the dog has left-sided heart failure.

What medication would be likely prescribed for the dog?

a. Mannitol

b. Furosemide

c. Dextromethorphan

d. Acetylcysteine

Urolith

What do u call urinary stones or calculi

Urolith

• Abnormal mineral masses in the urinary tract

• Referred to as nephroliths, ureteroliths, cystoliths or

  urethroliths depending on the location

• Struvite

  • Often associated with urinary tract infections (UTIs) and is composed of Mg, ammonium, and phosphate.

• Calcium

  • Most common type and is typically composed of calcium oxalate

• Urate

  • Forms when there is an excessive amount of uric acid in the urine

• Cystine

  • Forms rarely due to a genetic disorder known as cystinuria, which causes the buildup of the amino acid cystine in the urine

Types of Urolith

Struvite

Often associated with urinary tract infections (UTIs) and is composed of Mg, ammonium, and phosphate.

Calcium

Most common type and is typically composed of calcium oxalate.

Urate

Forms when there is an excessive amount of uric acid in the urine.

Cystine

Forms rarely due to a genetic disorder known as cystinuria, which causes the buildup of the amino acid cystine in the urine

Outcomes of Uroliths

• if + in urinary bladder: hematuria, dysuria

• If + in urethra: obstruction

Causes of Uroliths

• Diet

• Bacterial infection of the urinary tract

• Dehydration

• Underlying medical condition

Dissolves and helps prevent formation of struvites

Urinary Acidifiers — MOA

• Methionine

• Ammonium Cl

Examples of Urinary Acidifiers

Treatment of calcium oxalate, cystine, & ammonium urate crystals

MOA of Urinary alkalinizers

Potassium citrate

Examples of Urinary alkalinizers

Decrease uric acid production, thus helping decrease the formation of ammonium urate uroliths

MOA of Xanthine oxidase inhibitors (preventive)

Allopurinol

Examples of Xanthine oxidase inhibitors (preventive)

Urinary Incontinence

Loss of voluntary regulation of micturition

Categories of Urinary Incontinence

• Neurogenic disorders

• Non-neurogenic disorders

Neurologically-cause Incontinence

May be due to spinal cord trauma, nervous system tumors, nervous system degeneration

Non-Neurogenic Disorders

Due to congenital or acquired anomalies of the lower urinary tract

Types of Non-Neurogenic Disorders

• Congenital

• Acquired

Congenital Non-Neurogenic Disorders

Ureter ends in abnormal places

Acquired Non-Neurogenic Disorders

May arise from urolithiasis, neoplasia, postsurgical adhesions, etc.

Bladder hypocontractility

Cholinergic agonists like bethanechol promote voiding of urine by stimulating acetylcholine action

Bladder hypercontractility

Anticholinergic agents like propantheline and butylhyoscine have antispasmodic action

Urethral Incompetence or Urinary Incontinence

• Result in involuntary leaking of urine

• Due to loss of estrogen

Phenylpropanolamine

Treatment of Urethral Incompetence or Urinary Incontinence

Phenylpropanolamine

• An alpha-adrenergic agonist that increases the tone & contractility of urethral sphincter muscles

• It is often the first-line treatment for urinary incontinence in dogs

Spayed Females

Urinary incontinence is more common in this group of dogs:

a. Females

b. Spayed females

c. Males

d. Neutered males

Summary of Diuretics

• Natriuretic Agents

  • Carbonic Anhydrase Inhibitors

    • Acetazolamide

    • Dichlorphenamide

    • Methazolamide

    • Dorzolamide

  • Thiazides

    • Chlorothiazide

    • Hydrochlorothiazide

• Loop Diuretics

  • Furosemide / Frusemide

  • Bumetanide

  • Ethacrynic Acid

  • Torsemide

• Potassium Sparing Diuretics

  • Spironolactone

  • Triamterene

  • Amiloride

• Osmotic Diuretics

  • Mannitol

Drugs for Uroliths

• Urinary Acidifiers

  • Methionine

  • Ammonium Cl

• Urinary Alkalinizers

  • Potassium citrate

• Xanthine Oxidase Inhibitors — decrease uric acid

  • Allopurinol

Drugs for Urinary Incontinence

• Phenylpropanolamine — 1st choice

• Bladder hypocontractility

  • Cholinergic agonist

    • Betanechol

• Bladder hypercontractility

  • Anticholinergic agents

    • Propantheline

    • Butylhyoscine