Unit 3 - Chapter 40 Alterations of renal and urinary tract in children

Question 1

Wilms tumor 1 gene and WNT signaling

Answer 1

• provides instructions for making a protein that is necessary for the development of the kidneys and gonads (ovaries in females and testes in males) before birth. After birth, WT1 protein activity is limited to a structure known as the glomerulus, which filters blood through the kidneys. The WT1 protein plays a role in cell growth, the process by which cells mature to perform specific functions (differentiation), and the self-destruction of cells (apoptosis). To carry out these functions, the WT1 protein regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, the WT1 protein is called a transcription factor.

============
* Acting as intercellular signals, Wnt proteins regulate the proliferation of cells. Wnt signals are active in numerous contexts, initially in early development and later during the growth and maintenance of various tissues. In comparison to other growth factors, Wnt signals have several unique properties, including a short range of action. Thereby, Wnts predominantly mediate signaling locally, between neighboring cells. In addition, Wnt signals give shape to tissues as cells are proliferating. This is a consequence of the ability of Wnt signaling to confer polarity and asymmetry to cells. Wnt proteins are highly conserved in evolution and are active in every branch of the animal kingdom.

========

• specifically – kidney development, growth, and differentiation

Question 2

Kidney develops from what three set of structures?

Answer 2

1. pronephros (nonfunctional end of embryonic period)
2. mesonephros (nonfunctional)
3. metanephros (funcitonal kidney)

Question 3

What happens w/ full term birth?

Answer 3

• all nephrons are present
• number does not inc w/ maturation BUT mainly in wt and fx

Question 4

When does urine formation begin?

Answer 4

• 3rd gestational month
• contributes to amniotic fluid

Question 5

Infant and their chemical safety margin

Answer 5

• generally narrow margin @ infant age d/t (difference between the usual effective dose and the dose that causes severe or life-threatening side effects)

1. high hydrogen ion concentration [The dilute urine is accentuated by a low rate of urea excretion, which is necessary to establish the concentration gradient in the medulla. Urea excretion is low primarily because infants are in a high anabolic state and use their protein for growth ==> acid load from high protein?]
2. limited ability to regulate internal environment
3. lowered osmotic pressure (differences in solutes compared to hydrostatic pressure – water force + gravity)

Question 6

What can rapidly l/t severe acidosis and fluid imbalance in infants?

Answer 6

• diarrhea, infection, fasting, or feeding alterations

Question 7

How does kidney develop?

Answer 7

• from medulla to cortex
• blood flow to medullary nephrons limited in infancy ==> l/t limited urine-concentrating capacity

Question 8

Horseshoe kidney

Answer 8

• single U-shaped kidney that dvelops from fusion of kidneys as they descend from the midline
• kidney can be asymptomatic or associated w/ hydronephrosis (stretched and swollen as the result of a build-up of urine inside them), stone formation, or infection
• causing obstruction, vesicoureteral reflux (urine backflow)
• surgery if further complicated

Question 9

Hypospadias vs epispadias

Answer 9

• Hypospadias - urethral meatus located on undersurface of penis
• Epispadias - urethral opening located on dorsal surface of penis (above)
• both are congenital disorders
• tx via surgery (6-12 months) // severe cases - while in utero!

Question 10

Exstrophy of the bladder

Answer 10

• congenital malformation
• pubic bones are separated
• lower portion of abdominal wall and anterior wall of bladder missing
• back wall of bladder is exposed (anterior aspect not fully developed) + including urethra
• surgery performed 1st weeks of life => staged surgeries required over months/years

Question 11

Ureteropelvic junction obstruction

Answer 11

• blockage where renal pelvis (where medulla empties out) joins the ureter often caused by smooth muscle or urothelial malformation or scarring l/t hydronephrosis
• essentially pinching of ureter starting end!
• typically open surgery and cut out area of scarring + reconnect the ureter to the kidney

Question 12

Bladder outlet obstruction

Answer 12

caused by urethral valves (additional growths in urethra) or polyps

Question 13

Dysplatic kidney

Answer 13

• d/t abnormal differentiation of renal tissues

Question 14

Hypoplastic kidney

Answer 14

very small, but normal kidney

Question 15

Renal agenesis

Answer 15

• failure of a kidney to grow or develop
• unilateral or bilateral
• can be isolated entity or association with other d/o

Question 16

Glomerulonephritis

Answer 16

• inflammation of glomeruli secondary to immune mechanisms
• caused by hematuria, edema, and HTN
• Poststreptococcal glomerulonephritis may after infection, especially of the upper respiratory tract

Question 17

IgA nephropathy

Answer 17

• deposit of IgA immunoglobulins and other immune products in the mesangium attached to glomeruli capillaries
• most common type of childhood glomerulonephritis

Question 18

Henoch-schonlein nephritis

Answer 18

• immune-mediated IgA vasculitis that affects glomerular blood vessels causing inflammation and damage to the vessel wall
• also involves small vessels in skin and gut
• Palpable purpura, arthritis, and abdominal gut
• some developed hematuria w/ mild or no proteinuria (within 4 weeks of disease onset)
• can l/t development interstitial fibrosis and crescent formation from subepithelial immune deposits along glmeruli increase risk of chronic renal failure
• most children recover supportive care, although some progres to kidney failure

Question 19

Hemolytic uremeic syndrome

Answer 19

• actue d/o
• hemolytic (destruction of RBC) anemia
• acute renal failure
• thromobocytopenia
• can be associated with e coli verotoxin
• other bacterial and viral agents; other exposures include animals, unpasteurized beverages, contaminated meat/vegetables + cancer/chemotherapeutic agents

==========
* verotoxin (shiga toxin) from e cooli absorbed from intestine into blood
* binds to polymorphonuclear leukocytes => transport to kidney causing multiple effects (lysis of glomerular capillary endothelial cells, separation of endothelial cells from basement membrane, activation/aggregation of platelets + Fibrin clots)
* causing glomerular arterioles to become swollen and occluded with platelets and fibrin clots
* decreased GFR, damaged glomerular membrane => hematuria and proteinuria; oliguria with renal failure happens up to 50% of children
* narrowed vessels damage RBC’s => these damaged RBC’s (burr cells, helmets cells, and fragment RBCs) get removed by spleen causing acute hemolytic anemia
* Fibrinolysis => dissolution of a clot => acts on precipitated fibrin to split causing it to form in serum and urine
* clustering of platelets wtihin damaged vessels + damage and removal of platelets l/t thrombocytopenia (fribrin-rich thrombi present through microcirculation)
* invovling also brain, liver, heart, and intestines
* D+ HUS (shiga toxin producing e coli) preceded by diarrhea
* Atypical HUS (aHUS) => Or D- HUS; dysregualtion of alternative complement pathway is noted
* Familial aHUS is rare
* D+ HUS occurs after 1-2 weeks after GI illness with sx free 1-5 day period

////
sx
* pallor, bruising, purpura, irritability, and oliguria
* slight fever, anorexia, vomting, diarrhea, abdominal pain, mild jaundice, circulatory overload
* seizure and lethargy (CNS)
* Renal failure within 2 days to 2 weeks of onset => metabolic acidosis, uremia, hyperkalemia, and HTN

Question 20

Nephrotic syndrome

Answer 20

symptom complex
* proteinuria
* hypoalbuminemia
* hyperlipidemia
* edema
* disturbance in the glomerular basement membrane l/t increased permeability to protein
* most common form — Minimal change neuropathy disease is the most common cause of nephrotic syndrome in children. It is also seen in adults with nephrotic syndrome, but is less common. The cause is unknown, but the disease may occur after or be related to: Allergic reactions. Use of non-steroidal anti-inflammatory drugs (NSAIDs)
1) disorder where there is damage to glomeruli (the damage cannot be seen under a regular microscope)

Question 21

Renal injury in children?

Answer 21

• acute or chronic renal injury is rare
• most common is prerenal acute renal failure r/t dehydration, sepsis or hemorrhage
• prerenal means… occurs due to poor perfusion of nephrons, which in turn leads to a decrease in the GFR. Fundamentally, it is related to an imbalance in the delivery of nutrition and oxygen to the nephrons during periods of increased energy demand.

Question 22

Wilms tumor

Answer 22

• embryonal tumor of kidney that presents between birth and 5 y/o as an inherited (1-2%) or sporadic form
• sometimes in older children and rarely in adults
• chromosomal deletion of WT1 (wilms tumor suppressor gene) or deletion of WT2 (2nd wilms tumor suppression gene), loss of heterozygosity of 16q and 1p, and inactivation of WTX gene
• Treatment may include surgical resection, chemotherapy, and radiation therapy.
• This includes: dactinomycin (actinomycin D) and vincristine w/ or w/o doxorubicin ==> chemotherapy

sx ///
1) painless palpable abdominal mass
2) can have pain, hematuria, fever, anorexia, vomting
3) HTN may occur

diagnose
* Abdominal ultrasonography, CT, or MRI

Question 23

Urinary tract infection

Answer 23

• d/t general sepsis in the newborn but usually caused by bacteria ascending the urethra in older children
• cystitis => only bladder
• infection can go up to kidneys in pyelonephritis
• Urinary tract anomalies…? may require surgical correction to prevent recurrent infections

Question 24

Vesicoureteral reflux

Answer 24

• retrograde flow of bladder urine into the kidney and/or ureters
• cause of bladder + kidney infections in children
• unilateral or bilateral
• congential anomalous develop of the utererovescial junction (incomplete intramural ureteral tunnel l/t failure of normal flap valve at this junction causing reflux of bladder urine into the ureter and renal pelvis)
• reflux can occur with a ordinary one as well if bladder pressure increases d/t bladder outlet obstruction or dysfunctional voiding (infrequeny, constipation or both)
• ultimately, can l/t renal scarring => causing HTN and renal dysfunction

sx ///
1) fetal hydronephrosis or febrile UTI
2) fever, ab or flank pain, dysuria, frequency, urgency, wetting, or rarely hematuria

tx ///
* mild to moderate vesicoureteral reflux => often resolves spontaneously over months to several years
* for severe and recurrent: prophylatic antibiotics (trimethoprime [primsol]/sulfamethoxazole [Bactrim DS]) at bedtime + nitrofuratoin [macrobid] at dinner + cephalexin [keflex] BID
* additionally, anticholinergic (oxybutynin, solifenacin succinate)
* rarely bulking agent, bladder augmentation, ureteral reimplantation

Question 25

Urinary incontinence

Answer 25

• involuntary passage of urine beyond the age when normal continence should have occurred
• can occur during day (incontinence) or night (enuresis)