General Data JN 2 yo/F Tatalon, Q.C. Date of admission: January 19,2009 Informant: Father...

Clerks GrandroundsGuanzon, Guerrero, Guerzon

Guevarra, Guinto, Gutierrez

General Data

• JN• 2 yo/F• Tatalon, Q.C.• Date of admission: January 19,2009• Informant: Father• Reliability: Good

PERIORBITAL and BIPEDAL EDEMA

Chief complaint:

History of Present Illness

10 days PTA

9 days PTA

• productive cough and colds with whitish sputum

• (-) fever• No consult done, no medications taken

• Swelling of both parotid areas• (+) fever (max T 38.6 C)• Consult at a health center

– Assessment: Parotitis (mumps) & Upper Respiratory Tract Infection

– Cefaclor 41 mg/kg/day– Paracetamol 17 mg/kg/dose


4 days PTA

3 days PTA

• (+) bilateral periorbital swelling• (+) tea-colored urine• (-) dysuria, frequency, urgency, fever,

abdominal pain

(+) progression of bilateral periorbital swelling

(+) increased abdominal girth

(+) bipedal edema

(-) oliguria


Few hours PTA

• Persistence of symptoms• Consult at the Philippine Children’s Medical

Center – Blood pressure 150/ 90– Urinalysis : hematuria and proteinuria ,– Dx: Acute glomerulonephritis– Advised admission but opted transfer to our

institution

Admission

Review of Systems

• No weight loss, change in appetite or activity• No rashes, pruritus, jaundice• No lacrimation, aural discharge, epistaxis, gum bleeding• No difficulty of breathing• No cyanosis, fainting spells• No vomiting, diarrhea, constipation, melena, hematochezia• No seizures, convulsions• No limitation of motion• No pallor, bleeding manifestations, easy bruisability

Feeding and Immunization History

• 24 Hour Food Recall– Breakfast: 1 cup rice, 1 piece chicken, 1 cup milk– Lunch: 1 cup rice, 1 piece chicken, 1 cup water– Afternoon snack: 1 piece bread– Dinner: 1 cup rice, 3 pieces of pork, 1 cup milk

• Milk: Lactum 1+3, 5 oz, 2x/day, 1:2 dilution• Actual Caloric Intake: 894 kilocalories• Recommended Energy Nutrient Intake: 1070 kilocalories• Immunization: Completed EPI, no booster doses

Developmental History

• At 2 years old:– Runs well; jumps– 3 word sentences– Feeds self with spoon– Removes clothes

at par with age

Past Medical History

• Acute gastroenteritis (9 months old) → confinement at a local hospital

• No previous surgeries• No previous blood transfusions• No asthma• No allergies

Family History

• (-) asthma, allergies• (-) renal diseases• (-) thyroid diseases• (-) hypertension• (-) DM• (-) cancer• (-) PTB• (-) seizures• (-) blood dyscracias

Family Profile

• Father: 32 y/o, college undergraduate, a mechanic, in good health

• Mother: 23 y/o, high school graduate, house wife, in good health

Socioeconomic and Environmental History

• Family rents an apartment type home that is well-lit and well-ventilated.

• Drinking water is obtained from a water refilling station and is not boiled.

• Waste is not segregated; garbage is collected regularly.

• No pets owned, but there are stray dogs in the area

• No factories nearby

Physical Examination

• General Survey: – Awake, alert, ambulatory, not in cardio-respiratory distress,

well hydrated, well-nourished

• Vital signs:– BP =140/90 (p95 105/63) – PR = 98 bpm, regular – RR = 24 cpm, regular – T = 37.1 °C– Wt = 14.5 (z score=0) Ht = 90.5 cm (z score=0)

Physical Examination

• Warm moist skin, no active dermatoses

• Pink palpebral conjunctivae, anicteric sclerae, (+) bilateral periorbital edema

• Midline nasal septum, (+) clear nasal discharge, turbinates not congested

• No tragal tenderness, non-hyperemic EAC, TM intact, AU

• Moist buccal mucosa, no ulcers, non-hyperemic posterior pharyngeal wall

• Supple neck, (+) palpable cervical lymphadenopathies

• Symmetrical chest expansion, (-) retractions, resonant on percussion, equal vocal and tactile fremiti, clear and equal breath sounds on both lung fields

• Adynamic precordium, AB at the 4th ICS L MCL, (-) murmurs

• AC = 52 cm, globular abdomen, NABS, (-) tenderness, liver span 4.3 cm R MCL, Traube space not obliterated,(-) fluid wave/shifting dullness, bladder not palpable

• Genitalia grossly female, with non-hyperemic labia majora and minora, (-) discharge, lesions, bleeding from introitus

• Pulses full and equal, no cyanosis, (+) grade 1 bipedal edema

Neurological Examination

• Alert, awake • Pupils 2-3 mm ERTL, smooth and equal EOM, (+) corneal reflex,

no facial asymmetry, tongue midline on protrusion, (+) gag reflex• No rest or intention tremors• MMT 5/5 on all extremities• DTR ++ on all extremities• No involuntary movement, no spasticity, no atrophy• No Babinski, no nuchal rigidity

Salient Features

(+) productive cough and colds

(+) tea-colored urine

Urinalysis : -hematuria -proteinuria

Blood pressure 140/90

(+) grade 1 bipedal edema

(+) bilateral peri-orbital edema

History Physical Examination

Approach to Diagnosis

• Look for a symptom, sign, or laboratory finding pointing to a group of diseases

Edema (periorbital and bipedal)

Hematuria and Proteinuria

Hypertension (BP 140/90)

RENALDISEASES

Nelson Textbook of Pediatrics 18th edition

Cola/brown urineProteinuria (>30mg/dL)

RBC castAcute Nephritic Syndrome

YES

Glomerular Hematuria

CBC, ElectrolytesBun, Crea, Serum Albumin, Cholesterol, ASO, C3.C4,

ANA, ANCA, 24 h urine total protein

NO

Extraglomerular Hematuria

Urine Culture→ Urine Ca/Crea, Sickle Prep, KUB US→UA of

parents and siblings, electrolytes, 24 h urine for Ca, crea, uric acid, oxalate, Cystogram/renal scan

Glomerular Causes of Hematuria in Children

• Isolated Renal Disease– IgA nephropathy– Membranoproliferative GN– Post-streptococscal GN– Thin glomerular BM

nephropathy– Alport syndrome– Membranous nephropathy– Focal segmental

glomerulosclerosis– Antiglomerular BM disease

• Multisystem Disease– SLE nephritis– Henoch-Schonlein purpura

nephritis– Hemolytic-uremic

syndrome – Wegener’s

Granulomatosis– PAN– Goodpasture syndrome– Sickle Cell glomerulopathy– HIV nephropathy


Differential Diagnosis

IgA NephropathyMembrano-

proliferative GN Idiopathic RPGN PSGN

Most common chronic glomerular disease

10-15 y/o, ♂>♀

Predominance of IgA mesangial deposits but lesser amounts of IgG, IgM, C3, and properdin are common

Majority present w/ gross hematuria, nephritic (50%), nephrotic (rare), or nephritic-nephrotic syndrome

Most common cause of chronic glomerulonephritis in older children and young adults (2nd decade of life)

MPGN 1mesangial proliferation, thickening , splitting of glomerular capillary walls; C3 and Ig deposits in the mesangial and subendothelial regions

MPGN 2capillary wall show irregular ribbon like thickening, cresecents are common

Characterized by the presence of crescents (proliferating epithelial cells of the capsule, fibrin, BM-like material, and macrophages)

Rapid progression to renal failure

Present nephrotic or nephritic (90%)

most common cause of acute glomerulonephritis in children

5-15 y/o, ♂>♀

Presents as nephritic syndrome (90%) or nephrotic

Acute renal failure in 50%



IgA NephropathyMembrano-

proliferative GN Idiopathic RPGN PSGN

Occurs in association with URTI and gastrointestinal infection, and may be associated with loin pain

Normal C3, ↑ serum IgA

MPGN 3reveal continuous subepithelial and subendothelial deposits with disruption of the lamina densa

Majority present as nephrotic syndrome, others as nephritic syndrome

Hypertension is common

Renal function: N or↓

↓C3, ↑ ASO

Normal C3, no immune deposits

Diffuse proliferation and IgG, C3, deposits, subepithelial humps

Follows a skin or throat infection

↑ ASO (70%), ↓C3, (+) Streptozyme test


Clinical Impression

• t/c Post-streptococcal Glomerulonephritis

Course in the Ward

On admission• the following lab tests were requested:

– Urinalysis– CBC with platelet– BUN, creatinine– Na, K– ASO– C3

• Low salt diet (limit Na to 0.7 g/day)• Limit fluid intake to 600 ml/day• Medications:

– Furosemide 7.5mg/SIVP q12 (0.51 mg/kg/dose) with strict BP precaution

1st HD:– Referred to Pedia-Nephro for co management– Amplodipine 5mg/tab ½ tab q24h– Furosemide was increased to 20mg/IV q12 h (1.4 mg/kg/dose)

2nd HD• IV furosemide was shifted to oral at 20mg/tab (1.4 mg/kg/dose)

3rd HD• Amlodipine and Furosemide were discontinued

Urinalysis

Color dark yellowTransparency turbidpH 7Sp. Gravity 1.005Albumin +++Sugar NegativeRBC over 100/hpfPus cell 10-15/hpfsquamous cell fewBacteria fewMucus threads few

CBC

Result Normal ValueHgb 100 90-140g/LRBC 3.78 3.7-5.3 x 10^12/LHct 0.3 0.28-0.42MCV 79 70-86 U^3MCH 26.4 29 ± 2 pgMCHC 33.4 34 ± 2 g/dlRDW 13.5 11.6-14.6MPV 6.8 7.4-10.4 flPlatelet 661 150-450 x 10 ^9/LWBC 15.5 6.0-17.5 x 10^9/L neutrophils 0.7 0.5-0.7 bands 0.01 0.00-0.05 segmenters 0.69 0.5-0.7 lymphocytes 0.29 0.2-0.4 eosinophils 0.01 0.00-0.05

Blood Chemistry

Result Normal valueNa 136 133-146mmol/LK 4.8 3.5-5.0 mmol/L

Result Normal valueBUN 6.7 5-18 mg/dlCreatinine 0.44 0.3-0.7 mg/dlC3 0.12 0.9-1.8ASO 948 0-200 IU/ml

Final Diagnosis

• Acute Poststreptococcal Glomerulonephritis

Acute Poststreptococcal Glomerulonephritis

• a classic example of the acute nephritic syndrome characterized by the sudden onset of gross hematuria, edema, hypertension, and renal insufficiency

• One of most common glomerular causes of gross hematuria in children surpassed only by IgA nephropathy

• follows infection of the throat or skin by certain “nephritogenic” strains of group A ß-hemolytic streptococci

• a male-to-female ratio of 2:1 has been reported

• most cases occur in patients aged 5-15 years


Pathogenesis

• the result of glomerular deposition or in situ formation of immune complexes

• streptococcal neuraminidase may alter host immunoglobulin G (IgG)

• IgG/anti-IgG immune complexes are formed and then collect in the glomeruli.

• AB to ASO, antihyaluronidase, DNAase-B, and streptokinase are also elevated

• the kidneys may be enlarged up to 50%

• Histopathologic changes include swelling of the glomerular tufts and infiltration with PMN

• Immunofluorescence reveals deposition of IGs and complement

Clinical Manifestations

• most common in children aged 5–12 yr and uncommon before the age of 3 yr

• develops 1–2 wk after an antecedent streptococcal pharyngitis or 3–6 wk after a streptococcal pyoderma.

• renal involvement varies from asymptomatic microscopic hematuria with normal renal function to acute renal failure.

• depending on the severity of renal involvement, edema, hypertension, and oliguria may occur. Specific symptoms such as malaise, lethargy, abdominal or flank pain, and fever are common.

• nephrotic syndrome may develop in 10–20% of cases


Clinical Manifestations

• Complications:– encephalopathy –toxic effects of Streptococcal bacteria on CNS– heart failure - hypertension or hypervolemia– hyperK, hyperPO4, hypoCa, acidosis, seizures, and uremia

• resolution of acute phase in 6–8 wk, urinary protein excretion and hypertension in 4–6 wk, persistent microscopic hematuria in 1–2 yr


Diagnosis

• Clinical Dx: acute nephritic syndrome + evidence of recent streptococcal infection + low C3 level

1) Urinalysis-RBCs, RBC casts, proteinuria, and PMNs

2) CBC-mild normochromic anemia may be present from hemodilution and low-grade hemolysis.

3) C3 level -reduced in the acute phase and returns to normal 6–8 wk

4) Evidence of a previous invasive streptococcal infectiona. positive throat culture -support the diagnosis or represent the carrier state.

b. ASO-elevated after a pharyngeal infection but rarely increases after streptococcal skin infections.

c. DNase B-single best test to document cutaneous infection

d. Streptozyme test-detects ASO, DNase B, hyaluronidase, streptokinase, and nicotinamide-adenine dinucleotidase using a slide agglutination test


Renal Biopsy

• considered only in the ff:– acute renal failure– nephrotic syndrome– absence of evidence for streptococcal infection or

normal complement levels. – when hematuria and proteinuria, diminished renal

function, and/or a low C3 level persist more than 2 mos from onset


Prognosis

• Complete recovery in more than 95% of children

• Mortality in the acute stage can be avoided by appropriate management of acute renal failure, cardiac failure, and hypertension.

• Infrequently, the acute phase may be severe and lead to glomerular hyalinization and chronic renal insufficiency


Goals of treatment

1) Treat the acute effects of renal insufficiency and hypertension– Na restriction– Diuresis– CCB, Vasodilators, ACEI

2) Limit Spread of Nephritogenic organism– 10 day course of Penicillin


JOURNALS

SUPPLEMENTARY JOURNALS

Incidence of APSGN

• The median APSGN incidence in children from less developed country studies was 24.3 per 100,000 per year

• Estimation of 470,000 cases of APSGN occur annually, 97% in less developed countries

The Current Evidence of the Burden of Group A Streptococcal Disease. World Health Organization. 2005

Mortality

“Mortality from APSGN is said to be less than 0.5%, less than 2.0% of patients progress to end stage renal disease, and most of

the deaths and cases of chronic disease occur in adults and/or after sporadic disease, whereas the majority of APSGN cases

occur in children and/or epidemics.”

The Current Evidence of the Burden of Group A Streptococcal Disease. World Health Organization. 2005

Risk of developing APSGN after streptococcal infection

“The risk of developing acute nephritis after streptococcal infection is 1%, and increases to 10–15% if the patient is infected with a

nephritogenic strain... This disorder usually affects children, and is more frequent in males. Immunity is lifelong, but recurrences may develop

after infection with a different nephritogenic strain.”

“Unlike rheumatic fever, AGN definitely occurs after

either pharyngeal or skin infection with GAS.”

L. Stickler. Poststreptococcal Glomerulonephritis. Elsevier Honorable Mention. 2003

Martin, et.al. Group A Streptococcus. Seminars in Pediatric Infectious Diseases. Elsevier. 2006

“Approximately 90% of cases of poststreptococcal glomerulonephritis are caused by only 3 of the 60 strains of group

A beta-hemolytic streptococci (GABHS)—types 12, 4, and 1. Sporadic poststreptococcal glomerulonephritis classically results from type 12 infections of the throat, and epidemic infection is the

consequence of infection with a variety of strains.”

“Glomerular function tends to improve rapidly. Edema usually resolves within 1 month of the onset of illness, and proteinuria,

within 2 months. Complement levels are decreased at the onset of disease and return to normal in 4 to 6 weeks. However, it may

take as long as 2 to 5 years before hematuria resolves.”


“Recovery rates in children are higher than those in adults. Children and adults with epidemic glomerulonephritis tend to have

favorable short- and long-term outcomes. Conversely, sporadic infections progress slowly to chronic glomerulonephritis in a small number of children, but up to one half of adults have progressive

deterioration. Sporadic infections tend to be more severe than epidemic cases because sporadic cases must be clinically

significant to be recognized.”


The use of Penicillin

“All patients diagnosed with APSGN should be treated with a full 10-day course of penicillin to eradicate the nephritogenic strain, regardless of throat culture results

or recognition of a site of GAS pyoderma. However, an important note is that treatment of impetigo or pharyngitis therapy generally is not thought to alter pre-existent poststreptococcal AGN or prevent the disease in patients who are in the

latent period. Although some data suggest that antibiotic therapy may have a small effect on prevention of PSGN, this finding has not been substantiated.”

“Family members also should be cultured for GAS. Family members with positive cultures should be treated appropriately, even in the absence of symptoms,to

prevent further transmission of a nephritogenic stain”

Martin, et.al. Group A Streptococcus. Seminars in Pediatric Infectious Diseases. Elsevier. 2006

The use of Penicillin

• Weighing the factors that go into drug selection for GABHS pharyngitis, current guidelines recommend penicillin (penicillin V or benzathine penicillin G) as the drug of choice for treatment of patients who are not penicillin allergic.

• All antibacterial agents approved for treatment of GABHS pharyngitis have near-equivalent efficacy, but that penicillin has a narrower spectrum of activity and is less costly than the other agents

• Erythromycin and cephalosporins as alternative drugs

Casey, et. al. The evidence base for cephalosporin superiority over penicillin in streptococcal pharyngitis. Elsevier. 2007

Possible causes of penicillin failure and cephalosporin superiority

1. Copathogenicity - bacteria susceptible to one class of drugs are protected by other colocalized bacteria or bacterial strains that lack the same susceptibility

• beta-lactamase–producing organisms are colocalized with GABHS in the pharynx of infected patients

• Beta-lactamase–producing organisms can protect GABHS from the antibacterial actions of penicillin

• Because certain cephalosporins are more stable in the presence of beta-lactamases than penicillins, the presence of beta-lactamase–producing organisms is more likely to inactivate penicillin than cephalosporin molecules and thereby interfere with the former group’s ability to eradicate GABHS from the pharynx.


Possible causes of penicillin failure and cephalosporin superiority

2. Co-aggregation of GABHS with beta-lactamase–producing M. catarrhalis enhances the attachment of GABHS to pharyngeal epithelial cells; the increase was 10-fold, and the result in colony counts was also 10-fold higher than when M. catarrhalis were not present.

3. Bacterial interference• Normal flora of the oropharynx, including a-hemolytic streptococci

that are important in protecting against colonization by GABHS, and oral penicillin potently suppresses a-streptococci (Sanders et al., 1976). In contrast, cephalosporins are less likely to eliminate pharyngeal a-hemolytic streptococci.


Theories of glomerularinjury in PSGN

• antigen is filtered and lodged in the capillary wall, where it reacts with host antibody

• a streptococcal product reacts with a glomerular antigen such that it is now seen as foreign, and an immune response ensues

• streptococcal antigen reacts with host antibody, forming a soluble complex that is filtered, but not cleared, by the glomerulus. These complexes are then deposited subendothelially along the basement membrane, where they react with complement. The complement cascade then stimulates phagocytosis and digestive activity at the basement membrane, leading to fragmentation and breakdown. This breakdown subsequently leads to the characteristic urinalysis findings.


Anti-C1q in APSGN

• prospectively investigate in more detail the role of anti-C1q in a large cohort of children with APSGN

• Levels of anti-C1q correlated negatively with serum concentrations of C1q and C3 suggesting an altered complement activation in the presence of the autoantibody.

• associated with more severe glomerulonephritis as judged by more pronounced proteinuria and elevated creatinine as well as more frequent oliguria, hypertension and lack of spontaneous resolution

Kozyro, et.al. Autoantibodies against complement C1q in acutepost-streptococcal glomerulonephritis. Journal of Clinical Immunology.2008

Sabiston Textbook of Surgery 18th edition. 2007.

Anti-C1q in APSGN

• Additional binding of anti-C1q to glomerular deposits of C1q alters the function and/or exacerbates the activation of the complement cascade which might be responsible for the negative correlation between levels of anti-C1q and C1q antigen

• The interference of anti-C1q with the complement cascade or even complement activation might lead to a critical aggravation of the glomerular pathology. However, the precise pathogenic mechanism of anti-C1q remains to be elucidated


Anti-C1q in APSGN

• The effect of anti-C1q on the activation of the classical pathway is rather mild but exacerbated on the level of C3 when control of the alternative pathway is insufficient

• Determination of anti-C1q might be an interesting parameter for clinicians allowing the early identification of patients at risk for more severe courses of the disease and/or lack of spontaneous resolution


Anti-C1q in APSGN

• In children with APSGN anti-C1q were found in about one third of the patients and associated with more severe disease manifestations as well as a lack of spontaneous recovery. These observations could be due to a potential pathogenic mechanism of anti-C1q in APSGN. Determination of anti-C1q in the diagnostic process of APSGN might help identifying patients at risk for a more severe course of disease.


IgG Fc fragments in APSGN


IgG Fc fragments in APSGN

• The administration of human or rabbit IgG Fc fragments to animals with initial steps of renal tissue injury may prevent the development of poststreptococcal glomerulonephritis. Judging from the experimental design, this inhibitory effect was due to blocking of IgG FcBPs of injected streptococci and thereby induction of circulating anti-IgG. Alternatively, Fc fragments bound circulating anti-IgG and, because of this, formation of immune complexes and their renal deposition were prevented.

Burova, et.al. Inhibition of experimental poststreptococcalglomerulonephritis in rabbits by IgG Fc fragments. International Congress series. 2006.

BACK UP

Acute glomerulonephritis

• sudden onset of hematuria, proteinuria, and red blood cell casts accompanied by hypertension, edema, and impaired renal function

Frequency

United States• Glomerulonephritis represents 10-15% of glomerular diseases.• Variable incidence has been reported due in part to the subclinical nature of the

disease in more than ½ of the affected population.• Despite sporadic outbreaks, incidence of poststreptococcal glomerulonephritis

has fallen over the last few decades. • Factors responsible for this decline may include better health care delivery and

improved socioeconomic conditions.• International• It remains much more common in regions such as Africa, the Caribbean, India,

Pakistan, Malaysia, Papua New Guinea, and South America. I• n Port Harcourt, Nigeria, the incidence of acute glomerulonephritis in children

aged 3-16 years was 15.5 cases per year, with a male-to-female ratio of 1.1:1; the current incidence has not changed much over the past 14 years.

• Immunoglobulin A (IgA) nephropathy glomerulonephritis (ie, Berger disease) is the most common cause of glomerulonephritis worldwide.

Mortality/Morbidity

• Most epidemic cases follow a course ending in complete patient recovery (as many as 100%).

• Sporadic cases of acute nephritis often progress to a chronic form. This progression occurs in as many as 30% of adult patients and 10% of pediatric patients.

• Glomerulonephritis is the most common cause of chronic renal failure (25%)?

• The mortality rate of acute glomerulonephritis in the most commonly affected age group, pediatric patients, has been reported at 0-7%.

History

• A thorough history should focus on the identification of an underlying systemic disease (if any) or recent infection.

• Nonspecific symptoms include weakness, fever, abdominal pain, and malaise.

• In the setting of a postinfectious acute nephritis, a latent period of up to 3 weeks occurs before onset of symptoms. However, the latent period may vary; typically 1-2 weeks for postpharyngitis cases and 2-4 weeks for cases of postdermal infection (ie, pyoderma).

• Onset of nephritis within 1-4 days of streptococcal infection suggests preexisting renal disease.

Symtoms

• Symptoms of acute glomerulonephritis include the following: – Hematuria is a universal finding, even if it is microscopic. Gross hematuria is reported

in 30% of pediatric patients. – Oliguria – Edema (peripheral or periorbital) is reported in approximately 85% of pediatric

patients; edema may be mild (involving only the face) to severe, bordering on a nephrotic appearance.

– Headache may occur secondary to hypertension; confusion secondary to malignant hypertension may be seen in as many as 5% of patients.

– Shortness of breath or dyspnea on exertion secondary to heart failure or pulmonary edema; usually uncommon, particularly in children.

– possible flank pain secondary to stretching of the renal capsule– Others: arthritis, pharyngitis,impetigo, respiratory infection, pulmonary hemorrhage,

heart murmur, scarlet fever,weight gain, abdominal pain, anorexia,back pain, skin pallor,palpable purpura, oral ulcers


– Triad of sinusitis, pulmonary infiltrates, and nephritis suggesting Wegener granulomatosis

– Nausea/vomiting, abdominal pain, and purpura observed with Henoch-Schönlein purpura

– Arthralgias associated with systemic lupus erythematosus (SLE)

– Hemoptysis occurring with Goodpasture syndrome or idiopathic progressive glomerulonephritis

– Skin rashes observed with a hypersensitivity vasculitis or systemic lupus erythematosus; also possibly due to the purpura that can occur in hypersensitivity vasculitis, cryoglobulinemia, and Henoch-Schönlein purpura

Postinfectious etiologies

• GAS:

(1) serotype 12 - due to an upper respiratory infection occurring primarily in the winter months

(2) attributed to serotype 49 - due to a skin infection usually observed in the summer and fall and more prevalent in southern regions of the United States

• Other specific agents include viruses and parasites, systemic and renal disease, visceral abscesses, endocarditis, infected grafts or shunts, and pneumonia.

• Other bacterial causes: diplococcal, streptococcal, staphylococcal, or mycobacterial. Salmonella typhosa, Brucella suis, Treponema pallidum, Corynebacterium bovis, and actinobacilli.

• Cytomegalovirus, coxsackievirus, Epstein-Barr virus, hepatitis B, rubella, rickettsial scrub typhus, and mumps are accepted as viral causes only if it can be documented that a recent group A beta-hemolytic streptococcal infection did not occur. Acute glomerulonephritis has been documented as a rare complication of hepatitis A.

• Fungal and parasitic: Attributing glomerulonephritis to a parasitic or fungal etiology requires the exclusion of a streptococcal infection. Identified organisms include Coccidioides immitis and the following parasites: Plasmodium malariae, Plasmodium falciparum, Schistosoma mansoni, Toxoplasma gondii, filariasis, trichinosis, and trypanosomes.

Systemic Causes

• Vasculitis (ie, Wegener granulomatosis causes glomerulonephritis that combines upper and lower granulomatous nephritides).

• Collagen vascular diseases (ie, systemic lupus erythematosus causes glomerulonephritis through renal deposition of immune complexes).

• Hypersensitivity vasculitis encompasses a heterogeneous group of disorders featuring small vessel and skin disease.

• Cryoglobulinemia causes abnormal quantities of cryoglobulin in plasma that result in repeated episodes of widespread purpura and cutaneous ulcerations upon crystallization

• Polyarteritis nodosa causes nephritis from a vasculitis involving the renal arteries. • Henoch-Schönlein purpura causes a generalized vasculitis resulting in

glomerulonephritis. • Goodpasture syndrome causes circulating antibodies to type IV collagen and often

results in a rapidly progressive oliguric renal failure (weeks to months). • Drug-induced (ie, gold, penicillamine)

Clinical Clues

• Timing in the urinary stream– start (distal urethra)– end (bladder neck, posterior, or

prostatic urethra)– throughout (upper urinary tract or

upper bladder)

• Physical characteristics of the urine– glomerular (cola-colored,

proteinuria >500 mg/day, dysmorphic RBCs, RBC casts)

– non-glomerular (pink /red, +/- clots, proteinuria <500 mg/d, other types of casts)

• Other symptoms– pain/fever/chills in UTI– CVA tenderness in pyelonephritis– Colicky pain radiating to the

groin/nausea/vomiting in nephrolithiasis

• Family Hx– Alport’s syndrome, polycystic

kidney disease, sickle cell syndromes, benign familial hematuria, and bleeding diathesis

Major Syndromes in Nephrology

• General data• Hx• Pe• Salient• Approach to diagnosis• Presenting manifestation• Clinical diagnosis (working dx)• Differential dx• Confirmation of working dx (course in the wards)• Work up• Management• Outcome

Discussion

HEMATURIARED URINE

Heme (+)• Hemoglobin• Myoglobin

DRUGS• Chloroquine• Ibuprofen• Metronidazole• Nitrofurantoin• Phenothiazin

es• Rifampin• Salicylates• Sulfasalazine

Dyes (beets, blackberries, food color)Metabolites• Homogentisic

acid• Melanin• Methemoglobin• Porphyrin• Tyrosinosis• Urates

MIMICS

Approach to Hematuria

Pelvocalyceal system, ureter, bladder, or urethra

-gross/terminal hematuria,blood clots

-non-dysmorphic RBCs • -minimal proteinuria

Upper Urinary Tract

LowerUrinary Tract

Glomerulus-brown/cola-colored/burgundy urineproteinuria >100 mg/dL - RBC cast and dysmorphic RBCs

Tubules -WBC & renal tubular epithelial cast

Glomerular Hematuria

RBC Cast Dysmorphic RBCs

Causes of Hematuria in Children

EXTRA GLOMERULAR

• The GFR may be estimated by measurement of the serum creatinine level. Creatinine is derived from muscle metabolism. Its production is relatively

• constant, and its excretion is primarily through glomerular filtration, although tubular secretion may become important in renal insufficiency.

• concentration of BUN, which is affected by state of hydration and nitrogen balance, the serum creatinine level is primarily influenced by the level of glomerular function.

• The serum creatinine is of value only in estimating the GFR in the steady state. For example, a patient may have a normal creatinine level without

• effective renal function very shortly after the onset of acute renal failure with anuria. In this clinical setting, serum creatinine may be an insensitive measure of

• decreased renal function, because its level does not rise above normal until the GFR falls by 30–40%.

• The precise measurement of the GFR is accomplished by quantitating the “clearance” of a substance that is freely filtered across the capillary wall and that is neither

• reabsorbed nor secreted by the tubules. The clearance (Cs ) of such a substance is

• 1733• Figure 500.2-5 Changes in the normal value of the glomerular

filtration rate, as measured by the creatinine clearance (CCR ), when standardized to mL/min/1.73?m2 of body surface

• area. The solid line depicts the mean value, and the shaded area includes two standard deviations. (Reprinted by permission of the publishers from McCrory W: Developmental Nephrology. Cambridge,

• MA, Harvard University Press. Copyright © 1972 by the President and Fellows of Harvard College.)

• that volume of plasma that, when completely “cleared” of the contained substance, would yield a quantity of that substance equal to that excreted in the urine over a

• specified time. The clearance is represented by the following formula:

• where Cs equals the clearance of substance s, Us reflects the urinary concentration of s, V represents the urinary flow rate, and Ps equals the plasma concentration of

• s. To correct the clearance for body surface area, the formula is• Figure 500.2-6 The serum creatinine in relation to age.

(Reprinted by permission of the publishers from McCrory W: Developmental Nephrology. Cambridge, MA, Harvard University

• Press. Copyright © 1972 by the President and Fellows of Harvard College.)

• The GFR is optimally measured by the clearance of inulin, a fructose polymer having a molecular weight of approximately 5,000. Because the inulin clearance

• technique is cumbersome, the GFR is commonly estimated by the clearance of endogenous creatinine. When the GFR is relatively normal, the creatinine clearance

• closely approximates the inulin clearance. As the GFR declines, an increasing proportion of the total creatinine in the urine is secreted by tubules, resulting in a

• creatinine clearance that progressively overestimates the actual GFR. Therefore, changes in renal function should be monitored by serum creatinine concentration

• when the serum creatinine level exceeds 2.0?mg/dL (180?μmol/L).

• The absence of plasma proteins larger than the size of albumin from the glomerular filtrate confirms the effectiveness of the glomerular capillary wall as a filtration

• barrier. Major factors restricting the filtration of these and other macromolecules include their size and their ionic charge.

• Clearance studies of macromolecules in animals have shown no restriction to the filtration of molecules up to the size of inulin. As size increases farther, filtration

• diminishes progressively, approaching zero for substances the size of albumin. Morphologic studies suggest that the size-selective filtration barrier resides within the

• GBM.• The endothelial cell, basement membrane, and epithelial cell of

the glomerular capillary wall possess strong negative ionic charges. These anionic charges are a

• consequence of two negatively charged moieties: proteoglycans (heparan sulfate) and glycoproteins containing sialic acid. Proteins in the blood have a relatively low

• isoelectric point and carry a net negative charge. Consequently, they are repelled by the negatively charged sites in the glomerular capillary wall, thus restricting

• filtration.

Distribution of tasks:

• Louise: – hx, pe and salient features– Read on mumps– Definition of oliguria. proteinuria,

normal progression of edema (head to feet or vice versa)

• Ai:– Ddx/clinical impression

• Kitse– Course in the Wards

• Mitch– PSGN to clinical manifestations

• Karla– Dx to goals of tx– Read on the different tests used to

document strep infection (rationale and technical aspects)

• Tin/Kitse– Journals (updates, prognosis, New

approach to treatment and diagnosis)

GO TEAM!!! LET’S ROCK THE GRANDROUNDS!!!

General Data JN 2 yo/F Tatalon, Q.C. Date of admission: January 19,2009 Informant: Father...

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Transcript of General Data JN 2 yo/F Tatalon, Q.C. Date of admission: January 19,2009 Informant: Father...