Acute Bacterial Meningitis Beyond the Neonatal Period

Cause of bacterial meningitis and its treatment during the neonatal period (0-28 days)

are generally different from those in older infants and children

ETIOLOGY.

Organism -

First 2 mo of life - maternal flora or the environment of the infant - group B

Streptococcus, gram-negative enteric bacilli, and Listeria monocytogenes, H. influenzae

Bacterial meningitis in children 2 mo-12 yr of age is due to S. pneumoniae, N.

meningitidis, or H. influenzae type b.

Anatomic defects or immune deficits increase the risk of meningitis from less common

pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-

negative staphylococci, Salmonella spp, and L. monocytogenes.

EPIDEMIOLOGY.

- lack of immunity to specific pathogens

-- close contact (e.g., household, daycare centers, schools, military barracks) with

individuals having invasive disease,

-crowding, poverty,

-absence of breast-feeding for infants 2-5 mo of age.

The mode of transmission - person to person contact through respiratory tract secretions

or droplets. -

-host defense defects due to altered immunoglobulin production in response to

encapsulated pathogens may be responsible for the increased risk of bacterial meningitis

-defects of the complement system is associated with recurrent meningococcal infection,

-defects of the properdin system - risk of lethal meningococcal disease.

-Splenic dysfunction (sickle cell anemia) or asplenia (due to trauma, congenital defect,

staging of Hodgkin disease) -risk of pneumococcal, H. influenzae type b , meningococcal

sepsis and meningitis.

-T-lymphocyte defects (congenital or acquired by chemotherapy, AIDS, or malignancy) -

risk of L. monocytogenes infections of the CNS.

-Congenital or acquired CSF leak -cribriform plate and middle ear ,inner ear fistulas, CSF

leakage through a rupture of the meninges due to a basal skull fracture into the

cribriform plate or paranasal sinus- risk of pneumococcal meningitis.

-Lumbosacral dermal sinus and meningomyelocele - staphylococcal and gram-negative

enteric bacterial meningitis.

-Penetrating cranial trauma and CSF shunt

PATHOLOGY.

1. A meningeal exudate is distributed around the cerebral veins, venous sinuses,

convexity of the brain, and cerebellum and in the sulci, sylvian fissures, basal cisterns,

and spinal cord.

2. Ventriculitis

3. subdural effusions

4.. Perivascular inflammatory infiltrates

5. thrombosis of small cortical veins, occlusion of major venous sinuses, necrotizing

arteritis producing subarachnoid hemorrhage,

6. Cerebral infarction due to vascular occlusion from inflammation, vasospasm, and

thrombosis.

7. Inflammation of spinal nerves and roots produces meningeal signs,

8. inflammation of the cranial nerves produces cranial neuropathies of optic, oculomotor,

facial, and auditory nerves.

9. Increased intracranial pressure (ICP) - produces oculomotor nerve palsy due to the

presence of temporal lobe compression of the nerve during tentorial herniation. 10.

Abducens nerve palsy may be a nonlocalizing sign of raised ICP.

Increased ICP

  - cell death (cytotoxic cerebral edema),

   - cytokine-induced increased capillary vascular permeability (vasogenic

cerebral edema),

    - increased hydrostatic pressure

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) may produce

excessive water retention, increasing ICP.

Raised CSF protein levels = increased vascular permeability of the blood-brain barrier

and the loss of albumin-rich fluid from the capillaries

Hypoglycorrhachia (reduced CSF glucose levels) = due to decreased glucose transport

by the cerebral tissue.

Damage to the cerebral cortex -infarction, necrosis, lactic acidosis, hypoxia, bacterial

invasion (cerebritis), toxic encephalopathy (bacterial toxins), raised ICP, ventriculitis,

and transudation (subdural effusions).

These pathologic factors result in the clinical manifestations of impaired consciousness,

seizures, hydrocephalus, cranial nerve deficits, motor and sensory deficits, and later

psychomotor retardation.

PATHOGENESIS.

Mechanism of infection

(1) direct invasion from - suppurative focus in the middle ear or mastoid spreads

through the dura and extends to the pia-arachnoid, causing generalized meningitis;

(2) suppuration inside cranium - such as a subdural abscess, brain abscess, or lateral

sinus thrombophlebitis, which causes the meninges to become inflamed,

(3) hematogenous spread - from an infectious focus in the upper respiratory tract

hematogenous dissemination of microorganisms from a distant site of infection;

bacteremia usually precedes meningitis.

Bacterial colonization of the nasopharynx is the source of the bacteremia.

viral upper respiratory tract infection may enhance the pathogenicity of bacteria

Bacterial capsules interferes with opsonic phagocytosis

Splenic dysfunction also reduces opsonic phagocytosis

Bacteria gain entry to the CSF through the choroid plexus of the lateral ventricles and

the meninges and then circulate to the extra cerebral CSF and subarachnoid space.

Bacteria rapidly multiplies in the CSF

The inflammatory response - neutrophilic infiltration, increased vascular permeability,

alterations of the blood-brain barrier, and vascular thrombosis.

cytokine-induced inflammation continues after the CSF has been sterilized

It causes the chronic inflammatory sequelae of pyogenic meningitis.

CLINICAL MANIFESTATIONS.

Two patterns. 1. Sudden onset with rapidly progressive manifestations of shock,

purpura, disseminated intravascular coagulation (DIC) and death within 24 hr.

2. Meningitis is preceded by upper respiratory tract or gastrointestinal symptoms,

followed by nonspecific signs of CNS infection such as increasing lethargy and irritability.

General symptoms & signs

fever

anorexia

poor feeding,

symptoms of upper respiratory tract infection,

myalgias, arthralgias,

tachycardia,

hypotension,

cutaneous signs- petechiae, purpura, erythematous macular rash.

Meningeal irritation - nuchal rigidity, back pain, Kernig sign (flexion of the hip 90

degrees with subsequent pain with extension of the leg), and Brudzinski sign

(involuntary flexion of the knees and hips after passive flexion of the neck while supine).

younger than 12-18 mo, Kernig and Brudzinski signs may not be evident

Increased ICP -

headache,

emesis,

bulging fontanel or widening of the sutures,

oculomotor or abducens nerve paralysis,

hypertension with bradycardia,

apnea or hyperventilation,

decorticate or decerebrate posturing,

stupor, coma, or signs of herniation.

Papilledema suggest a more chronic process, such as the presence of an intracranial

abscess, subdural empyema, or occlusion of a dural venous sinus.

Focal neurologic signs usually are due to vascular occlusion.

Cranial neuropathies of the ocular, oculomotor, abducens, facial, and auditory nerves

Seizures - due to cerebritis, infarction, or electrolyte disturbances

Seizures that occur on presentation or within the first 4 days of onset are of no

prognostic significance.

Seizures that persist after the 4th day of illness and those that are difficult to treat are

associated with a poor prognosis.

Alterations of mental status - = irritability, lethargy, stupor, coma.

due to increased ICP, cerebritis, or hypotension

Comatose patients - poor prognosis.

DIAGNOSIS.

Do LP -get CSF -

-neutrophilic pleocytosis,

-elevated protein

-reduced glucose concentrations

-identify microorganisms on Gram stain and culture

-latex particle agglutination. - Antigen is most consistently detected in the CSF

- Blood culture

LP should be performed when bacterial meningitis is suspected.

Contraindications for an immediate LP include

(1) evidence of increased ICP (other than a bulging fontanel),

(2) severe cardiopulmonary compromise

(3) infection of the skin overlying the site of the LP.

Thrombocytopenia is a relative contraindication for immediate LP.

If an LP is delayed, immediate empirical therapy should be initiated.

CT scanning for evidence of a brain abscess or increased ICP also should not delay

therapy.

LP may be performed after increased ICP has been treated or a brain abscess has been

excluded.

LP is usually performed with a patient in the flexed lateral position

needle is passed into the L3-L4 or L4-L5 intervertebral space.

Turbid CSF is present when the CSF leukocyte count exceeds 200-400/cu mm. Normal

healthy neonates may have as many as 30 leukocytes/cu mm, and older children

without viral or bacterial meningitis may have 5 leukocytes/mm3 in the CSF; in both age

groups, there is a predominance of lymphocytes or monocytes.

-pleocytosis may be absent in patients with severe overwhelming sepsis and meningitis

and is a poor prognostic sign.

-Pleocytosis with lymphocyte predominance can occur in early stage of acute bacterial

meningitis;

- neutrophilic pleocytosis may be present in patients during the early stages of acute

viral meningitis.

Gram stain is positive in most (70-90%) patients with bacterial meningitis.

Traumatic LP makes diagnosis of meningitis difficult. Repeat LP at another interspace

may produce less hemorrhagic fluid, but this fluid usually also contains red blood cells.

In traumatic LP gram stain, culture, and glucose level can help in diagnosis

Do C&S of CSF in such cases

Differential Diagnosis.

Organisms causing Meningitis

S. pneumoniae

N. meningitidis

H. influenzae type b

Mycobacterium tuberculosis

Nocardia

Treponema pallidum (syphilis)

Borrelia burgdorferi (Lyme disease)

ungi, - Coccidioides, Histoplasma, and Blastomyces

infections in compromised hosts - Candida, Cryptococcus, and Aspergillus

parasites- Toxoplasma gondii , cysticercosis, resulting from infection with the larval

stages ( Cysticercus cellulosae) of the pork tapeworm Taenia solium;

viruses.

Meningeal irritation seen in - Focal infections of the CNS including brain abscess and

parameningeal abscess (subdural empyema, cranial and spinal epidural abscess) Upper

lobe consolidation

Non infectious cause of meningeal irritation -malignancy,

collagen vascular syndromes, and

exposure to toxins.

examination of the CSF with

specific stains (Kinyoun carbol fuchsin for mycobacteria, India ink for fungi), cytology,

antigen detection (bacteria, Cryptococcus),

serology (syphilis),

viral culture (enterovirus).

CT or MRI of the brain,

blood cultures,

serologic tests

brain biopsy.

TREATMENT.

Antibiotics started after LP is performed.

If there are signs of increased ICP or focal neurologic findings, antibiotics should be

given without performing an LP and before obtaining a CT scan.

Treatment of increased ICP.

treatment of associated multiple organ system failure, such as shock and adult

respiratory distress syndrome, is also indicated.

Initial Antibiotic Therapy.

Rationale -

Common organisms are S. pneumoniae, N. meningitidis, and H. influenzae type b.

Pneumococcus - sensitive to penicillin and cephalosporins

N. meningitidis - penicillin and cephalosporins,

Some H. influenzae type b produce b-lactamases and therefore are resistant to

ampicillin. These b-lactamase-producing strains are sensitive to the cephalosporins.

Third-generation cephalosporins = ceftriaxone (100 mg/kg/24 hr administered once per

day or 50 mg/kg/dose, given every 12 hr),

Duration of Antibiotic Therapy =10-14 days.

Intravenous penicillin (400,000 U/kg/24 hr) for 7 days is the treatment of choice for

uncomplicated N. meningitidis meningitis.

Uncomplicated H. influenzae type b meningitis - for 10 days. ampicillin (200 mg/kg/24

hr, given every 6 hr) should be given with ceftriaxone or cefotaxime if H influenza is

isolated

Partially treated meningitis with clinical suspicion but not with CSF evidence -

ceftriaxone or cefotaxime for 10 days.

If child does not respond to treatment, a parameningeal focus may be present and a CT

or MRI scan should be performed.

repeat LP is not indicated in patients with uncomplicated meningitis

Gram-negative bacillary meningitis should be treated for 3 wk or for at least 2 wk after

CSF sterilization

Side effects of antibiotic therapy of meningitis -

phlebitis,

drug fever,

rash, emesis,

oral candidiasis,

diarrhea.

Ceftriaxone may cause reversible gallbladder pseudolithiasis, detectable by abdominal

ultrasonography. This may produce emesis and right upper quadrant pain.

Corticosteroids.

Rapid killing of bacteria releases toxic cell products after cell lysis (cell wall endotoxin)

that precipitates the cytokine-mediated inflammatory response. The resultant edema

formation and neutrophilic infiltration may produce additional neurologic injury

intravenous dexamethasone, 0.15 mg/kg/dose given every 6 hr for 2 days, in the

treatment of children older than 6 wk with acute bacterial meningitis, especially for H.

influenzae type b.

Corticosteroid administration -

decreases fever

lowers CSF protein and lactate levels

reduction in permanent auditory nerve damage

Corticosteroids have maximum benefit if given just before antibiotics and should be

administered with 1-2 hr of antibiotics.

Complications steroid - include gastrointestinal bleeding, hypertension, hyperglycemia,

leukocytosis, and rebound fever after the last dose.

dexamethasone for longer than 2 days offers no benefit, may cause gastrointestinal

bleeding.

Supportive Care.

identify early signs of cardiovascular, CNS, and metabolic complications.

Pulse rate, blood pressure, and respiratory rate should be monitored

Neurologic assessment, including pupillary reflexes, level of consciousness, motor

strength, cranial nerve signs, and evaluation for seizures,

Important laboratory studies include -

blood urea nitrogen;

serum sodium, chloride, potassium, and bicarbonate

urine output and specific gravity

complete blood and platelet counts

coagulation factors (fibrinogen, prothrombin, and partial thromboplastin times) in the

presence of petechiae, purpura, or abnormal bleeding.

Patients should initially receive nothing by mouth = vomiting may cause aspiration.

intravenous fluid administration should be restricted to one half to two thirds of

maintenance  - 1,000 mL/ sq mt /24 hr

Fluid administration may be returned to normal (1,500 mL/ sq mt /24 hr) when serum

sodium levels are normal. (10 kg = 0.3 sq mt, 20 kg = 0.6 sq mt, 30 kg = 1.0 sq mt)

Fluid restriction is not appropriate in the presence of systemic hypotension.

shock must be treated to prevent brain and other organ dysfunction (acute tubular

necrosis, adult respiratory distress syndrome)

septic shock require fluid resuscitation and therapy with vasoactive agents such as

dopamine, epinephrine, and sodium nitroprusside

Treatment of neurological complications - increased ICP with subsequent herniation,

seizures, and an enlarging head circumference due to a subdural effusion or

hydrocephalus. Signs of increased ICP (other than a bulging fontanel or isolated coma)

should be treated with endotracheal intubation and hyperventilation (to maintain the P

CO2 at approximately 25 mm Hg).

To reduce ICP

1. intravenous furosemide (Lasix, 1 mg/kg) Furosemide may reduce brain swelling by

venodilation and diuresis

2. mannitol (20% solution - 7 ml/kg in 20 minutes) mannitol produces shifting of fluid

from the CNS to the plasma and excretion during an osmotic diuresis.

Seizures

intravenous diazepam (0.2 mg/kg/dose) slowly.

Serum glucose, calcium, and sodium levels - determine if hypoglycemia, hypocalcemia,

or hyponatremia is precipitating seizures.

Then give- phenytoin (15-20 mg/kg loading dose, 5 mg/kg/24 hr maintenance) to

reduce recurrence. Phenytoin is preferred to phenobarbital because it produces less CNS

depression

COMPLICATIONS

Neurological complications -

seizures

increased ICP

cranial nerve palsies

stroke

cerebral or cerebellar herniation

transverse myelitis

ataxia

thrombosis of dural venous sinuses

subdural effusions = Collections of fluid in the subdural space in infants. - result in a

bulging fontanel, diastasis of sutures, enlarging head circumference, emesis, seizures,

fever, and abnormal results of cranial transillumination. CT or MRI scanning confirms the

presence of a subdural effusion. symptomatic subdural effusion should be treated by

aspiration through the open fontanel. Fever alone is not an indication for aspiration.

SIADH - results in hyponatremia and reduced serum osmolality This may exacerbate

cerebral edema , produce hyponatremic seizures

Fever associated with bacterial meningitis usually resolves within 5-7 days of the onset

of therapy.

Prolonged fever is due to

intercurrent viral infection

nosocomial or secondary bacterial infection

thrombophlebitis

drug reaction

Pericarditis or arthritis

Thrombocytosis, eosinophilia, and anemia may develop during therapy for meningitis.

Anemia may be due to hemolysis or bone marrow suppression.

DIC seen in cases with shock and purpura

PROGNOSIS.

The highest mortality - - pneumococcal meningitis.

neurodevelopmental sequelae =mental retardation seizures

cognitive or intellectual impairment,

sensorineural hearing loss -labyrinthitis following cochlear infection- dexamethasone

reduces the incidence of severe hearing loss Æ audiologic assessment before or soon

after discharge from the hospital,

delay in acquisition of language

visual impairment

behavioral difficulties

The prognosis is poorest among infants younger than 6 mo

seizures occurring more than 4 days after starting treatment, coma or focal neurological

signs at the time of presentation have more long-term sequelae.

Repeated meningitis - three distinct patterns.

1. Recrudescence is reappearance of infection during therapy CSF culture reveals the

growth of bacteria that have developed antibiotic resistance.

2. Relapse occurs between 3 days and 3 wk after therapy and represents persistent

bacterial infection in the CNS (subdural empyema, ventriculitis, cerebral abscess) or

other site (mastoid, cranial osteomyelitis, orbital infection). Relapse is often associated

with an inadequate choice, dose, or duration of antibiotic therapy.

3. Recurrence is a new episode of meningitis due to reinfection with the same bacterial

species or another pyogenic pathogen.

Recurrent meningitis suggests the presence of an acquired or congenital anatomic

communication between the CSF and a mucocutaneous site or defects in immune host

defense

PREVENTION.

Vaccination and antibiotic prophylaxis

Source:DR.NS.MANI.MD Associate Professor in Pediatrics

Download This Lecture Note 

Asthma

A leading cause of chronic illness in childhood.

Asthma is the most frequent admitting diagnosis in children's hospitals

10-15% of boys and 7-10% of girls may have asthma at some time during childhood.

Asthma can lead to severe psychosocial disturbances in the family.

With proper treatment, however, satisfactory control of symptoms is usually possible.

It may be regarded as a diffuse, obstructive lung disease with

(1) Hyper reactivity of the airways to a variety of stimuli and

(2) reversibility of the obstructive process occurs either spontaneously or because

of treatment.

Other names -reactive airway disease, wheezy bronchitis, viral-associated wheezing, and

atopic-related asthma.

Bronchoconstriction and inflammation are the pathophysiologic factors. Mast cells,

eosinophils, activated T lymphocytes, macrophages, and neutrophils have key roles in the

inflammation of asthma.

Both large (>2 mm) and small (<2 mm) airways may be involved

Hyper reactivity of the airways, appears to be an intrinsic part of the disease and is

present in almost all asthmatic individuals.

This hyperresponsiveness manifests

As bronchoconstriction following exercise;

On natural exposures to strong odors or irritant fumes such as sulfur dioxide,

tobacco smoke, or cold air

On intentional exposures in the laboratory to inhalations of histamine or

parasympathomimetic agents

Airway hyperreactivity relates to the severity of the disease.

increased reactivity occurs

i.   during viral respiratory infections,

ii.   following exposure to air pollutants and allergens

iii.   to occupational chemicals in sensitized individuals,

iv.   following administration of b-receptor antagonists.

An acute decrease in airway irritability follows administration of b-receptor agonists,

theophylline, and anticholinergics, and decreased irritability follows chronic

administration of cromolyn, nedocromil, or systemic or inhaled corticosteroids.

A child with one affected parent has about a 25% risk of having asthma;

the risk increases to about 50% if both parents are asthmatic.

genetic predisposition combined with environmental factors may explain most cases of

childhood asthma.

EPIDEMIOLOGY.

onset at any age;

30% of patients are symptomatic by 1 yr of age,

80-90% of asthmatic children have their first symptoms before 4-5 yr of age.

Occasional attacks of slight to moderate severity,

Some experience severe, intractable asthma, -interferes with school attendance, play

activity, and day-to-day functioning.

most severely affected children have an onset of wheezing during the first yr of life and a

family history of asthma and other allergic diseases (particularly atopic dermatitis).

These children may have

1.   growth retardation unrelated to corticosteroid administration (although ultimate

height attainment usually is normal),

2.   chest deformity secondary to chronic hyperinflation,

3.   persistent abnormalities on pulmonary function testing.

The prognosis for young asthmatic children is good.

remission depends on growth in the cross-sectional diameter of the airways.

Risk factors for asthma

1.   poverty,

2.   maternal age less than 20 yr at the time of birth,

3.   birthweight less than 2,500 g,

4.   smoking by adult member

5.   small home size and over crowding

PATHOPHYSIOLOGY.

1.   bronchoconstriction,

2.   hypersecretion of mucus,

3.   mucosal edema,

4.   cellular infiltration,

5.   desquamation of epithelial and inflammatory cells.

inhaled allergens (dust mites, pollens, molds, cockroach, cat or dog allergens), vegetable

proteins, viral infection, cigarette smoke, air pollutants, odors, drugs (nonsteroidal anti-

inflammatory agents, b-receptor antagonists, metabisulfite), cold air, and exercise.

The pathology of severe asthma

1.   bronchoconstriction,

2.   bronchial smooth muscle hypertrophy,

3.   mucous gland hypertrophy,

4.   mucosal edema,

5.   infiltration of inflammatory cells (eosinophils, neutrophils, basophils,

macrophages),

6.   desquamation.

7.   Pathognomonic findings include Charcot-Leyden crystals (lysophospholipase

from eosinophil membranes), Curschmann spirals (bronchial mucous casts), and

Creola bodies (desquamated epithelial cells).

Mediators of inflammation  are released from local mucosal mast cells following

stimulation by allergens -.

Mediators such as histamine, leukotrienes C4 , D4 , and E4 , and platelet-activating factor

initiate bronchoconstriction, mucosal edema, and the immune responses (see Chapter

141).

The early immune response results in bronchoconstriction, is treatable with b2 -receptor

agonists, and may be prevented by mast cell-stabilizing agents (cromolyn or nedocromil).

The late-phase reaction occurs 6-8 hr later, produces a continued state of airway

hyperresponsiveness with eosinophilic and neutrophilic infiltration, can be treated and

prevented by steroids, and can be prevented by cromolyn or nedocromil.

Obstruction is most severe during expiration because the intrathoracic airways normally

become smaller during expiration.

airway obstruction is diffuse but not uniform throughout the lungs.

Segmental or subsegmental atelectasis may occur, aggravating mismatching of

ventilation and perfusion

Hyperinflation causes decreased compliance, with consequent increased work of

breathing.

Increased transpulmonary pressures, necessary for expiration through obstructed airways,

may cause further narrowing or complete premature closure of some airways during

expiration, thus increasing the risk of pneumothorax.

Increased intrathoracic pressure may interfere with venous return and reduce cardiac

output, which may be manifested as a pulsus paradoxus.

Mismatching of ventilation with perfusion, alveolar hypoventilation, and increased work

of breathing cause changes in blood gases

Hyperventilation of some regions of the lung compensates for the higher carbon dioxide

tension in blood that perfuses poorly ventilated regions.

it cannot compensate for hypoxemia while breathing room air because of the patient's

inability to increase the partial pressure of oxygen and oxyhemoglobulin saturation.

Further progression of airway obstruction causes more alveolar hypoventilation, and

hypercapnia

Hypoxia interferes with conversion of lactic acid to carbon dioxide and water, causing

metabolic acidosis.

Hypercapnia increases carbonic acid, which dissociates into hydrogen ions and

bicarbonate ions, causing respiratory acidosis.

Hypoxia and acidosis can cause pulmonary vasoconstriction,

cor pulmonale resulting from sustained pulmonary hypertension is not a common

complication of asthma.

Hypoxia and vasoconstriction may damage type II alveolar cells, diminishing production

of surfactant, which normally stabilizes alveoli. Thus, this process may aggravate the

tendency toward atelectasis.

ETIOLOGY.

Asthma involves - autonomic, immunologic, infectious, endocrine, and psychologic

factors

Neural bronchoconstrictor activity is mediated through the cholinergic portion of the

autonomic nervous system.

Vagal sensory endings - termed cough or irritant receptors, depending on their location,

initiate the afferent limb of a reflex arc, which at the efferent end stimulates bronchial

smooth muscle contraction.

Vasoactive intestinal peptide neurotransmission initiates bronchial smooth muscle

relaxation. Vasoactive intestinal peptide may be a dominant neuropeptide involved in

maintaining airway patency.

Humoral factors favoring bronchodilation include the endogenous catecholamines that

act on b-adrenergic receptors to produce relaxation in bronchial smooth muscle.

Locally produced adenosine, may contribute to bronchoconstriction.

Methylxanthines - deriphylline- are antagonists of adenosine.

Asthma may be due to abnormal beta-adrenergic receptor-adenylate cyclase function,

with decreased adrenergic responsiveness.

decreased numbers of beta-adrenergic receptors on leukocytes - may provide a structural

basis for hyporesponsiveness to b-agonists.

Immunologic Factors.

extrinsic or allergic asthma, exacerbations follow exposure to -dust, pollens, and danders.

such patients have increased concentrations of both total IgE

intrinsic --- no evidence of IgE involvement;

skin test results are negative

IgE concentrations low.

in the first 2 yr of life and in older adults (late-onset asthma

increased IgE levels may be due to atopy,

Viral agents - respiratory syncytial virus (RSV) and parainfluenza virus are most often

involved; in older children rhinoviruses. Influenza virus - with increasing age.

Viral agents -- stimulation of afferent vagal receptors of the cholinergic system in the

airways. An IgE response to RSV can occur in infants and children with RSV-associated

wheezing - Wheezing with RSV infection may unmask a predisposition to asthma.

Endocrine Factors.

Asthma may worsen in relation to pregnancy and menses, especially premenstrually,

may have its onset in women at menopause.

improves in some children at puberty.

Thyrotoxicosis increases the severity of asthma; the mechanism is unknown.

Psychologic Factors.

Emotional factors can trigger symptoms

effects of severe chronic illness such as asthma on children's views of themselves, their

parents' views of them, or their lives in general can be devastating.

Emotional or behavioral disturbances are related to poor control of asthma

CLINICAL MANIFESTATIONS.

acute or insidious.

Acute episodes - exposure to irritants such as cold air and noxious fumes (smoke, wet

paint) or exposure to allergens or simple chemicals,

Exacerbations precipitated by viral respiratory infections are slower in onset, with

gradual increases in severity of cough and wheezing over a few days.

Because airway patency decreases at night, many children have acute asthma at night.

The signs and symptoms

cough, which sounds tight and is nonproductive early in the course of an attack;

wheezing,

tachypnea,

dyspnea with prolonged expiration and use of accessory muscles of respiration;

cyanosis;

hyperinflation of the chest;

tachycardia and pulsus paradoxus,

Cough may be present without wheezing,

wheezing may be present without cough;

tachypnea also may be present without wheezing.

in extreme respiratory distress, wheezing—may be absent

child has difficulty walking , talking.

hunched-over, tripod-like sitting position that makes it easier to breathe.

Expiration is typically more difficult

children complain of inspiratory difficulty also

Abdominal pain is common, due to the use of abdominal muscles and the diaphragm.

The liver and spleen may be palpable because of hyperinflation of the lungs.

Vomiting is common - followed by slight relief of symptoms.

sweat profusely;

low-grade fever

fatigue may be severe.

barrel chest deformity is a sign of chronic, airway obstruction

Harrison sulci, = anterolateral depression of the thorax at the insertion of the diaphragm, -

in children with recurrent severe retractions.

Clubbing of the fingers is rare

Clubbing suggests other causes of chronic obstructive lung disease such as cystic fibrosis.

DIFFERENTIAL DIAGNOSIS.

1.   congenital malformations (of the respiratory, cardiovascular, or gastrointestinal

systems),

2.   foreign bodies in the airway or esophagus,

3.   infectious bronchiolitis,

4.   cystic fibrosis,

5.   immunologic deficiency diseases,

6.   hypersensitivity pneumonitis,

7.   allergic bronchopulmonary aspergillosis,

8.   a variety of rarer conditions that compromise the airway, including endobronchial

tuberculosis, fungal diseases, and bronchial adenoma ,

9.   alpha-1 antitrypsin deficiency

10. tropical eosinophilia and other parasitic infections

ASTHMA IN EARLY LIFE.

Wheezing in the infant -

anatomic and physiologic peculiarities

(1) a decreased amount of smooth muscle in the peripheral airways compared with adults

may result in less support;

(2) mucous gland hyperplasia in the major bronchi compared with adults favors increased

intraluminal mucus production;

(3) disproportionately narrow peripheral airways up to 5 yr of age result in decreased

conductance relative to adults and render the infant and young child vulnerable to disease

affecting the small airways;

(4) decreased static elastic recoil of the young lung prediposes to early airway closure

during tidal breathing and results in mismatching of ventilation and perfusion and

hypoxemia;

(5) highly compliant rib cage and mechanically disadvantageous angle of insertion of

diaphragm to rib cage (horizontal vs. oblique in the adult) increase diaphragmatic work of

breathing;

(6) decreased number of fatigue-resistant skeletal muscle fibers in the diaphragm leave

the diaphragm poorly equipped to maintain high work output;

(7) deficient collateral ventilation with the pores of Kohn and the Lambert canals

deficient in number and size.

development of atelectasis distal to obstructed airwaysis easier in child

The clinical, roentgenographic, and blood gas findings in asthma and bronchiolitis are

similar.

bronchiolitis caused by RSV peaks during the first 6 mo of life,

during the cold weather months,

second and third attacks are uncommon.

Previously well infants or young children develop -cough, tachypnea, and wheezing

require hospitalization.

recurrent episodes of coughing and wheezing with bacterial infections should be

investigated for cystic fibrosis or immunologic deficiency.

Chronic aspiration caused by swallowing dysfunction (usually in developmentally

delayed children) or gastroesophageal reflux also may cause recurrent cough and

wheezing in early life. Symptoms of respiratory distress often occur with or shortly after

feeding, and a chest roentgenogram is commonly abnormal.

obliterative bronchiolitis (usually a sequela of a severe viral insult, most often

adenovirus) and bronchopulmonary dysplasia

food allergy - during early life is controversial.

Positive skin test to foods are unusual in asthmatic infants, - usually milk, wheat, or egg

Eczema is associated with the subsequent appearance of asthma.

Eosinophilia greater than 400 cells/mm3 (and especially greater than 700 cells/mm3 ) and

high serum IgE concentrations predict continuing respiratory tract problems.

TREATMENT.

avoiding allergens,

improving bronchodilation,

reducing mediator-induced inflammation.

Systemic or topical inhaled medications are used,

minimizing exposure to irritants such as tobacco smoke, smoke from wood-burning

stoves, and fumes from kerosene , wet paint and disinfectants,

avoiding ice-cold drinks and rapid changes in temperature and humidity.

Pharmacologic therapy

Oxygen by mask or nasal prongs at 2-3 L/min

epinephrine = 0.01 mL/kg of the 1:1,000 (1.0 mg/mL)

repeat the same dose once or twice at intervals of 20 min

side effects of epinephrine (pallor, tremor, anxiety, palpitations, and headache)

Terbutaline, a more selective b2 -agonist, is available in an injectable form and is an

alternative to epinephrine.

The dose of 0.01 mL/kg of the 1:1,000 (1 mg/mL) - longer duration of activity, up to 4 hr.

The maximal dose of terbutaline by subcutaneous injection is 0.25 mL; this dose may be

repeated once, if necessary, after 20 min.

Inhalation of bronchodilator aerosols

less drug is given than would be required by the subcutaneous route;

side effects of injected drugs such as epinephrine are avoided.

aerosol therapy is more effective than epinephrine in reversing bronchoconstriction.

Salbutamol solution is safe and effective at a dose of 0.15 mg/kg (maximum 5 mg)

followed by 0.05-0.15 mg/kg at intervals of 20-30 min until response is adequate.

available as a 0.5% solution (5 mg/mL) to be diluted with 2-3 mL normal saline

Nebulization with oxygen at 6 L/min prevents hypoxemia

metered-dose inhaler, 3 to 10 puffs per dose, with a spacer

doses of 6 to 10 puffs

nebulized ipratropium bromide, 250-500 mg,

Both can be administered safely at intervals of 20 min for three doses and subsequently at

intervals of 2 to 4 hr if necessary.

Theophylline

aminophylline = 5 mg/kg for 5-15 min

intravenous dose should be held until the theophylline level is known.

Steroid therapy reduces the relapse and hospitalization rates.

Source:DR.NS.MANI.MD Associate Professor in Pediatrics

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Acute Poststreptococcal Glomerulonephritis

It is acute nephritic syndrome: the sudden onset of gross hematuria, edema, hypertension, and

renal insufficiency. Most common cause of gross hematuria in children next is IgA

nephropathy 

ETIOLOGY AND EPIDEMIOLOGY.

Acute poststreptococcal glomerulonephritis follows infection of the throat or skin with certain

"nephritogenic" strains of group A b-hemolytic streptococci.

In cold weather, poststreptococcal glomerulonephritis commonly follows streptococcal

pharyngitis,

In warm weather glomerulonephritis follows streptococcal skin infections.

PATHOLOGY.

Kidneys - symmetrically enlarged.

Light microscopy - all glomeruli appear enlarged

diffuse mesangial cell proliferation

Polymorphonuclear leukocytes are common in glomeruli

Crescents and interstitial inflammation may be seen in severe cases.

Immunofluorescence microscopy - deposits of immunoglobulin and complement on the

glomerular basement membranes (GBMs) and in the mesangium.

Electron microscopy - electron-dense deposits are observed on the epithelial side of the GBM

PATHOGENESIS.

depression in the serum complement (C3) level suggest that poststreptococcal

glomerulonephritis is mediated by immune complexes,

complement activation is primarily through the alternative (immune complex activated)

pathway.

CLINICAL MANIFESTATIONS.

rare before the age of 3 yr.

Onset 1-2 wk after an antecedent streptococcal infection.

asymptomatic microscopic hematuria with normal renal function

acute renal failure.

Depending on the severity of renal involvement,

edema,

hypertension,

oliguria.

Encephalopathy or heart failure due to hypertension or both

The edema is usually a result of salt and water retention, nephrotic syndrome may also occur.

Nonspecific symptoms such as malaise, lethargy, abdominal or flank pain, and fever are

common.

The acute phase generally resolves within 2 mo after onset, but urinary abnormalities may

persist for more than 1 yr.

DIAGNOSIS.

Urine - red blood cells (RBCs),

with RBC casts and proteinuria +, ++

Blood -

Polymorphonuclear leukocytosis

Normochromic anemia due to hemodilution and low-grade hemolysis.

The serum C3 level is usually reduced.

Renal function tests -Urea and creatinine

Throat culture may be positive

Elevated antibody titer to streptococcal antigen(s) - ASO titer may not rise after streptococcal

skin infections.

Best single antibody titer to measure is that to the deoxyribonuclease (DNase) B antigen. An

alternative is the Streptozyme test -a slide agglutination procedure - detects antibodies to

streptolysin O, DNase B, hyaluronidase, streptokinase, and nicotinamide-adenine

dinucleotidase.

Rrenal biopsy ordinarily is indicated. To exclude systemic lupus erythematosus and an acute

exacerbation of chronic glomerulonephritis.

DD -

Acute glomerulonephritis may also follow infection with coagulase-positive and -negative

staphylococci, Streptococcus pneumoniae, gram-negative bacteria, and certain fungal,

rickettsial, and viral diseases.

Bacterial endocarditis may also produce a hypocomplementemic glomerulonephritis with renal

failure.

COMPLICATIONS. - Are due to ARF

volume overload

heart failure

hypertension

Hyperkalemia

Hyperphosphatemia

hypocalcemia

acidosis

seizures

uremia

PREVENTION.

Systemic antibiotic therapy of streptococcal throat and skin infections does not eliminate the

risk of glomerulonephritis.

Family members of patients with acute glomerulonephritis should be cultured for group A b-

hemolytic streptococci and treated if culture positive.

TREATMENT.

Management is that of acute renal failure

10-day course of systemic antibiotic therapy, with penicillin therapy may be given but it does

not change the natural history of glomerulonephritis.

Bed rest if there is complication

Antihypertensive medications (diuretics, Angiotensin-converting enzyme inhibitors) are

indicated to treat hypertension and to avoid hypertensive complications.

PROGNOSIS.

Complete recovery occurs in more than 95% of children with acute post streptococcal glomerulonephritis.

Acute phase may be severe and lead to chronic renal insufficiency.

Appropriate management of the acute renal or cardiac failure and hypertension can avoid

mortality in the acute stage.

Recurrences are extremely rare. Hence no penicillin prophylaxis like Rheumatic fever

Source:DR.NS.MANI.MD Associate Professor in Pediatrics

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