Friday, November 24, 2017

Pathophysiology of Cystic Fibrosis

Cystic fibrosis (CF
) is an inherited multisystem disorder of children and adults, characterized chiefly by obstruction and infection of airways and by maldigestion and its consequences.

CF is inherited as an autosomal recessive trait. The CF gene codes for a protein of 1,480 amino acids called the CF transmembrane regulator (CFTR).

Four long-standing observations are of fundamental pathophysiologic importance:
  1. failure to clear mucous secretions,
  2. a paucity of water in mucous secretions,
  3. an elevated salt content of sweat and other serous secretions, and
  4. chronic infection limited to the respiratory tract
In addition, there is a greater negative potential difference across the respiratory epithelia of CF patients than across the respiratory epithelia of control subjects. Aberrant electrical properties were also demonstrated for CF sweat gland duct epithelium. The membranes of CF epithelial cells are unable to secrete chloride ions in response to cyclic adenosine monophosphate (cAMP)–mediated signals and, at least in the respiratory tract, excessive amounts of sodium are absorbed through these membranes.

Cyclic AMP-stimulated chloride conductance is a function of CFTR itself; this function is absent in epithelial cells with many different mutations of the CFTR gene.

The postulated epithelial pathophysiology in airways involves an inability to secrete salt and secondarily to secrete water in the presence of excessive reabsorption of salt and water. The proposed outcome is insufficient water on the airway surface to hydrate secretions. Desiccated secretions become more viscous and elastic (rubbery) and are harder to clear by mucociliary and other mechanisms.These secretions are retained and obstruct airways, starting with those of the smallest caliber, the bronchioles. Airflow obstruction at the level of small airways is the earliest observable physiologic abnormality of the respiratory system.

Atrial Septal Defect


Atrial septal defects (ASDs) can occur in any portion of the atrial septum (secundum, primum, or sinus venosus), depending on which embryonic septal structure has failed to develop normally. Less commonly, the atrial septum may be nearly absent, with the creation of a functional single atrium. Isolated secundum ASDs account for ?7% of congenital heart defects.

The majority of cases of ASD are sporadic; autosomal dominant inheritance does occur as part of the Holt-Oram syndrome (hypoplastic or absent radii, 1st-degree heart block, ASD) or in families with secundum ASD and heart block.


An isolated valve-incompetent patent foramen ovale (PFO) is a common echocardiographic finding during infancy. It is usually of no hemodynamic significance and is not considered an ASD; a PFO may play an important role if other structural heart defects are present. If another cardiac anomaly is causing increased right atrial pressure (pulmonary stenosis or atresia, tricuspid valve abnormalities, right ventricular dysfunction), venous blood may shunt across the PFO into the left atrium with resultant cyanosis. Because of the anatomic structure of the PFO, left-to-right shunting is unusual outside the immediate newborn period. In the presence of a large volume load or a hypertensive left atrium (secondary to mitral stenosis), the foramen ovale may be sufficiently dilated to result in a significant atrial left-to-right shunt. A valve-competent but probe-patent foramen ovale may be present in 15–30% of adults. An isolated PFO does not require surgical treatment, although it may be a risk for paradoxical (right to left) systemic embolization.

Neonatal Cold Injury

Neonatal cold injury usually occurs in abandoned infants or those in inadequately heated homes during damp cold spells when the outside temperature is in the freezing range .

Clinical Features:
The initial features are apathy, refusal of food, oliguria, and coldness to touch. The body temperature is usually between 29.5 and 35°C (85–95°F), and immobility, edema, and redness of the extremities, especially the hands, feet, and face, are observed. Bradycardia and apnea may also occur. The facial erythema frequently gives a false impression of health and delays recognition that the infant is ill. Local hardening over areas of edema may lead to confusion with scleredema. Rhinitis is common, as are hypoglycemia and acidosis. Hemorrhagic manifestations are frequent; massive pulmonary hemorrhage is a common finding at autopsy.

Treatment :

Consists of warming and paying scrupulous attention to recognizing and correcting hypotension and metabolic imbalances, particularly hypoglycemia.

Monday, November 20, 2017

Enterobius Vermicularis Infection in Children

The cause of enterobiasis, or pinworm infection, is Enterobius vermicularis,which is a small (1 cm in length), white, threadlike nematode, or roundworm, that typically inhabits the cecum, appendix, and adjacent areas of the ileum and ascending colon. Gravid females migrate at night to the perianal and perineal regions, where they deposit up to 15,000 eggs.Eggs embryonate within 6 hr and remain viable for 20 days.

Human infection occurs by the fecal-oral route typically by ingestion of embryonated eggs that are carried on fingernails, clothing, bedding, or house dust. After ingestion, the larvae mature to form adult worms in 36–53 days.

Enterobius infection may cause symptoms by mechanical stimulation and irritation, allergic reactions, and migration of the worms to anatomic sites where they become pathogenic.

Pinworm infection is innocuous and rarely causes serious medical problems. The most common complaints include itching and restless sleep secondary to nocturnal perianal or perineal pruritus. The precise cause and incidence of pruritus are unknown. They may be related to the intensity of infection, psychologic profile of the infected individual and his or her family, or allergic reactions to the parasite.

Wednesday, November 15, 2017

Nail Separation

Onycholysis indicates separation of the nail plate from the distal nail bed.

Common causes are 
  • trauma, 
  • chronic exposure to moisture, 
  • hyperhidrosis, 
  • cosmetics, 
  • psoriasis, 
  • fungal infection (distal onycholysis), 
  • atopic or contact dermatitis, 
  • porphyria, 
  • drugs (bleomycin, vincristine, retinoid agents, indomethacin, chlorpromazine [Thorazine]), and 
  • drug-induced phototoxicity from tetracyclines or chloramphenicol.
Beau lines are transverse grooves in the nail plate that represent a temporary disruption of formation of the nail plate. The lines 1st appear a few weeks after the event that caused the disruption in nail growth. A single transverse ridge appears at the proximal nail fold in most 4–6 wk old infants and works its way distally as the nail grows; this line may reflect metabolic changes after delivery.

Clinical Manifestations of Congenital Hypopituitarism.

The child with hypopituitarism is usually of normal size and weight at birth although those with MPHD and genetic defects of the GH1 or GHR gene have birth lengths that average 1 SD below the mean. Children with severe defects in GH production or action are more than 4 SD below the mean by 1 yr of age. Those with less severe deficiencies grow at rates below the 25% for age and gradually diverge from normal height percentiles. Delayed closure of the epiphyses permits growth beyond the normal age when growth should be complete.

Infants with congenital defects of the pituitary or hypothalamus usually present with neonatal emergencies such as apnea, cyanosis, or severe hypoglycemia with or without seizures.

Microphallus in boys provides an additional diagnostic clue.

Deficiency of GH may be accompanied by hypoadrenalism and hypothyroidism.

Prolonged neonatal jaundice is common. It involves elevation of conjugated and unconjugated bilirubin and may be mistaken for neonatal hepatitis.

The head in the toddler is round, and the face is short and broad. The frontal bone is prominent, and the bridge of the nose is depressed and saddle-shaped. The nose is small, and the nasolabial folds are well developed. The eyes are somewhat bulging. The mandible and the chin are underdeveloped, and the teeth, which erupt late, are frequently crowded. The neck is short, and the larynx is small. The voice is high-pitched and remains high after puberty. The extremities are well proportioned, with small hands and feet. Weight for height is usually normal, but an excess of body fat and a deficiency of muscle mass contributes to a pudgy appearance.