The percentages of body water contained in various fluid compartments add up to total body water (TBW). This water makes up a significant fraction of the human body, both by weight and by volume. Ensuring the right amount of body water is part of fluid balance, an aspect of homeostasis. The extracellular fluid (ECF) includes all fluids outside the cells. This fluid can be divided into three fluid departments: interstitial (in the tissue spaces) fluid, blood plasma and lymph, and specialised compartments called transcellular fluid. The extracellular fluid surrounds all the cells in the body and is in equilibrium with the intracellular fluid. So, its composition must remain fairly constant even though substances are passing into and out of the cells. The interstitial fluid, though called a fluid, is in a reality a gel-like composition made up of: water, proteoglycan molecules and collagen. The extracellular fluid constitutes 40% of total body water, with intracellular fluid making up the remaining 60%. It is relatively rich in glucose.

Proteinuria refers to an increased amount of protein excretion in urine, which should be greater than 100mg/m2 per day on a single spot urine collection. The limit is even more relaxed for infants and neonates. Proteinuria is a prominent manifestation of cystinosis, acute tubular necrosis, Fanconi syndrome, and celiac disease. Landau-Kleffner syndrome is a rare childhood convulsive disorder, associated with acquired aphasia and auditory verbal agnosia.

Progressive vomiting due to pyloric stenosis leads to hypochloraemic, hypokalaemic, metabolic alkalosis.

The most commonly requested biochemistry tests for renal function are the urea and electrolytes. They supply important information when it comes to homeostasis and excretion. Glomerular filtration rate is also the essential standard marker of kidney health and is assessed by checking the creatinine levels. In this case as the child has lost fluids and electrolytes, this test will indicate the extent of the loss and allow for more appropriate replacement.

Constipation is often associated with nocturnal enuresis in children. The palpable mass is the impacted stool. The decreased appetite is common in those with constipation.

Because the medical history included tonsillitis followed by haematuria and hypertension, there is a strong suspicion of a case of post-streptococcal glomerulonephritis (PSGN). Patients with PSGN usually have serological findings showing depressed serum haemolytic component CH50 and serum concentrations of C3. Sometimes depressed C4 levels are also apparent, but not always, therefore, the answer to this question is: depressed CH50 level.

Hypospadias is an abnormality of anterior urethral and penile development. The urethral opening is located on the ventral aspect of the penis proximal to the tip of the glans penis, which, in this condition, is open. The urethral opening may be located as proximal as in the scrotum or perineum. The penis may also have associated ventral shortening and curvature, called chordee, with more proximal urethral defects.

According to WHO, the treatment protocol in severely dehydrated children, is to infuse a bolus of isotonic crystalloid over 20-30 min at 30ml/kg to children less than 12 months of age followed by giving the remaining fluid over 5 hours for infants. Reference: World Health Organisation, the treatment of diarrhoea, a manual for physical and senior health workers.

Vesicoureteric reflex (VUR) is described as the retrograde flow of urine from the bladder into the ureter due to an incompetent uterovesical junction. In primary VUR the lower urinary tract functions normally, while secondary VUR is associated with a poorly functioning lower urinary tract. The incidence of VUR is highest in new-born girls. They can present with hydronephrosis, or urinary tract infections.

The most probable diagnosis for this patient would be a duplex kidney with an ectopic ureter inserting below the bladder neck.

Rationale:
The Weigert-Myer law states that the upper moiety ureter inserts inferior and medial to the lower moiety ureter.

Other options:
– Horseshoe kidney would display as a single pelvic kidney on an ultrasound scan.
– Ureterocele would be a cystic lesion within the bladder or may prolapse at birth.
– Continence should not be affected by polycystic kidney disease.
– The overactive bladder would cause frequency and urgency, neither of which is mentioned in the history.

The boy is most probably a type 1 diabetic patient. Such a condition can affect the behaviour and psychological state of a young child reflected in their behaviour. The parents should seek the help of a clinical psychologist.

HUS syndrome occurs mostly in children after some days of bloody diarrhoea. Damaged red blood cells also damage the kidney filtering unit and lead to sudden renal failure.

Based on the presented clinical scenario, the most probable diagnosis for the patient would be testicular torsion.

Rationale:
The gubernaculum is the structure responsible for aiding the descent of the testicles from the abdomen into the scrotum. The processus vaginalis precedes the descent of the testes and then undergoes closure.
Abnormalities such as the persistence of a patent processus vaginalis, known as bell clapper deformity, predispose to testicular torsion.

Other options:
– Varicocele: Nutcracker syndrome occurs where the left renal vein becomes compressed in between the superior mesenteric artery and the aorta. Since the left gonadal vein drains into the left renal vein, this results in a varicocele.
– Epididymitis and mumps orchitis are differentials for acute testicular pain but are not due to a defect in the processus vaginalis.
– An incarcerated inguinal hernia presents mainly with signs of bowel obstruction which are not mentioned in the clinical scenario.

The descent of testes:
– Until the end of foetal life, the testicles are located within the abdominal cavity.
– They are initially located on the posterior abdominal wall on a level with the upper lumbar vertebrae (L2).
– Attached to the inferior aspect of the testis is the gubernaculum testis which extends caudally to the inguinal region, through the canal and down to the superficial skin.
– It is interesting to note that both the testis and the gubernaculum are extra-peritoneal.
– As the foetus grows, the gubernaculum becomes progressively shorter. It carries the peritoneum of the anterior abdominal wall (the processus vaginalis). As the processus vaginalis descends the testis is guided by the gubernaculum down the posterior abdominal wall and the back of the processus vaginalis into the scrotum.
– By the third month of foetal life the testes are located in the iliac fossae, by the seventh they lie at the level of the deep inguinal ring.

Usually, the processus vaginalis closes after birth but may persist predisposing to indirect hernias.
On the other hand, a partial closure may result in the development of cysts on the cord.

Fanconi tubular syndrome is characterised by malabsorption of various electrolytes and substances commonly absorbed by the proximal tubule. Hypokalaemia, hypophosphatemia, and hyperchloremic metabolic acidosis is usually present. Also, urinalysis reveals an increased fractional excretion of glucose.

Gitelman syndrome is a kidney disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.

The signs and symptoms of Gitelman syndrome usually appear in late childhood or adolescence. Common features of this condition include painful muscle spasms (tetany), muscle weakness or cramping, dizziness, and salt craving. Also common is a tingling or prickly sensation in the skin (paraesthesia), most often affecting the face. Some individuals with Gitelman syndrome experience excessive tiredness (fatigue), low blood pressure, and a painful joint condition called chondrocalcinosis. Studies suggest that Gitelman syndrome may also increase the risk of a potentially dangerous abnormal heart rhythm called ventricular arrhythmia.

Fanconi syndrome is a rare disorder characterized by defective proximal renal tubular reabsorption, which leads to excessive excretion of potassium, phosphate, uric acid, bicarbonates, glucose, and certain amino acids in the urine. Loss of potassium in the urine leads to hypokalaemia, while the loss of phosphate may lead to hypophosphatemic rickets. The overall impact is the failure to thrive and growth retardation.

Nephrogenic Diabetes Insipidus is an acquired or hereditary condition that affects the water balance. It presents with polyuria and polydipsia, leading commonly to dehydration.

E. coli accounts for the majority of UTI’s in children. If this child responds well to treatment and has no recurrence of his symptoms, then no form of imaging is required, as per NICE advice for children aged 6 months to 3 years. Had the child been less than 6 months of age, then a USS at 6 weeks would be necessary.

Other options:
– Pseudomonas causes atypical UTI. This warrants ultrasonography within the acute illness phase as it may reflect an underlying pathology and DMSA at 4-6 months.
– Recurrent UTI is defined as two or more episodes of pyelonephritis OR 1 pyelonephritis and one cystitis OR 3 or more cystitis. It requires USS at six weeks and DMSA at 4-6 months.
– Septicaemia is a sign of an atypical UTI. This requires USS within the acute illness as it may reflect an underlying pathology and DMSA at 4-6 months.
– Unwell 48hrs post antibiotics is a sign of an atypical UTI. This requires USS within the acute illness as may reflect underlying pathology and DMSA at 4-6 months.

The presentation is suggestive of nephrotic syndrome. A trial of corticosteroids is the first step in treatment of idiopathic nephrotic syndrome. Diuretics are useful in managing symptomatic oedema. Cyclosporin and cyclophosphamide are indicated in frequently relapsing and steroid dependant disease.

Minimal change glomerulonephritis presents with mild or benign urinalysis findings. However, proteinuria together with the presence of oval fat bodies are typical.
Minimal change glomerulonephritis (nephropathy) accounts for most cases of childhood nephrotic syndrome and 20-25% of adult nephrotic syndrome.

Henoch-Schonlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of bleeding underneath the skin), often with joint pain and abdominal pain. It is an acute immunoglobulin A (IgA)-mediated disorder. The tetrad of purpura, arthritis, kidney inflammation, and abdominal pain is often observed.

Based on the clinical presentation, the child probably has orthostatic proteinuria.

Orthostatic proteinuria occurs when the kidneys can conserve urine when the patient is recumbent, such as sleeping at night, but leak protein with standing or in exercise.
This results in early morning urine being negative for protein but late in the day urine being positive. It is mostly seen in tall thin adolescents and is benign.

Other options:
– Alport’s syndrome is a hereditary condition associated with haematuria and deafness.
– Urinary tract infections can cause proteinuria, but leucocyte esterase and nitrites would also be expected in a child of this age.
– Nephritic syndrome can be associated with proteinuria, but haematuria would also be present.
– In nephrotic syndrome, proteinuria would be present on all occasions and associated with oedema.

Renal stones < 5mm generally pass spontaneously with adequate fluid intake. Stones 5mm-10mm with pain not resolving, require medical expulsive therapy with Nifedipine or Tamsulosin. For stones larger than 10mm, ESWL or Ureteroscopy is indicated. For stones as big as 2cm, percutaneous nephrolithotomy should be applied.

ADH primarily acts on the collecting ducts.

Other options:
– The juxtaglomerular apparatus is the site of renin production.
– The proximal tubule conducts isosmotic reabsorption of about 60% of sodium chloride and volume. Most of the glucose, amino acids, potassium and phosphate are absorbed here.
– The loop of Henle is the site of 25% of sodium reabsorption. Active Chloride transport provides the basis for the counter current multiplier aiding urinary concentration.
– The distal convoluted tubule is impermeable to water and acts via active sodium chloride absorption to dilute urine.

The most probable diagnosis for this patient is bilateral retractile testes. This a normal phenomenon in some pre-pubertal boys.

Rationale:
Testicular descent can continue until about 3-months of age. The pre-pubertal testis is small enough that with activation of the cremasteric reflex, they can enter the inguinal canal.
This in itself is a normal finding providing the testis can be brought into the scrotum without tension and does not require surgical correction. With time the testis will lie within the scrotum.

Orchidopexy for true undescended testis can be performed from 6-months of age. It is also warranted if the testes remain undescended or intra-abdominally leading to infertility.

Other options:
– An ascending testis is one, typically, following hernia or orchidopexy surgery that was in the testis but with time is within the inguinal canal and cannot be brought into the scrotum. Orchidopexy is required for this.
– No surgery is required as when the testis enlarges with puberty it will remain within the scrotum.
– The testes can be brought into the scrotum. Therefore they are not undescended.
– The testes are retractile not ascending; ascending testis cannot be brought into the scrotum and would require orchidopexy.

The cells in the testes that secrete testosterone are the Leydig cells.

Other cells in testes include:
– Spermatogonia: These are undifferentiated male germ cells which undergo spermatogenesis in the seminiferous tubules of the testes.
– Sertoli cells: They are a part of the seminiferous tubule of the testes, cells are activated by FSH and nourish developing sperm cells.
– Myoid: They are squamous contractile cells which generate peristaltic waves, they surround the basement membrane of testes.
– Fibroblasts: Cells which synthesise collagen and the extracellular matrix.

Coverings of the spermatic cord:
Spermatic cord is covered by three concentric layers of fasciae, derived from the layers the of anterior abdominal wall. Developmentally, each covering is acquired as the processus vaginalis descends into the scrotum through the layers of the abdominal wall. The layers are:

External spermatic fascia: It is derived from the external oblique muscle. It attaches to the margins of superficial inguinal ring.
Cremasteric fascia: It is derived from the internal oblique muscle. It covers the cremaster muscle.
Internal spermatic fascia: It is derived from the fascia transversalis (fascia covering the transversus abdominis muscle). It is attached to the margins of the deep inguinal ring.

This patient has pulmonary renal syndrome which is most commonly due to an ANCA positive vasculitis. The history of recurrent epistaxis makes Wegener’s granulomatosis the most probable diagnosis. Wegener’s granulomatosis, microscopic polyangiitis, and idiopathic pauci-immune necrotizing crescentic glomerulonephritis (NCGN) are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against either proteinase 3 (anti-PR3) or myeloperoxidase (anti-MPO).

Urine culture confirms a diagnosis of a UTI. A kidney ultrasound will be the next best investigation because it will help us to visualise the bladder, kidneys, and ureters to rule out any congenital obstruction in the urinary tract that might be the actual cause of infection in this 2-month old girl.

The patient shows features of neurofibromatosis. The most likely cause for hypertension in this patient would be renal artery stenosis.

Note:
Neurofibromatosis is an inherited autosomal dominant disorder which could have affected this girl’s father, and she appears to have the classic skin lesions.
A renal bruit might be heard in these patients.
Polycystic kidney disease can occur in association with tuberous sclerosis, which also has skin lesions associated (different from those described in this patient).
Most causes of hypertension in childhood have underlying renal causes, and a renal ultrasound with doppler is the first-line investigation of choice. Even if this is normal, further imaging would be indicated here, for example, isotope renal scans and angiography.