MENNONITE
AT
Pathophysiologic
Basis of Health Deviation 437
The
Renal and Urologic Systems
(My
thanks to Barbee Bancroft, from whose lectures the first part of this handout
was prepared.)
Overview
of renal anatomy and physiology
Embryologically:
Ears and kidneys are formed from the same
tissue (oto-renal axis)
Drugs:
both oto- and nephro-toxic
Check ears:
if abnormal, also check for abnormal kidneys
Located in the retroperitoneal space
between T12 and L3
Consists of the renal parenchyma (cortex,
medulla, and renal pelvis) plus the associated structures (ureters, bladder,
urethra)
1. Cortex:
almost all of glomeruli are here (these blood vessels dont regenerate)
diffuse cortical necrosis ---> renal
failure (blood vessels/glomeruli destroyed)
causes of diffuse cortical necrosis: chronic diseases, such as lupus, diabetes
glomerulonephritis: not a pathogen; can occur post-GABHS
due to autoimmune response, such as rheumatic heart disease); 2-hit
CVA tenderness
2. Medulla:
contains ducts (loops of Henle and
collecting ducts where we concentrate urine)
tubulointerstitial
disease (nephritis):
often drug-induced (methacillin, gentamycin, long-term Tylenol use (>
4 Gm/day X 3 yrs), NSAIDS); S/Sx:
inability to concentrate urine
3. Renal
pelvis (pyeles)
pyelonephritis: cause:
ascending infection from urinary tract (usually E. Coli, Klebsiella,
staphylococcus); female > male, age 3 mo - 65 yr.; S/Sx: back pain (1 hit CVA tenderness)
check urine for casts = upper
urinary tract problem (casts include WBC segs)
if RBCs present, but no casts = problem is
in ureter on down (stone)
4. Nephron
Basic functioning unit of the kidney is the
nephron
Consists of the renal corpuscle (glomerulus
and Bowmans capsule) and the renal tubular system (proximal convoluted tubule,
loop of Henle, distal convoluted tubule, and the collecting duct)
1.5 million nephrons/kidney
In polycystic kidney disease, only 5% of
the nephrons are involved, but destroy the entire kidney
Glomerulus:
afferent (into) arteriole: maintained in vasodilated state by the
prostaglandins
efferent (exit) arteriole: maintained in vasoconstricted state by
Angiotensin II
Together, the arterioles maintain the
pressure needed for filtration.
Increased pressure pushes out filtrates.
In uncontrolled diabetes mellitus:
- Increased blood sugar --->
increased prostaglandins ---> increased dilation of afferent arteriole
- Increased blood sugar --->
increased angiotensin II ---> increased constriction of efferent arteriole
- Result: lots in, little out ---> increased
pressure in glomerulus (= intraglomerular hypertension) ---> increased
filtration rate
This will appear as microalbumin.
Monitor routinely in DM
can pick up early by checking urine for
microalbuminuria
if wait to see albumin in dipstick urine,
it is too late: already on way to
end-stage renal disease (ESRD)
if microalbuminuria shows up, need to start
the patient on an ACE-inhibitor (-pril drug) to slow production of
angiotensin II ---> dilate efferent arteriole ---> decreases
intraglomerular pressure
50% of Type I diabetics go into renal
failure
High risk of renal disease if DM with
family history of HTN
If cant take ACE inhibitors, can use
angiotensin II inhibitors (-sartan drugs, such as Cozaar)
NSAIDs:
dont give with ACE-inhibitors
NSAIDs constrict the afferent blood vessel;
if on ACE-Inhibitor also, the dilates the efferent blood vessels ---> sodium
and water back up
NSAIDs will negate the antihypertensive
effect of ACE-Inhibitors; can cause elevated blood pressure
NSAIDs can make the patient refractory to
blood pressure meds (BP goes up and you cant get it down with increased meds)
NSAIDs:
#1 cause of peripheral edema (increase dose, increase problem)
If have to use NSAID in a kidney
patient, use Clinoril; NEVER use Toradol.
Four drugs are considered nephrotoxic:
- NSAIDs
- ACE (angiotensin-converting enzyme)
- aminoglycosides
- radiocontrast dye
Bowmans capsule: first part of tubular system
Tubular cells
- line the tubules; are epithelial cells, so can regenerate
So, with acute tubular necrosis (ATN),
tubular cells died ---> renal failure due to obstruction (clogging)
Cisplatinol ---> ATN, so flush
(can use Mannitol)
Hydrate right before a AAA (aortic
abdominal aneurysm) repair
Heart failure, gentamycin ---> ATN
Loop of Henle: able to concentrate urine
Major functions of renal system:
1. Regulate
water, solutes, electrolytes, and acid-base balance
2. Secrete
renin (If too much estrogen ---> increased renin release ---> increased
BP; this is what happened with the old
BCPs)
3. Aid
in Vitamin D metabolism (activates vitamin D from skin)
4. Secrete
erythropoietin (for RBC production)
Overview
of the hormones affecting the kidney
1. Located in the afferent arteriole are
specialized cells that respond to pressure; these baroreceptors are called the
juxtaglomerular apparatus (JGA)
If
the patient is hypovolemic, the following events will happen:
Decreased
volume ---> decreased BP ---> JGA release renin ----> liver to produce
angiotensin I ---> to the lungs to be converted into angiotensin II via
angiotensin converting enzyme (ACE)
(local
ACE also present in kidneys and heart)
Angiotensin II is a potent hormone that
does the following:
·
tenses the angios (increases BP)
·
Stimulates the adrenal cortex to
release aldosterone; aldosterone works at the distal tubule and the collecting
duct to help reabsorb extra water and electrolytes (Na and Cl in particular)
and to get rid of K+
·
potent growth hormone
-
causes heart to have large left ventricle, increasing the risk of stroke and
v-fib
-
can also destroy kidney, leading to kidney failure
-
can cause idiopathic pulmonary fibrosis
ACE-Inhibitors:
stop conversion of angiotensin I to II
vasodilator
diuretics
decrease the size of the left ventricle
decrease risk of kidney failure and
pulmonary fibrosis
*** DONT give to pregnant women: stops growth
Side effects: dry cough (decrease ACE, increase bradykinin,
a bronchoconstrictor); occurs in 20-40% of women and 1-5% of men; 30% of the
cough sx. will disappear.
Treatment for cough: Cromolyn and Tilade, mast cell stabilizers,
will help stop the cough, OR change to an Angiotensin II inhibitor.
2. Hypovolemia
and/or increased osmolality stimulates osmoreceptors in the hypothalamus which
send a message to the posterior pituitary to release antidiuretic hormone
(ADH). ADH works on the distal tubule
and collecting duct to conserve free water (no sodium).
Beer
inhibits ADH; morphine increases ADH.
Functional
Overview
1. Filtration: passive transport of materials from the blood
through the glomerulus to the tubular system = 125 ml/min or 20% of
plasma. This amounts to 180 L/day; only
material of a certain size.
125
ml/min in 30 year old. Lose 1
ml/min/year, so 75 ml/min in 80 year old.
Thus, slower
going through filtration membrane. This
is the rationale, for drug dosing in the elderly: start low and go slow.
2. Tubular reabsorption: a process by which substances are transferred
from the renal tubular lumen into the small peritubular capillary network
surrounding the tubular system. 178
L/day is reabsorbed: 144 L/day through the
proximal tubule and 34 L/day through the distal tubule and loop of Henle
Thus: filtration =
180 L/day
- reabsorption = 178
L/day
Excretion = 2 L/day
Urine
output:
Oliguria
= 50-400 cc/24 hours
Anuria = < 50 cc/24 hours
(30
cc/hr used as indicator = 720 cc/24 hours)
3. Tubular secretion: involves the transport of materials from the
peritubular capillary network surrounding the tubular system into the cells
lining the tubular lumen and into the tubular lumen for excretion.
What
is secreted? hydrogen, potassium,
ammonia
Filtration
Blood is delivered via the afferent
arteriole at approximately 60-75 mm Hg.
If the blood pressure is higher than all
opposing pressures, filtrate is pushed through the glomerular filtration
membrane (i.e. electrolytes, non-electrolytes, and water, trace albumin)
The glomerular
filtration membrane is composed of:
1. vascular
endothelial cells (which cant regenerate)
2. basement
membrane (full of glucose and protein = glycoprotein)
3. epithelial
cells (can regenerate)
Glomerulonephritis
(GN) (= inflammation of the glomerulus) - makes layer 1 (vascular endothelial cells)
leaky; cant come back; RBC casts (Types:
lupus nephritis, autoimmune glomerulonephritis, acute post-streptococcal
GN, chronic GN)
Diabetes
mellitus (nephropathy) - affects layer 2; DM adds more
sugar; widens the basement membrane
The
effects of hyperglycemia on the filtration apparatus:
a. dilate afferent arteriole
b. constrict efferent arteriole
c. increase filtration pressure
d. microalbuminuria
Nephrotic
syndrome - makes layer 3 (epithelial cells) very
leaky; spilling lots of protein into tubules and thus into the urine; can
recover from this
Nephrosis
= 2.0 Gm/day
Nephrotic
syndrome > 3.5 Gm/day
If losing protein (albumin), fluids move
from circulation in tissue ---> edematous (with nephrosis, may have up to 80
lbs. of fluid in tissue).
Treatment: albumin
(to move fluid back into the blood vessels)
Lasix
(then get rid of fluid)
Causes: in kids (idiopathic; after bee
sting)
in
adults (multiple myeloma, DM, amyloidosis)
1+ 1,000 nephritic 3+ 3,000 nephrotic
2+ 2,000 nephritic 4+ > 4,000 nephrotic
Effects of protein in the diet:
increased
protein ---> increased risk of kidney damage (increases angiotensin II)
So,
decrease protein in diabetes mellitus
Tubular
System:
PCT (proximal convoluted tubule), DCT (distal convoluted tubule), CD
(collecting duct) and the loop of Henle
Proximal convoluted tubule:
65-80% of bulk (water, lytes, non-lytes)
reabsorbed
100% reabsorbed: potassium, glucose, amino acid
If blood sugar > 180, what you push
across the membrane will not all come back (renal threshold = 180)
With chronic renal insufficiency: can get sugar in urine
Creatinine: filtered, but not secreted or reabsorbed
Creatinine
clearance:
very sensitive/good test of filtration; decreases with decreased kidney
function
Serum
creatinine: doesnt show anything until
50-70% reduction in filtration
Creatinine
clearance: will decrease with even 10%
reduction in function
Note: Tagamet stops all secretion of creatinine;
Serum creatinine can increase 20%
when on Tagamet.
Normally: most creatinine goes right into the toilet,
but a very small amount is secreted into the tubules. If on Tagamet, all this
is stopped, leading to the 20% increase in creatinine.
(BUN:
increases in kidney dysfunction, but also in GI bleed, liver dysfunction,
diet high in red meat, dehydration.
Normal BUN to creatinine ratio is 20:1)
ATN:
can result from inhaling carbon tetrachloride and drinking alcohol
Loop of Henle:
Function is to maintain a high solute
concentration in the medullary interstitium
This allows for the variation in the amount
of water and electrolytes that are reabsorbed from the distal convoluted tubule
and collecting duct in response to ADH
300 mOsm is isotonic (same as serum)
---> concentrate urine by active pump of Na and Cl out, leaving water in the
tubules.
Result is hypotonic in tubule (150 mOsm)
and hypertonic in tissue (800 mOsm)
In the collecting duct, the ADH
receptors are open. Water moves from the
tubule into the tissues.
Clinical implications:
1. Function
of loop diuretics (Lasix, Bumex, Dimedex):
pump inhibitors (inhibit pumping
of Na and Cl into the tissues)
2. Loss
of ability to concentrate urine is the first to go
3. Major
concentration of urine occurs at night; thus, nocturia is a significant symptom
If
disease in interstitium, Na and Cl dont move out, cant concentrate urine.
Check
specific gravity: normally 1.025 in AM
(= 800 mOsm). If 1.010 (= 300 mOsm), not concentrating, so will have
nocturia. S.G. becomes fixed in renal
failure regardless of fluid volume (usually about 1.010)
Note: Nocturia can also be due to BPH, DM, CHF
(fluid from tissue moves into circulation at night when lying down)
Distal tubule and collecting duct: reabsorption and secretion under the
influence of aldosterone and ADH:
-
aldosterone for the net secretion of K+ and reabsorption of water and Na+
-
ADH for the reabsorption of free water
Acid-Base Balance
The body produces acids in excess of
40-60 mEq/day. In order to get rid of
the excess, the body saves a base (HCO3) and excretes an acid (H+). If the kidney does not get rid of excess H+,
things back up ---> acidosis
Pathophysiology: Prototypical health problems of the adult
Urinary
Tract Obstruction
Kidney stones
Affects male:female 4:1
75% of stones are calcium oxalate
S/Sx:
hematuria, pain in flank to scrotum or to labia majora (Remember: embryologically: ovaries and testicles originally develop near
the kidney)
Urinary
Tract Infection
At risk:
premature newborns, prepubertal children, sexually active young women,
diaphragm spermatocide use, and elderly males and females
A UTI can occur anywhere along the urinary
tract, including the urethra, prostate, bladder, ureter, and kidney.
In elderly female, the health of the
urethra is dependent on estrogen (keeps bacteria from moving up urethra)
If estrogen is lacking, UTI develops
Solution:
estrogen replacement therapy
Acute Pyelonephritis:
Definition:
an infection of the renal pelvis and interstitium
Causes:
kidney stones, vesicoureteral
reflux, pregnancy, neurogenic bladder, instrumentation, female sexual
trauma
S/Sx:
usually acute, with fever, chills, flank or groin pain, frequency,
dysuria, and costovertebral tenderness.
** Children and older adults may have
nonspecific symptoms such as fever and malaise
Treatment:
antibiotic therapy (14 days)
Chronic Pyelonephritis
Definition:
a persistent or recurrent autoimmune infection of the kidney with
inflammation and scarring of the kidney
Note:
urine may contain only a few white cells and bacteria
More likely to occur in patients who have
renal infections associated with some type of obstructive pathologic condition
such as renal stones and vesicoureteral reflux.
Chronic urinary tract obstruction prevents
elimination of bacteria in the normal flow of urine, resulting in progressive
inflammation that causes fibrosis and scarring.
S/Sx:
may include HTN, may have frequency, dysuria, and flank pain, but mild
and more vague.
Progression of the disease leads to renal
failure
Glomerular
Disorders
Glomerulonephritis
Definition:
an inflammation of the glomerulus that can be caused by a variety of
factors including immunologic abnormalities, effects of drugs or toxins,
vascular disorders, and systemic diseases
Several types:
Acute GN:
frequently associated with a
poststreptococcal infection, usually 7-10 days after a streptococcal infection of
the throat (5-10% incidence) or skin (25% incidence), commonly in children
S/Sx:
acute onset of hematuria, RBC casts, proteinuria, decreased GFR,
oliguria, edema, and HTN
Edema of acute GN tends to be around the
eyes but may involve dependent areas such as the feet and ankles
The thickening of the glomerular membrane
contributes to the decreased GFR.
Antibiotic therapy prevents the spread of
infection, but there is no specific treatment for the GN. Most individuals, especially children,
recover without significant loss of renal function or recurrence of the
disease.
Rapidly progressive glomerulonephritis
(RPGN)
Primarily affects adults in their 50s and
60s
May be idiopathic or associated with a
number of proliferative glomerular diseases, such as poststreptococcal GN and
Goodpasture syndrome (a disease associated with antibody formation against both
pulmonary capillary and glomerular basement membranes which occurs in men 20-30
years of age)
By the time RPGN is diagnosed, renal
insufficiency is apparent.
Typically, the glomerular injury is
accompanied by a rapid decline in glomerular function progressing to renal
failure in a few weeks or months.
Relatively poor prognosis. Dialysis or transplantation is required when
failure is irreversible
Chronic glomerulonephritis
Includes a variety of glomerular disease,
each with a progressive course leading to chronic renal failure
May occur with no history of renal disease
before the diagnosis, although several years of proteinuria and hematuria may
have preceded the diagnosis
Two major changes in the urine are
distinctive of glomerulonephritis:
1. hematuria
with RBC casts (urine is smoky brown-tinged, vs. pink/red if bleeding from lower in the urinary tract)
2. proteinuria
exceeding 3-5 g/day, with albumin as the major protein
Renal
Failure
renal insufficiency
= a decline in renal function to about 25% of normal or a GFR of 25-30
ml/min. Levels of serum creatinine and
urea are mildly elevated.
renal failure
often refers to significant loss of renal function
end-stage renal failure
= when less than 10% of renal function remains
Acute renal failure (ARF)
Definition:
an abrupt reduction in renal function with elevation of BUN and plasma
creatinine levels
usually associated with oliguria (urine
output of <30 ml/hr or < 400 ml/24 hours
Usually reversible if diagnosed and treated
early
Prerenal ARF: caused by impaired renal blood flow --->
decreased filtration pressure ---> decreased GFR (Due to renal vasoconstriction,
hypotension, hypovolemia, hemorrhage, inadequate cardiac output)
Intrarenal ARF: causes include acute tubular necrosis,
glomerulopathies, malignant HTN, coagulation defects
Postrenal ARF: usually occurs with
urinary tract obstruction that affects the kidneys bilaterally (e.g., bladder outlet obstruction, prostatic
hypertrophy, or bilateral ureteral obstruction). Can occur after diagnostic catheterization of
the ureters, a procedure which may cause edema of the tubular lumen.
Stage of renal failure: oliguria, diuresis, and recovery
Return to normal status may take from 3-12
months, with 30% of individuals not having full recovery of a normal GFR or
tubular function
Treatment:
prevention through maintenance of fluid volume before and after surgery
or diagnostic procedures; correct fluid and electrolyte disturbances, treat
infections, maintain nutrition.
Chronic Renal Failure (CRF)
Definition:
progressive and irreversible loss of renal function
S/Sx: = uremia,
the sx. caused by decline in renal function with the accumulation of toxins in
the plasma: anorexia, N, V, diarrhea,
weight loss, pruritus, edema, neurologic changes
Treatment:
dietary management, sodium and fluid restriction (urine output + 500 cc
insensible water loss), potassium restriction, erythropoietin
Hematuria
Normal urine contains few or no RBCs
If large numbers of RBCs are present, this
is known as hematuria and the
sediment may be red.
An alkaline or hypotonic urine causes lysis
of red cells, however, so that the cells will not be seen.
Urine then will be positive for hemoglobin,
and the specific gravity will be elevated.
Hematuria can occur with the administration
of anticoagulants and with several renal diseases.
Urinary incontinence
total
incontinence:
inability to store any urine; indicates an anatomic or functional
absence of urinary sphincters (myelomeningocele)or a bypassing of urinary
sphincters (vesicovaginal fistula)
overflow
incontinence:
frequent dribbling that relieves a constantly full bladder; occurs when
urinary outlet is obstructed
urge
incontinence:
sudden and uncontrollable need to void that cannot be suppressed;
suggests bladder irritation
precipitate
voiding:
voiding without a preceding urge to void; suggests neurologic origin
stress
incontinence:
uncontrollable voiding that occurs when intravesical pressure
momentarily excess intravesical resistance (during laughing, sneezing, or
coughing)
paradoxic
incontinence:
incontinence in spite of normal voiding; suggests an ectopic ureteral
orifice outside the urinary sphincter mechanism
Pathophysiology: Protypical health problems of the pediatric
patient
Structural alterations
hypospadias: a congenital condition in which the urethral
meatus is located on the ventral side or undersurface of the penis
epispadias: the urethral opening is on the dorsal surface
of the penis (in females, a cleft along the ventral urethra usually extends to
the bladder neck)
exstrophy
of the bladder:
an extensive congenital anomaly in which the lower urinary tract is
exposed directly to the surface of the body
hypoplastic
kidneys: very small normal kidneys
renal
dysplasia:
results from abnormal differentiation of the renal tissues
renal
agenesis:
failure of a kidney to grow or develop
Glomerular alterations
Nephrotic
syndrome:
a symptom complex characterized by proteinuria, hypoproteinemia,
hyperlipidemia, and edema (especially, periorbital). In children, the kidney is usually the only
or principal organ involved.
Treatment: activity as tolerated;
low-sodium, well-balanced diet; glucocorticosteroids (prednisone), diuretics
(Lasix), and immunosuppressive agents (cytoxan, Imuran); paracentesis (for
ascites); and skin care. Most have
complete remission.
Glomerulonephritis: includes a number of renal disorders in which
proliferation and inflammation of the glomeruli are secondary to an immune
mechanism (includes poststreptococcal glomerulonephritis and IgA nephropathy)
hemolytic
uremic syndrome:
an acute disorder characterized by hemolytic anemia originating in the
microcirculation, thrombocytopenia, and acute renal failure.
Obstructive alterations
urinary
tract infections:
rare in newborns and are usually caused by bacteria from the bloodstream
settling in the urinary tract. Most
common in 7-11 year old girls
vesicoureteral
reflux:
retrograde flow of bladder urine into the ureters; allows infected urine
from the bladder to be repeatedly swept up into the kidneys.
Wilms tumor
Definition:
an embryonal tumor of the kidney
Also known as nephroblastoma
Most common childhood cancer of the urinary
tract: 400 cases/year in the
Slightly more common in black children than
in white children
Child usually appears healthy; parent may
discover abdominal swelling.
HTN may be present due to either
encroachment by the tumor on the blood supply or secretion of renin by the
tumor
Dx. with ultrasound and surgical biopsy
Treatment:
surgical exploration and resection, radiation therapy, chemotherapy
Overall cure rate is 90% for stage
I-III. Poor prognosis if metastases
present.
Enuresis
Definition:
the involuntary passage of urine by a child who is beyond the age when
voluntary bladder control should have been acquired (usually before age 4)
Primary
enuresis:
a condition in which the child has never been continent
Secondary
(acquired) enuresis:
occurs when a child who has experienced a period of dryness of at least
3-6 months after toilet training becomes incontinent again. May be diurnal (daytime), nocturnal, or a combination
of both
Causes:
UTI, neurologic disturbances, congenital defects of the meatus, urethra,
and bladder neck, allergies, DM, maturational lag, genetic factors, deep sleep,
psychosocial problems.