Case 31

Question 1

What are key findings from history in a 5 yo pt. with nephrotic syndrome?

Answer 1

Periorbital swelling, Recent upper respiratory infection, Fatigue, No fever, poor appetite, abdominal distention, negative past medical history

Question 2

What are key physical exam findings in a 5 yo pt. with nephrotic syndrome?

Answer 2

Weight gain, normal vitals, periorbital edema, negative cardiothoracic exam, ascites, pedal edema

Question 3

What is on the differential diagnosis for nephrotic syndrome?

Answer 3

First network:
-Sinusitis, allergy
-Congestive heart failure (CHF)
-Nephrotic syndrome
-Acue glomerulonephritis
-Hepatic failure
Second network: 
-Nephrotic syndrome
-CHF
-Acute glomerulonephritis
-Hepatic failure

Question 4

What are key findings from testing for nephrotic syndrome?

Answer 4

Proteinuria, Low albumin, Elevated lipids, Hyponatremia

Question 5

What is primary nephrotic syndrome?

Answer 5

Loss of protein due to specific kidney disease, such as:

• Minimal-change nephropathy
• Membranoproliferative glomerulonephritis
• IgA nephropathy

Question 6

What is secondary nephrotic syndrome?

Answer 6

Secondary causes of nephrotic syndrome include:

• Collage vascular diseases (eg, Systemic lupus erythematosis [SLE])
• Infectious etiology such as a recent group A strep infection (post-streptococcal glomerulonephritis), hepatitis B, and HIV
• Henoch-Schonlein purpura

Question 7

What is the epidemiology of nephrotic syndrome?

Answer 7

• Minimal-change disease is most common cause of nephrotic syndrome in children (90 percent of cases under the age of 10 years)
• Can occur at any age but is most common between the ages of 18 months and 5 years
• Affects boys more often than girls

Question 8

What are the signs of nephrotic syndrome?

Answer 8

• High levels of protein in the urine (proteinuria)
• Low levels of protein in the blood
• Swelling resulting from buildup of salt and water
• Less frequent urination
• Weight gain from excess water

Question 9

What is the histology associated with nephrotic syndrome?

Answer 9

• Appearance of the glomeruli is normal or with a minimal increase in mesangial cells and matrix
• Characteristic finding on electron microscopy is fusion and diffuse effacement of the epithelial cell foot processes.
• As implied in the name, the nephron appears relatively normal on light microscopy.

Question 10

What is the pathophysiology of hypoalbuminemia in nephrotic syndrome?

Answer 10

Major loss of albumin in the urine due to leaking through the defective capillary basement membrane and problems with renal tubular reabsorption/metabolism and decreased synthesis of the protein in the liver.

Question 11

What is the pathophysiology of hyperlipidemia in nephrotic syndrome?

Answer 11

In reaction to the decreased albumin, the liver is stimulated to make lipoproteins as well as albumin, which leads to hyperlipidemia and hypercholesterolemia. There is also decreased lipid clearance from circulation.

Question 12

What is the pathophysiology of generalized edema in nephrotic syndrome?

Answer 12

The fall in serum albumin concentration due to proteinuria results in a lowering of plasma colloid osmotic pressure. Fluid moves out of the vascular compartment into the interstitial space, and hypovolemia develops. Hypovolemia activates volume sensors and extra renal neurohumoral and hemodynamic mechanisms that signal the kidney to retain salt and water through increased renin-angiotensin-aldosterone, catecholamines, ADH and depressed natriuretic factor, leading to edema.

Question 13

What is the pathophysiology of hyponatremia in nephrotic syndrome?

Answer 13

Due to fluid overload caused by excessive sodium and water retention.

Question 14

What is the pathophysiology of pseudohyponatremia?

Answer 14

May also exist (dependent on lab process). Pseudohyponatremia will occur only if the lips are high enough to cause the blood to have a milky appearance.

Question 15

What is the prognosis for nephrotic syndrome?

Answer 15

• Although relapses are common, the long-term prognosis is excellent for children diagnosed with nephrotic syndrome due to minimal-change disease.
• They may have repeated relapses until the disease resolves spontaneously toward the end of the second decade of life, but there is no long-term renal damage.

Question 16

What is anasarca?

Answer 16

Severe generalized edema.

• Best seen in scrotal region of a male or labial region of a female
• Pitting edema

Question 17

What is a fluid wave?

Answer 17

Determines presence of ascites.

• With pt. lying supine, have an assistant place her hand and forearm firmly across the vertical midline of the abdomen (needed to prevent transmission of the fluid wave through adipose tissue)
• Place your hands on either side of the abdomen
• Tap on side of the abdomen firmly with your fingertips
• If ascites is present, you may feel a fluid wave hit your other hand.

Question 18

Enlarged tonsils in a child with nephrotic syndrome:

Answer 18

• Common in children 4-6 yrs of age because of peak growth of lymphoid tissue and frequent viral upper respiratory infections in children of this age.
• If no erythema or exudates, pharyngitis is unlikely.

Question 19

What are the most likely diagnoses for Periorbital swelling?

Answer 19

Allergy, URI, Sinusitis, Acute glomerulonephritis, Nephrotic syndrome, CHF, Hepatic failure

Question 20

What is a less likely diagnosis for periorbital swelling?

Answer 20

Periorbital cellulitis

Question 21

Periorbital swelling:

Answer 21

The most common causes are conjunctivitis, URI, and sinusitis. The swelling is usually painless and thought to result from the obstruction of venous drainage from periorbital structures into veins that pass through the sinuses because the veins are partially blocked by inflamed tissues in the sinuses.

Question 22

Allergy - cause of periorbital swelling:

Answer 22

• Abrupt onset and often accompanied by urticarial rash
• May also be swelling of other parts of the face, including the lips, tongue and other oropharyngeal structures
• If periorbital swelling is due to allergic conjunctivitis, will also find conjunctival injection
• May also find associated sneezing, itchy nose, and clear rhinorrhea, allergic shiners (dark circles under the eyes), Dennie’s lines (extra crease below the lower eyelid), and cobblestoning of the conjunctiva (fine bumps on the conjunctival mucosa)

Question 23

Upper respiratory infection (URI) cause of periorbital swelling:

Answer 23

• Acute duration
• May occur without redness as a result of inflammatory edema
• Associated cough or runny nose

Question 24

Sinusitis cause of periorbital swelling:

Answer 24

• Painless periorbital swelling and redness from ethmoid, frontal or maxillary sinusitis
• Duration can be more prolonged
• Associated nasal congestion, HA, cough, fever

Question 25

Acute glomerulonephritis cause of periorbital swelling:

Answer 25

- Most common presenting sign: Gross hematuria (tea-colored urine) - Periorbital swelling (due to hypoalbuminemia) - Abdominal distention - Frequently follows a URI - Usually presents with intravascular fluid overload leading to HTN

Question 26

Nephrotic syndrome cause of periorbital swelling:

Answer 26

- Periorbital swelling (often first sign of hypoalbuminemia) that improves when pt. is upright - Edema becomes more generalized and leads to pitting edema and ascites - Edema due more to interstitial fluid accumulation (as opposed to intravascular fluid overload), hence blood pressure usually normal (in severe cases, may become hypotensive) - Increasing tiredness and decreased appetite due to interstitial fluid accumulation

Question 27

Congestive heart failure (CHF) cause of periorbital swelling:

Answer 27

- Although common in adults with heart failure, edema is not often seen in children with heart failure - Shortness of breath is common and may be difficult to distinguish from fatigue. - Hepatomegaly common in CHF and may present as abdominal distention. - An S3 gallop would indicate an overloaded left ventricle, suggestive of CHF.

Question 28

Hepatic failure cause of periorbital swelling:

Answer 28

- Can cause generalized edema due to decreased production of albumin - Fatigue, abdominal distention, and jaundice would also be expected - Rare in an otherwise healthy child

Question 29

What is periorbital cellulitis?

Answer 29

- Usually unilateral - Hx of a local insect bite, trauma or infection - May also extend from another site of infection, such as sinusitis - Most often caused by pneumococcal Moraxella catarrhalis or by non-typable Homophilus influenza (incidence of Homophiles influenza type B has dropped markedly since the introduction of the Hib vaccine).

Question 30

What is on the differential diagnosis for ankle edema?

Answer 30

Arthritis involving the ankles, systemic allergic reaction, serum sickness, henoch-schonlein purpura.

Question 31

Arthritis involving the ankles:

Answer 31

Swelling localized to the ankle joint and other signs of ankle inflammation, such as limitation of range of motion and redness.

Question 32

Systemic allergic reaction:

Answer 32

Associated with urticarial rash

Question 33

Serum sickness:

Answer 33

Serum sickness can cause arthritis or periarticular swelling, but is also associated with an urticarial rash.

Question 34

Henoch-Schonlein Purpura:

Answer 34

A form of vasculitis that classically has a palpable purpuric rash of the lower extremities and abdominal pain associated with arthritis. Occasionally, joint swelling or abdominal pain can precede the rash.

Question 35

What is proteinuria?

Answer 35

Any disease causing inflammation of the renal parenchyma or nephritis can cause proteinuria.

Question 36

What is on the differential for proteinuria?

Answer 36

Nephrotic syndrome, Pyelonephritis, Acute glomerulonephritis

Question 37

What does NOT cause significant proteinuria?

Answer 37

Interstitial nephritis, Vesicoureteral reflux

Question 38

Pyelonephritis - proteinuria cause:

Answer 38

WBC and white blood cell casts would be seen with a urinary tract infection, causing a positive leukocyte esterase test on the dipstick.

Question 39

Acute glomerulonephritis - cause of proteinuria:

Answer 39

To a lesser degree than in nephrotic syndrome. Would also see red blood cells and red blood cell casts (positive heme test on the dipstick)

Question 40

Interstitial nephritis:

Answer 40

- Can be associated with red and white blood cells in the urine, but not a massive degree of proteinuria - Rare in children and usually caused by medication- such as methicillin (no longer avail. in US), NSAIDs, penicillins, cephalosporins, rifampin, sulfonamides - or infection

Question 41

Vesicoureteral reflux:

Answer 41

Does not cause significant proteinuria unless the patient also has significant renal parenchymal scarring

Question 42

What studies help to determine whether hypoalbuminemia is a result of loss of albumin in the urine, or lack of production in the liver?

Answer 42

Electrolytes, BUN, creatinine, AST, ALT, cholesterol, albumin, triglycerides and urinalysis.

Question 43

Urinalysis in children:

Answer 43

Children normally may excrete 1+ to 2+ (30-100 mg/dL) of protein during a fever or after significant exertion, which clears after resolution of the fever or exertion.

Question 44

What is orthostatic proteinuria?

Answer 44

A frequent finding in adolescents and does not signify renal disease. (There may be as much as 1500 mg/1.73 m2/24 hours, but protein excretion occurs when the patient is standing, not while recumbent. And when the first morning urine is checked it should be negative for protein.)

Question 45

What are the two mainstays of treatment for nephrotic syndrome?

Answer 45

1. Albumin infusion followed by IV furosemide | 2. Corticosteroids

Question 46

Albumin infusion followed by IV furosemide for nephrotic syndrome:

Answer 46

- If needed to relieve discomfort of dyspnea and edema or to reduce scrotal edema that may compromise testicular perfusion - NEVER treat with furosemide alone because it could lower intravascular volume to dangerously low levels, precipitating shock and increasing risk for venous thrombosis. - Treatment with albumin alone could lead to pulmonary edema if the blood volume expands too rapidly

Question 47

Corticosteroids for nephrotic syndrome:

Answer 47

- Most children between the ages of 1-10 years without gross hematuria and with a normal serum complement level should receive a trial of corticosteroids because the diagnosis is most likely minimal-change disease. Response to steroid divides patients into three groups: - Steroid responsive (greater than 95 percent of children) - Steroid resistant - Relapsing, or steroid-dependent

Question 48

What is the diet for a child with nephrotic syndrome?

Answer 48

- The average American child's diet already contains 1.5 grams more protein per day than is recommended, compensating for what is lost in the urine; adding more protein to the diet is not necessary. - Current guidelines recommend sodium restriction to a level of 1500-2000 mg daily - When in remission, child may have unrestricted diet

Question 49

What immunizations should a child with nephrotic syndrome have?

Answer 49

Give when in remission: - Polyvalent pneumococcal vaccine - Varicella vaccine - Annual influenza vaccine

Question 50

What are the main complications associated with nephrotic syndrome?

Answer 50

- Bacterial infections - Spontaneous peritonitis - Pneumonia - Cellulitis - Urinary tract infection - Venous thrombosis

Question 51

Bacterial infections:

Answer 51

A high index of suspicion, prompt evaluation (including cultures of blood and peritoneal fluid), and early treatment with broad-spectrum antibiotics to cover gram-positive and gram-negative organisms are critical in preventing life-threatening illness. Higher risk of infection is due to the following: - Decreased immunoglobulin levels - Edema fluid acting as a culture medium - Protein deficiency - Decreased leukocyte bactericidal activity - Immunosuppression from steroids - Decreased splenic perfusion due to hypovolemia - Urinary loss of a complement factor (properdin factor B) that opsonizes certain bacteria

Question 52

Spontaneous peritonitis:

Answer 52

- Frequent complication of nephrotic syndrome - Insidious presentation of fever and minimal other findings - Untreated, can lead to overwhelming sepsis and death, especially while patient is on steroids - Streptococcus pneumoniae is the most common pathogen causing peritonitis, but gram-negative bacteria can also be found.

Question 53

Venous thrombosis:

Answer 53

- Patients with nephrotic syndrome are predisposed to venous thrombosis involving any of the large veins of the body, including the sagittal sinus and pulmonary arteries. - Renal venous thrombosis is a relatively frequent complication in adults - Factors predisposing to venous thrombosis include: - Urinary loss of proteins that inhibit coagulation (antithrombin III) or increased fibrinolysis - Destabilization of platelets by hyperlipidemia - Increased fibrinogen levels - Increased blood viscosity due to rise in hematocrit (esp. if diuretics are used without albumin replacement) - Intense, prolonged therapeutic use of corticosteroids (thrombogenic)