Renal Insufficiency and Dialysis

Urinary Incontinence
Urinary Tract Calculi

From: Kelly CR & Landman J.(Eds.) The Netter Collection of Medical Illustrations, 2E Vol 5- Urinary System.
Philadelphia PA: Saunders, 2012.
 Renal Insufficiency and
Dialysis

Marc Imhotep Cray, M.D. 2

Acute kidney injury (Acute renal failure)
 Acute kidney injury is defined as an abrupt decline in renal function as measured by
↑creatinine and ↑BUN
Prerenal azotemia Due to ↓ RBF (eg, hypotension)  ↓GFR
 Na+/H2O and BUN retained by kidney in an attempt to conserve volume  ↑BUN/Cr
ratio (BUN is reabsorbed, creatinine is not) and ↓ FENa

Intrinsic renal failure Generally due to acute tubular necrosis or ischemia/toxins; less
commonly due to acute glomerulonephritis (eg, RPGN, hemolytic uremic syndrome) or acute
interstitial nephritis
 In ATN, patchy necrosis  debris obstructing tubule and fluid backflow across necrotic
tubule  ↓ GFR
 Urine has epithelial/granular casts
 BUN reabsorption is impaired  ↓BUN/creatinine ratio

Postrenal azotemia Due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies)
 Develops only with bilateral obstruction
Acute kidney injury (AKI) cont.

Le T and Bhushan V. First Aid for the USMLE Step 1 2016.McGraw-Hill, 2016.

Marc Imhotep Cray, M.D.

Consequences of renal failure
Consequences (MAD HUNGER):
 Renal failure: Inability to
Metabolic Acidosis
make urine and excrete
Dyslipidemia (especially ↑ triglycerides)
nitrogenous wastes
Hyperkalemia
2 forms of renal failure:
Uremia—clinical syndrome marked by
 acute (eg, ATN) and
 ↑BUN:
 chronic (eg, HTN, DM,
o Nausea and anorexia
congenital anomalies)
o Pericarditis
o Asterixis
o Encephalopathy
o Platelet dysfunction
Na+/H2O retention (HF, pulmonary edema,
hypertension)
Growth retardation and developmental delay
Erythropoietin failure (anemia)
Marc Imhotep Cray, M.D. Renal osteodystrophy
 QUESTION:
What is the difference between azotemia and uremia?
Azotemia is a medical condition characterized by abnormally high levels of
nitrogen-containing compounds (such as urea, creatinine, various body waste
compounds, and other nitrogen-rich compounds) in the blood.
It is largely related to insufficient or dysfunctional filtering of blood by the
kidneys. It can lead to uremia if not controlled.

Uremia in current usage represents the entire constellation of signs and

symptoms of chronic renal failure, including nausea, vomiting, anorexia, a
metallic taste in the mouth, a characteristic odor of breath, pruritus, urea frost
on the skin, neuromuscular disorders, pain and twitching in muscles,
hypertension, edema, mental confusion, and acid-base and electrolyte
imbalances.
Nephrologist prefer to call this the uremic syndrome.
Marc Imhotep Cray, M.D. 6
Effect of Renal Insufficiency on Drug Action
 Many drugs and drug metabolites are excreted via kidney so
changes (e.g., advanced age, disease) that alter renal function
affect elimination (half-life) of many agents

 Blood levels of a drug or its metabolites are greater when

decreased renal clearance exists than during normal renal
clearance
 This change is clinically relevant for drugs eliminated primarily by kidneys
o Even more critical for drugs with a small therapeutic index
 Sometimes effect of renal insufficiency on a drug metabolite
(e.g., normeperidine) is more important than that on drug itself
(i.e., meperidine)
Marc Imhotep Cray, M.D. 7
Effect of Renal Insufficiency on Drug Action(2)
 Renal function usually declines with age so elderly patients
are often given reduced doses of drugs eliminated mainly via
kidneys

 Examples of altered drug action in renal insufficiency are

 enhanced hyperkalemia with K+-sparing diuretics or NSAIDs
 delayed or decreased diuretic effectiveness and
 greater risk of NSAID-induced GI bleeding

Marc Imhotep Cray, M.D. 8

Effect of Renal Insufficiency on Drug Action (3)

Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014

9
Effect of Hemodialysis on Drug Action
Hemodialysis is used
 as maintenance therapy for patients with renal failure and
 to clear toxic substances from blood of patients who ingested poisons
or overdoses of drugs

 Fundamental physiologic principle in dialysis is that of a solute moving

across a semipermeable membrane in a direction and at a rate consistent
with concentration and osmotic gradients
 Principle is basis for operation of artificial or mechanical kidneys

 If a patient receives therapy with a drug that can be dialyzed

(i.e., pass through membrane), amount lost during dialysis must be
considered, and supplementary doses may be needed to replace lost drug
Marc Imhotep Cray, M.D. 10
Hemodialysis

Raff RB, Rawls SM, Beyzarov EP. Netter's

Illustrated Pharmacology, Updated Edition.
Saunders, 2014
11
Currently Known Dialyzable Substances

Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014

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 Urinary Incontinence
Urinary Tract Calculi

Marc Imhotep Cray, M.D. 13

Urinary Incontinence
Urinary retention is normally under autonomic or voluntary
control
 Incontinence (an increased stimulus to void, a
decreasedability to prevent voiding, or both) results when
these pathways are interrupted or are overactivated or
underactivated, or when smooth muscle of bladder
contracts weakly, incoordinately, or inappropriately

Although incontinence is not life threatening, it has significant

medical and social consequences
 It is often cited as a primary reason for inability of families
to care for elders at home
Marc Imhotep Cray, M.D. 14
Urinary Incontinence (2)
 Drug treatment options (far from ideal) include:
 those that reduce bladder contraction, such as cholinergic
antagonists
o (e.g., oxybutynin, prophantheline, tolterodine)
 those that increase bladder outlet function, such as α-
adrenoceptor agonists
o (e.g., phenylpropanolamine, pseudoephedrine); and
 those for which mechanism is not fully understood, such as
o tricyclic antidepressants (possibly related to
anticholinergic actions) and
o estrogens (in postmenopausal women)
Marc Imhotep Cray, M.D. 15
Urinary Incontinence (3)

Marc Imhotep Cray, M.D. 16

Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014
Case 55-Urinary Incontinence
A 48-year-old Caucasian woman you have been treating for several years comes
to your family medicine practice and seems embarrassed. She complains of
urinating at least 10 times a day and 3 to 4 times at night and states it is
interfering with her business and social life. She indicates her problem, which
she says is “due to her getting older,” began about 2 years ago. She has tried
several things to help, including drinking only one cup of coffee in the morning
and total avoidance of liquid after 6 PM. She has begun wearing pads to avoid
the embarrassment of leakage. She describes being in an important business
meeting and having to get up and leave to go to the bathroom. She constantly
worries about the location of the nearest bathroom and has avoided social
events like her son’s soccer games, which are on an open field with no facilities.

Marc Imhotep Cray, M.D. 17

Case 55 cont.
Upon further questioning she denies leakage with coughing, sneezing, or
laughing. She denies any dysuria, hematuria, or feeling of incomplete voiding.
She is monogamous without any prior history of sexually transmitted
infections (STIs). You assure her the problem is not due to “getting old” and
that there are treatable medical causes for the problem. Your physical
examination is negative for STIs, vulvar or vaginal inflammation/infection/
trauma, and cystocele. You order a urinalysis which comes back normal. You
prescribe a trial of oxybutynin.
_ What are the causes of overactive bladder?
_ What is the mechanism of action of oxybutynin?
_ What are the different classes of agents used in the treatment of the
different kinds of urinary incontinence?

Marc Imhotep Cray, M.D. 18

 Summary:
• Urge incontinence (see following for other forms of UI) is
caused by contraction of the bladder such that urine passes the
urethral sphincter at the wrong time.
• Oxybutynin is an anticholinergic drug that blocks muscarinic
cholinergic receptors. M3 cholinergic receptors are responsible for
the direct activation of the detrusor muscle. Oxybutynin
decreases frequency of symptoms, and delays initial desire to
void.

Marc Imhotep Cray, M.D. 19

Clinical Correlation
There are several types of urinary incontinence and they have different
causes.
Urge incontinence as described in this case is typified as urinating more
than eight times a day accompanied by a sudden and intense urge to
urinate, frequently followed by involuntary loss of urine. The detrusor
muscle contracts well before the bladder has filled and may give a warning
of only a few seconds before the bladder sphincter muscle relaxes.
The fundamental problem seems to be neuromuscular in origin.
Contraction of the detrusor muscle is mediated by M3 cholinergic
receptors. Urge incontinence may be caused by urinary tract infections,
bladder irritants, bowel disease, Parkinson disease, Alzheimer disease,
stroke, or nervous system damage associated with multiple sclerosis.
If there’s no known primary cause, urge incontinence is also called
overactive bladder.

Marc Imhotep Cray, M.D. 20

Clinical Correlation cont.
Stress urinary incontinence (SUI) occurs upon sneezing,
laughing, coughing, or other maneuvers that increase intra-
abdominal pressure in the presence of a weakened bladder
sphincter. Urethral pressures, prolapse conditions, and
congenital and acquired sphincter dysfunction all contribute to
SUI pathophysiology.
In women, childbirth, pregnancy, and menopause can cause
stress incontinence.
In men, prostate removal is a cause.

Marc Imhotep Cray, M.D. 21

Clinical Correlation cont.
Overflow incontinence is a frequent near-constant loss of urine
caused by inability to void. This usually has an anatomical or
neural cause that interferes with normal emptying of the bladder.
Mixed incontinence refers to a combination of types.
The most common type of urinary incontinence in older women is
a mixture of urge and stress incontinence. Treatments include
lifestyle and behavioral modifications, drugs, and surgery.
Often the detailed history and examination is sufficient to give a
presumptive diagnosis; however, various testing may be needed to
rule out other contributing or causative etiologies. On occasion
diagnostic testing, radiographic testing, and laboratory testing may
be required as well.
Marc Imhotep Cray, M.D. 22
Urinary Tract Calculi (Kidney Stones)
 Urinary calculi are hardened crystals composed of a nucleus (often urate)
and surrounding layers of precipitated minerals, such as calcium and
magnesium salts, and other components of the urine (including
metabolites of drugs excreted in the urine)

 Stones are usually found in kidney, but they also occur in ureter and
bladder (usually passed from kidney)

 Urinary calculi occur in all age groups but primarily in persons aged
between 20 and 55 years

 Treatment (surgical or pharmacologic) depends on the cause, size, and

location of the stone

Marc Imhotep Cray, M.D. 23

 Kidney Stones (2)
 Two common types for which drugs are used are due to
hypercalciuria and hyperuricuria

 Drugs for hypercalciuria include

 sodium cellulose phosphate (inhibits calcium reabsorption)
and
 thiazides (mild diuresis stimulates convoluted tubule
reabsorption of calcium)
 Drugs for hyperuricuria include
 allopurinol (decreases urate formation) and
 alkali (increases urinary citrate, which inhibits stone
formation)
Marc Imhotep Cray, M.D. 24
Urinary Tract Calculi (3)

Marc Imhotep Cray, M.D. 25

Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Saunders, 2014
 See next slide for sources and links to additional study tools and resources.
Marc Imhotep Cray, M.D. 26
 Sources and further study:
eLearning
Renal cloud folder tools and resources

MedPharm Guidebook:
Unit 9 Drugs Used to Affect Renal Function
Renal Pharmacology eNotes
Clinical Pharmacology Cases 7, 8, & 55 (Learning Triggers)

Textbooks
Brunton LL, Chabner BA , Knollmann BC (Eds.). Goodman and Gilman’s The Pharmacological
Basis of Therapeutics. 12th ed. New York: McGraw-Hill, 2011
Katzung, Masters, Trevor. Basic and Clinical Pharmacology, 12th ed. New York: McGraw-Hill,
2012
Mulroney SE. and Myers AK. Netter's Essential Physiology. Philadelphia: Saunders, 2009
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition.
Philadelphia: Sanders, 2014
Toy E C. et.al. Case Files-Pharmacology Lange 3rd ed. New York: McGraw-Hill 2014.
Marc Imhotep Cray, M.D. 27