| What is environmental pollution? | Air contains gases and particles that can cause changes in respiratory tree and lung parenchyma, effects may be delayed or immediate, acc to exposure, more often long latency time (Carcinogenic air containments like tobacco and asbestos) |
| How is air pollution effect? | Significant cause of M&M in risk pt (pulmonary/cardiac disease), causes include microorganisms and chemical and pollutants.
Air pollution (industrialized countries air (ozone, SO2, acid aeosols, particles <10micm), indoor tobacco smoke CO, NO2 and asbesots.
Ozone made of NO and volatile organic compounds (emissions of cars..), ozone toxicity mediated by production of free radicals injuring epithelia of respiratory tract and Type I alveolar cells and cause release of inflammatory mediators, causing URT inflammation and variable symptoms (asthma, emphysema)
Most harm done by particles <10micm inhaled and go to alveoli cause inflammation by macrophage and neutrophils rxn (e.g Anthracose) |
| How is metals environmental pollutants (lead)? | Lead (interferes w/Ca metabolism leads to hemato, skeletal, neuro, GI and renal toxicity, exposure by air, food, and water, ingested lead harmful for children absorb more than 50% of lead from food whereas adults only 15%.
In children BBB is more permeable and more suseptible to damage, so in children we see central effects and in adults we see peripheral demyelinating neuropathy. 80% bind in teeth and bone instead of Ca and remain for 20-30 years, 5-10% stay in blood and go to soft tissues.
Seen by lead lines radiodense, they inhibit healing of fractures, cause damage to proximal tubules, and cause microcytic hypochromic anemia (early sign of lead accumulation due to inhibition of heme synthesis in marrow erythroid progenitors) |
| What are effects of Tobacco? | It contains more than 2000 compounds, among them is nicotine (addiction), potent carcinogens (polycyclic aromatic HC, nitosamines, aromatic amines).
Risk of lung cancer related to pack years, contributes also to cancer of oral cavity, esophagus, pancreas, bladder.
There is direct irritant effect on mucosa (cause inflammation and mucus secretion (bronchitis)) and recruitment of leukocytes to the lung (incraesed elastase and lung injury emphysema).
Atherosclerosis and MI linked to cigarette (increase platelet aggregation and decreased O2 supply), maternal smoking leads to abortions, preterm birth, intrauterine growth retardation.
Passive smoke inhalation more risk of lung cancer 1.3 times than normal non smokers. |
| What are the effects of alcohol? | Most are metablized by ADH/ cytochrome p450/ catalase to acetaldehyde.
Acute alcoholism (effect CNS, hepatic and gastric injury possible, fat droplets may accumulate in cytoplasm of hepatocytes (steatosis))
Chronic alcoholism (massive bleed from gastritis, gastric ulcers, esophageal varices, cirrhosis associated)
Alcoholic hepatitis (steatosis, inflammation and ballooning degeneration hepatocellular injury. Cellular swelling of hepatocytes w/clumped IF called Mallory body. fibrosis not diagnostic, as disease progresses we see cirrhosis, mallory bodies persist several months after cessation of drinking and associated w/risk for cirrhosis)
CV effects (dilated congestive cardiomyopathy)
Fetus (fetal alcohol syndrome (microcephaly, retard)
Carcinogenesis (oral, esophageal, liver)
Pancreatitis (acute/chronic)
Malnutrition (ethanol consumed more than food lead to Vitamin B deficiencies) |
| What is pneumoconioses? | Deposits of inorganic dusts in lung tissues, exposure to airbourne containments, develop slowly ,principal ones are silicosis and asbestosis
Intensity linked to quantity of dust inhaled and duration of exposure and physical properties of dust inhaled and risk cofactors like smoking, we see signs of lung toxicity, fibrosis or tumor pathology, samples (BAL/biopsy) obtained show increased particles or fibers and classify condition as occupational disease |
| What is silicosis? | Fibrosing pneumoconiosis, in areas where particle deposits are most important and predominate at top of lungs centroacinary/ subpleural peribronchiolar territories forming nodules.
Observed by lymph node and pleura draining, we see anthracosis linked to accumulation of carbon particles and soot.
3 pathologies (alveolar lipoproteinosis (acute w/massive exposure), TB, cancer)
Silicotic nodules (very limited, maybe calcified, macrophages containing birefringents in polarized light (talc, mica and silicates) replaced by collagen gradually, old lesions are acellular, hyaline fibrosis w/swirling arrangment |
| What is asbestosis? | Pneumoconiosis cause diffuse interstitial fibrosing lung disease w/presence of fibers, asbestos is a family of fibrous silicates (most used is chrysotile), fibers of 200 microm are not stopped through upper airway reach distal lungs.
Numerous circumstances (cement 80% of asbestos use in france, electrical insulation, thermal , naval and automobile industries and filters, asbestos sale banned since 1997 in France)
Asbestosis is when asbestos is inhaled in bare mineral fibers which in lungs are covered by ferruginous sheath, found either in alveolar washing/ biopsy/ pulmonary excision.
Asbestos body is ferruginous sheath highlighted by iron staining (Perls stain) |
| What is injury produced by ionizing radiation? | Ionizing radiation removes tightly bound electrons causing collisions of free electrons w/other atoms.
Cause DNA damage and carcinogenesis (not precisely repaired damage, leads to mutations can manifest in years as cancer)
On organ systems DNA damage leads to rapid division of germ cells, in bone marrow and GI very sensitive to radiation injury, cause neoplastic transformation since not repaired and may cause vascular damage and sclerosis causing ischemic necrosis of parenchymal cells and replacement by fibrous tissues.
We see fibrosis (by radiotherapy in irradiated field, weeks or months after irradiation).
We get wide range of changes in chromosomes, mitotic spindle cause polyploidy/aneuploidy, we see apoptosis, abnormal nuclear cells for years giant cells/ pleomorphic nuclei.
In hemato may see marrow aplasia. |
| What are heriditary, familial and congenital anomalies? | Derived from parents transmitted through germ line (familial), congenital means at birth (may be genetic may be not like syphilis) and not all genetic are congenital (huntingtons needs 40 years...)
Congenital anomalies are most common cause of mortality in 1st year, 20% of fertilized ova are anomalous blightened from outset, others may be compatible w/early development only lead to spontaneous abortion, less severe anomalies allow prolonged intrauterine survival (stillbirth termination or permit life after birth but handicaps)
Congenital anomalies include malformations, disruptions, deformations, sequence, malformation syndrome. |
| What are congenital malformations? | Primary errors in morphogenesis, result of single gene or chromosomal defect, may be multifactorial, some involve single body systems (heart defects/ anencephaly) others multiple malformations |
| What are congenital disruptions? | Secondary destruction of an organ/body region previously normal, arise from extrinsic disturbance, not heritable so no recurrence w/other pregnancies.
Amniotic bands due to rupture of amnion form bands encircle, compress or attach parts of developing fetus, classic disruption |
| What are congenital deformation? | Common (2% of newborns), extrinsic disturbance, localized or generalized compression of fetus by abnormal biomechanical force, most common is uterine constraint 35-38 weeks of gestation (rapid increase in size of fetus outpacing uterine growth so we get decrease in amount of amniotic fluid, factors (maternal factors [first pregnancy, small uterus, malformed uterus...], fetal factors [oligohydramnios, multiple fetuses, abnormal fetal development, club feet]) |
| What are congenital sequences? | Cascade of anomalies triggered by one irritating aberration, one aberration leads to secondary effects in other organs.
Oligohydramnios (Potter) sequence (caused by chronic leakage of amniotic fluid cause of rupture, or uteroplacental insufficiency from maternal HTN/toxemia, or renal agenesis in fetus so no urine constitutes amnion. We get fetal compression flattened facies and positional abnormalities of hands and feet, dislocated hips, hypoplastic lungs, nodules in amnion. |
| What is malformation syndrome? | Constellation of congenital anomalies caused by single etiologic agent viral/chromosomal leads to affect several tissues
Aplasia (failure of organogenesis in primordium) hypoplasia (incomplete development/decreased size of organ) |
| What is agenesis? | Complete absence of organ and primordium, may be total lack of organ (renal agenesis), absence of an organ part (agenesis of corpus callosum) or lack of tissues within an organ (no germ cells in testicles - Sertoli Cell Only syndrome)
Bilateral renal agenesis is incompatible with life (stillborn) while unilateral uncommon but compatible w/life if no other anomaly is present. |
| What is atresia? | Absence of an opening, usually of a hollow visceral organ, such as the trachea and intestine.
May be blind esophagus (closed) or fistula (esophagus goes to trachea) usually blind upper esophagus w/fistula between lower esophagus and trachea is most common. |
| What is dysplasia? | Abnormal organization of cells resulting in abnormal histogenesis, Pathogenesis (renal dysplasia by abnormal metanephric differentiation reflect multiple genetic and somatic causes, we see undifferentiated tubules and ducts lined by cuboidal/ columnar epithelium, surrounded by mantels of mesenchyma, some muscles and collagen, we see rudimentary glomeruli and ducts cytically dilated, may be unilateral or bilateral, and kidney may have multiple cysts) |
| What are causes of congenital anomalies? | Genetic/ Environmental/Multifactorial, unknown cause in half- 3 forth of cases |
| What are anomalies related to remnants? | Embryonic ducts, branchial pounch, persistent foci of embryonal cells (nephrogenic/neuroblastic rests) |
| What is meckel diverticulum? | It is a blind outpouching of alimentary tract communicates w/lumen, most common is Meckel diverticulum, in ileum.
Less common in small intestine and ascending colon.
Characteristics (rule of 2): 2% of population, 2 feet of ileocecal valve, 2 inches long, twice more common in males, often symptomatic age 2 (4% only symptomatic).
It occurs as a result of failed involution of vitelline duct connecting lumen of developing gut to yolk sac, it extends from antimesenteric side of the bowel. All diverticuli are acquired and may lack muscularis or have attenuated muscularis propria, mucosa resembles small intestine, but may present ectopic pancreas/gastric tissue, secrete acid cause peptic ulceration of small intestine mucosa present w/occult bleeding/abdo pain. |
| What is thyroglossal duct cyst? | Most common developmental anomaly of thyroid gland, most common congenital neck mass, may be evident after adulthood.
Due to persistent cystic dilation of thyroglossal duct, embryonic tract characterized by presence of epithelial lined remnants and heterotopic thyroid tissue, cyst lined by respiratory epithelium/stratified squamous epi, thyroid follicles in cyst/duct wall. Mucus salivary-type glands can be found in cyst wall, secondary inflammation is common |
| What is Branchial pouch/ Cleft anomalies? | Incomplete obliteration of branchial apparatus, cyst, sinus, fistula, or cartilage in anterolateral neck, cysts derived from branchial cleft have squamous epithelium, cysts derived from pouch have respiratory epithelium, but repeated infections cause squamous metaplasia. |
| What are tumor-like lesions to be distinguished from true tumors? | Heterotopia is applied to microscopically normal cells or tissues that are present in abnormal locations. Ex: a rest of pancreatic tissue found in the wall of the stomach or small intestine, or a small mass of adrenal cells found in the kidney, lungs, ovaries, or elsewhere. These heterotopic rests are usually of little significance, but they can be confused clinically with neoplasms.
•Hamartoma refers to an excessive, focal overgrowth of cells and tissues native to the organ in which it occurs. Although the cellular elements are mature and identical to those found in the remainder of the organ, they do not reproduce the normal architecture of the surrounding tissue. The line of demarcation between a hamartomaand a benign neoplasm is often unclear |
| What are choristoma? | It is an ectopic island of normal tissue—heterotopic rest (normal tissue in an abnormal site) and is a congenital anomaly.
Presence of small nodular mass of normally organized pancreatic tissue in the submucosa of the stomach, duodenum, or small intestine. |
| What are hamartomas? | It is a disorganized growth of benign-appearing cells, composed of tissue of the region within it is found.
may be clonal/genetic translocation, heriditary syndromes associated (Tuberous sclerosis, cowden syndrome, PTEN hamatroma tumor, Peutz-Jegher syndrome...)
Seen in lung, breast, polyps in GI.
Pulmonary hamartoma (islands of disorgranized cartilage, bronchi and vessels but histologically normal) |
| What are tumors and tumor-like lesions in childhood? | Only 2% of all malignant tumors occur in infancy and
childhood; nonetheless, cancer (including leukemia) accounts for about 9% of deaths in the US in children (4 -14 years).
Benign more common than cancers, sometimes cause serious complications acc to size and location, difficult ot separate true tumors/neoplasms from tumor like lesions in infant/child.
Most common are hemangioma, lymphangioma, fibrous lesions and teratomas. Most common neoplasms are Soft-tissue tumors of mesenchymal derivation, contrasts with adults where most common is epithelial origin. |
| Give table of most common neoplasms in childhood. | . |
| What are teratomas? | May be benign well-differentaied cystic lesions (mature), indeterminate potential (immature) or malignant (other germ cell tumor)
two peaks (first at 2 years, second in late adolescence slow growing prenatal)
Most common in childhood is sacrococcygeal teratoma(40%) 4 times more common in girls, 10% of teratomas are congenital anomalies (hindgut/cloacal region anomaly)
75% mature, 12% malignant and lethal, remainder is immature have malignant potential neuroepithelial elements present, most are encountered at younger infants (<4months) malignants at much older, other sites are testis, ovaries, midline locations (mediastinum, retroperitoneum, head and neck) |
