Introduction to Hemolytic-Uremic Syndrome.

Hemolytic-uremic syndrome (HUS), first described in 1955, is a heterogeneous syndrome characterized by a triad of microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. Initially thought to be a sporadic process, it is now recognized as the most common cause of acute renal failure in children.

Pathogenesis:
In D+ HUS (post diarrheal hemolytic uremic syndrome), with Shiga toxin-producing E. coli O157:H7 infection, the toxin binds, invades, and causes destruction of colonic epithelial cells, resulting in bloody diarrhea. Presumably because of the inflamed colon allowing transmural absorption, the toxin then enters the blood circulation. There the toxin binds to a glycolipid receptor known as globotriaosylceramide (Gb3), which results in endocytosis of the toxin usually within renal glomerular endothelial cells, and at times, other target organs. The expression of Gb3 receptors appears to be higher in infants and young children, which may in part explain the age-related propensity for developing HUS. Older children and adults have lower numbers of these receptors but may develop HUS whenever the combined effect of lipopolysaccharide and cytokines upregulate the expression of these Gb3 receptors.

Clinical Features:
With STEC (Shiga toxin producing E coli) infection, the incubation period is typically 3 to 4 days after exposure (range, 1 to 14 days).

Imaging For UTI in Children

The first goal of imaging the urinary tract is to discover abnormalities that either may be risk factors for UTI or may preclude prompt response to therapy. These risk factors include vesicoureteral reflux or voiding dysfunction, and factors that complicate therapy include partial ureteropelvic junction obstruction or cystic kidney disease. The second goal of imaging is to monitor renal growth and detect scarring.

Determining which children to evaluate, which tests are most appropriate, and when to obtain studies is critical to develop a rational and consistent approach to this controversial component of UTI.

For a long time, majority opinion favored imaging evaluation of the upper and lower urinary tract in every child following a well-documented first UTI.
(1) All patients with documented UTI should have ultrasound to assess integrity of the urinary tract;
(2) VCUG should be obtained in all patients less than 3 years of age and all patients with or suspected of having pyelonephritis;
(3) No further studies if ultrasound is normal in children older than 3 years or with minimal symptoms at presentation.

There are several reasons for routinely imaging infants and young children with UTI:
(1) a high incidence of VUR is found in this age group, approaching 35 to 50% (70% in children <1 year);
(2) renal scarring following infection is most likely to occur in the first 2 to 4 years of life; and
(3) symptoms are so vague that differentiation between upper and lower tract infection is usually impossible.
Once a decision to image the urinary tract has been reached, the choice of studies must be made.

Cystoscopy, although not an imaging study, directly visualizes the bladder, urethra, and ureteral orifices, but it is extremely invasive, generally requires general anesthesia in children, and offers little advantage over cystography in the evaluation of a child with UTI. Cystoscopy in girls with recurrent cystitis to diagnose any urethral stenosis,or a condition whose existence is seriously questioned, is not indicated.

The intravenous pyelogram (IVP) has largely been replaced by sonography.

Ultrasonography of the kidney and/or the bladder is simple and easy to carry out. Neither radiation exposure nor pain is involved, and it provides very accurate images and information on kidney size, shape, location, and texture . Echogenicity of the kidney may be altered with inflammation, either diffusely (as occurs in pyelonephritis) or focally (as is seen in acute lobar nephronia). Ultrasonography cannot assess renal function, reliably diagnose or exclude VUR, or demonstrate mild scars.

An Overview of Nephrotic Syndrome

Pediatric Nephrotic syndrome is defined by the presence of:

• nephrotic proteinuria > 1 g/m2/day,
• hypoproteinemia – albumin usually < 25 g/l, based on protein loss to urine,
• hypercholesterolemia – based on increased lipoprotein synthesis (caused by hypoproteinemia),
• edema – based on increased naturism resorption in tubules.

Nephrotic syndrome is a constellation of clinical findings that is the result of massive renal losses of protein. Thus, nephrotic syndrome is not a disease itself, but the manifestation of many different glomerular diseases.

Minimal Change DiseaseMinimal Change Disease (also known as lipoid nephrosis) is a disease of the kidney that causes nephrotic syndrome and usually affects children (peak incidence at 2–3 years of age).

Pathophysiology
Nephrotic syndrome is a nonspecific disorder in which thekidneys are damaged, causing them to leak large amounts of protein from the blood into the urine.

Kidneys affected by nephrotic syndrome have small pores in the podocytes, large enough to permit proteinuria (and subsequently hypoalbuminemia, because some of the protein albumin has gone from the blood to the urine.

NS is believed to have an immune pathogenesis. Evidence of the immune-mediated nature of NS is demonstrated by the fact that immunosuppressive agents, such as corticosteroids and alkylating agents, can result in remission of nephrotic syndrome.

Pathology of Edema in Nephrotic Syndrome
The classical explanation for edema formation is a decrease in plasma oncotic pressure, as a consequence of low serum albumin levels, causing an extravasation of plasma water into the interstitial space. The resulting contraction in plasma volume (PV) leads to stimulation of the renin-angiotensin-aldosterone axis and antidiuretic hormone. The resultant retention of sodium and water by the renal tubules contributes to the extension and maintenance of edema.

A more recent theory of edema formation posits that massive proteinuria leads to tubulointerstitial inflammation and release of local vasoconstrictors and inhibition of vasodilation. This leads to a reduction in single-nephron glomerular filtration rate and sodium and water retention.

Wilm’s Tumor- A Childhood Malignancy

Wilms tumor, or nephroblastoma, is the most common childhood abdominal malignancy.

Wilms’ tumor most often affects children ages 3 to 4 and becomes much less common after age 5. This tumor most often occurs in just one kidney, though it can sometimes be found in both kidneys at the same time.

Improvements in the diagnosis and treatment of Wilms’ tumor have improved the prognosis for children with this disease.

Pathology
Wilm’s tumor tends to be encapsulated and vascularized that do not cross the midline of the abdomen. In cases of metastasis it is usually to the lung. A rupture of Wilms’ tumor puts the patient at risk of hemorrhage and peritoneal dissemination of the tumor. In such cases, surgical intervention by a surgeon who is experienced in the removal of such a fragile tumor is imperative.

Pathologically, a triphasic nephroblastoma comprises three elements:

1. blastema
2. mesenchyme
3. epithelium

Wilms’ tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, fibrous tissue. The tumor is compressing the normal kidney parenchyma.

The mesenchymal component may include cells showing rhabdomyoid differentiation. The rhabdomyoid component may itself show features of malignancy.

Wilms’ tumors may be separated into 2 prognostic groups based on pathologic characteristics:

1. Favorable – Contains well developed components mentioned above
2. Anaplastic – Contains diffuse anaplasia (poorly developed cells)

Approach To A Child Presenting With Urinary Retention

Acute urinary retention is relatively infrequent in children. There are a variety of causes that are poorly defined in the literature, and they differ greatly from those seen most frequently in adults.

Urinary retention means an inability to void or unable to empty the bladder.

Taking the History
When a child presents with the complains of inability to void a detailed history is required in order to reach the diagnosis and then manage accordingly.

Ask:

1. If the patient is toilet trained?

2. Is patient constipated

3. Is there pain on urination or fever

4. Any history of trauma

5. Past history of UTI

6. Any history suggestive of sexual abuse

7. Any medications currently in use

Physical Examination
After a detailed history relevant physical examination is necessary that may include

• General Physical Appearance: the child may appear ill looking and uncomfortable.
• Abdomen: Tender , tense smooth suprapubic mass usually indicates a distended urinary bladder.
• Genitalia: Phimosis ( if uncircumcised) , meatal stenosis and erythema of perpuse or glans may represent acute balanoposthitis or erythema may indicate sexual abuse.
• Neurological examination: is needed to assess the sensation in the perineal area.

Introduction To Bartter Syndrome

Bartter syndrome is caused by an inborn autosomal recessive defect, in the Na-K-2Cl co transporter in the thick ascending limb of the loop of Henle, leading to NaCl and water wasting.

Clinical Symptoms
The patient presents with polyuria, polydipsia, episodes of dehydration, flattering growth and constipation. sometimes there may be maternal polyhydramnios with an affected fetus.

Pathophysiology
Since there is NaCl and water wasting the resultant ECF volume contraction causes secondary renin secretion and raised aldosterone levels, with avid Na and water reabsorption in the distal tubule and reciprocal K and H secretion into the urine. Imprtant to note is that blod pressure is normal. There is also increases renal prostaglandin E2 secretion.

The above changes produce the characteristic biochemical disturbance of hypochloraemic hpokalaemic alkalosis.

Diagnosis
Crucial to the diagnosis is the finding of inappropriately high levels of urinary Cl and Na- usually more than 20mmol/L ; urine Ca is normal or high.

Approach To A Child With Dysuria

A child may present with difficult or painful urination and it is important to ask a few questions that will help to reach an appropriate diagnosis.

Immediate Questions

1. When did the painful urination begin?
Trauma to the urinary tract must be ruled out if pain develops after an injury. Bicycle and straddle injuries commonly cause damage to the kidneys or urethra, leading to hematuria or dysuria or both. Consider behavioral problems , including attention seeking , if symptoms occur only at a particular time of day (e.g during school)

2. Where is the pain located?
An older child can locate the pain in the urethra, in the pelvis or in the abdomen. some children alos complain of a back pain. Pain originating from other organ system may be referred to the urethra. an intra abdominal abscess or a low lying inflamed appendix may produce complaints of dysuria. Dysuria associated with back pain is a common presentation of pyelonephritis. Renal stones in the pelvis, calyx, or ureter can cause abdominal or flank pain with radiation into the scrotum or vulva. Stones in the urethra or distal ureter Stones in the bladder are not associated with pain.