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Flashcards in Pathology - Anderson L1/L2 Deck (84):

What are mendelian disorders?

mutations in single gene


What is an autosomal dominant disorder of the CT, manifested principally by changes in the skeleton, eyes, and CV sys?

marfan's syndrome


What defect causes Marfan's syndrome?

defective extracellular glycoprotein called *fibrillin-1, encoded by genes FBN1 or FBN2.


What are the clinical features of Marfan's syndrome? The life threatening features?

- Tall with long extremities and digits, joint laxity, chest deformities (pectus excavatum, pigeon-breast), *bilateral subluxation or dislocation of lens of eye (ectopia lentis), *high arched palate, *arachnodactyly
- Life-threatening feature: mitral valve prolapse; dilation of ascending aorta due to cystic medionecrosi (w/ hemorrhage via vasa vasorum), which may lead to *dissecting aneurysm--defects in tunica media of aorta


What are the forms of neurofibromatosis (basically what genes)?

- NF1 gene - most common; inc risk of malignant peripheral nerve sheath tumor; located on chromosome 17
- NF2 gene - bilateral acoustic neuromas; located on chromosome 22


Clinical features of neurofibromatosis?

multiple neurofibromas on skin, cafe-au-lait pigmentation, mental retardation, Lisch nodules (pigmented spots on iris)


3 examples of autosomal recessive diseases?

Tay-Sach's, cystic fibrosis, phenylketonuria


General details of Cystic Fibrosis (exclude the clinical features for now.)

- Disorder of ion transport of epithelial cells; affects fluid secretion in exocrine glands & epithelial linings
- Most common lethal genetic disease affecting Caucasian pop.
- Abnormal func of epith Cl- channel prot encoded by cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q31.2
- Abnormally viscous secretions—obstructs organ passages


Clinical feature of cystic fibrosis?

- Clinical features: chronic lung disease, pancreatic insufficiency, steatorrhea, malnutrition (malabsorption & vit A, D, E, & K deficiencies), hepatic cirrhosis, intestinal obstruction, & male infertility
- More features:
• Sweat gland ducts: Hypertonic sweat – dec reabsorption of NaCl
• Resp & intestinal epith: loss or reduction of Cl- secretion into lumen & inc active luminal Na absorption
• Inc H2O reabsorption lowering the H2O of surf fluid layer coating mucosal cells.
• Lungs – dehydration leads to defective mucociliary action & accum of hyperconcentrated, viscid secretions (recurrent pulm infections—pneumonia)
• Pancreas – bicarb transport = abnormal; dec luminal pH; inc mucin precip & plugging of ducts; inc binding of bact & pancreatic insufficiency


Tx for cystic fibrosis?

1. antimicrobial therapy
2. pancreatic enzyme replacement
3. bilateral lung transplant


What causes phenylketonuria? And what are the effects?

lack of phenylalanine hydroxylase (PAH) --> hyperphenylalaninemia & phenylketonuria


What are the clinical features of phenylketonuria?

- normal at birth; mental retardation shows by 6 mos
- seizures, neurological abnormalities, dec pigmentation of hair & skin, eczema, mousy/musty odor


What are examples of autosomal dominant disorders?

Marfan's syndrome, neurofibromatosis


Tx for phenylketonuria?

dietary restriction of phenylalanine


What are polygenic disorders caused by? Examples of polygenic disorders?

- Interactions betw variant forms of genes & environ factors
- diabetes mellitus, hypertension, schizophrenia, atherosclerosis


Examples of X-linked disorders?

hemophilia, Bruton's agammaglobulinemia, Duchenne's muscular dystrophy


What is a euploid?

exact multiple of haploid or 23


What is aneuploidy usu a result of?

error in meiosis or mitosis (nondisjnction); not exact multiple of 23


What is mosaicism?

2 or more pop of cells w/ diff chromosomal complements due to nondisjunction in early mitosis.
o Usu involves sex chromosomes & may lead to trisomy & monosomy


What is a ring chromosome?

Special form of deletion produced when break occurs at both ends of chromosome; damaged ends fuse into “ring.”


What is translocation?

- A segment of one chromosome is transferred to another.
- 2 types: balanced reciprocal; centric fusion (robertsonian)


Most common chromosomal disorder? And what is its most common cause?

Down Syndrome (Trisomy 21); *meiotic nondisjunction of chromosome 21


What are the clinical features of Down's Syndrome?

epicanthic folds, flat facial profiles, mental retardation, cardiac malformations, infections, inc risk of acute leukemia


Tell me the general details about Klinefelter Syndrome (excluding clinical features).

- Male hypogonadism (most common cause)—most pts are 47, XXY
- have *barr bodies in nucleus of epithelial cells from oral mucosa
- Inc risk of breast cancer, extragonadal germ cell tumors, & autoimmune diseases (i.e. lupus)


Clinical features of Klinefelter Syndrome?

- hypogonadism, inc in length betw soles & pubic bone, reduced facial, body, & pubic hair, gynecomastia (development of breast tissue), testicular atrophy, reduced testosterone
- Oral manifestations = taurodontism


Tell me the general details about Turner Syndrome (excluding clinical features).

- 45,X (57%); 43% are 45, X mosaics or 46,X,i(X(q10) – (isochromosome of long arm of X chromosome w/ deletion of small arm).
- Primary hypogonadism in females.


Clinical features of Turner Syndrome?

Short stature, *swelling of nape of the neck (webbing), low posterior hairline, increased carrying angle of arms (cubitus valgus), *shield-like chest w/ widely spaced nipples, cardiovascular malformations, lack of secondary sex characteristics, *streak ovaries (streaks of fibrous stroma devoid of follicles), *amenorrhea (absence of menstruation).


Tell me the general details about Fragile X Syndrome (excluding clinical features).

- *Triple repeat mutation (repeating sequence of 3 nucleotides, which disrupts its function; most common cause of familial mental retardation.)--usu C-G-G
- Discontinuity of staining or constriction in the long arm of the X chromosome.
- All males are affected.
- 50% of carrier females show mental retardation and 30% will have ovarian failure before age 40.
- Males = inc risk of progressive neurodegeneration in 60's.


Clinical features of Fragile X Syndrome?

Moderate to severe mental retardation, long face w/ large MD, large everted ears, & large testicles.


Details & clinical features of mutations in mitochondrial genes?

- Maternal inheritance only.
- Primarily affect organs that are dependent upon oxidative phosphorylation (skeletal muscle, heart, and brain.)
- Example: Leber hereditary optic neuropathy, leading to progressive blindness


What are genomic imprinting disorders? Examples of these disorders?

- Diseases arising from the inactivation of maternal (maternal imprinting) or paternal (paternal imprinting) genes during gametogenesis.
- ex: Prader-Willi syndrome, Angelman syndrome


What disease is associated with folic acid deficiency?



What are perinatal infections??

infections acquired transcervically or transplacentally


Prematurity complications can include...?

*hyaline membrane disease, intraventricular & germinal matrix hemorrhage


What are associated factors of Sudden Infant Death Syndrome (SIDS)?

prone sleeping position, sleeping on soft surfaces, & thermal stress


What are examples of benign pediatric neoplasms?

1. nevus flammeus
2. hemangioma
3. lymphangiomas
4. sacrococcygeal teratomas


benign pediatric neoplasm associated w/ capillary malformation of the skin?

nevus flammeus


benign pediatric neoplasm associated w/ rapid enlargement followed by gradual progression? (most common tumors of infancy)



benign pediatric neoplasm associated w/ lymphatic vessels?

lymphangiomas (cystic hygroma)


benign pediatric neoplasm associated w/ the most common teratoma and occurence in F>M?

sacrococcygeal teratomas


most primary tumor of kidney in children?

Wilm's tumor


where does a neroblastoma arise from?

from primordial neural crest event, with 40% arising from adrenal medulla.


What is the clinical course of coal workers' pneumoconiosis?

coal workers' pneumoconiosis; increasing pulmonary dysfunction, pulmonary hypertension, cor pulmonale.


most common chronic occupational disease in the world? and what is its cause?

silocosis; inhalation of crystalline silica (including quartz)


what is the primary effector of silicosis?

macrophage mediator TNF


What region does silicosis usually affect? If silicosis progresses, what are some consequences?

upper lobes of lungs; more susceptible to TB


What is the morphology of silicosis?

silicotic nodules (concentric hyalinized collagen fibers surrounding amorphous center)


What is the clinical course of silicosis?

pulmonary hypertension & cor pulmonale; inc risk of TB


Occupational exposure to asbestos is linked to?

Occupational exposure to asbestos is linked to:
• Parenchymal interstitial fibrosis
• Localized fibrous plaques or diffuse fibrosis of the pleura
• Pleural effusions (serous or bloody)
• Bronchogenic carcinoma
• Malignant pleural and peritoneal mesotheliomas
• Laryngeal carcinoma


Where region does asbestosis usually affect? What is the morphology of asbestosis?

• Effects lower lobes
• Pleural plaques of collagen w/ Ca2+
• Asbestos bodies = golden brown rods w/ translucent center


What is asbestosis and smoking associated with? What is it not associated with?

Associated smoking inc risk bronchogenic carcinoma, but NOT mesotheliomas


Families of asbestos workers are also at risk. T/F?



What are examples of chemical injuries?

ethanol, carbon monoxide


What are the effects of acute alcoholism?

affects mainly the CNS; may have reversible hepatic (fatty change or steatosis) & gastric changes (gastritis, ulceration)


What are the effects of chronic alcoholism?

cirrhosis of the liver, alcoholic hepatitis, inc risk of hepatocellular carcinoma
*alcoholic hepatitis hallmark = Mallory bodies
*is an inflammation process, not infection like HepB


Why do we get carbon monoxide poisoning?

- Hb's affinity to CO is 200x greater than for O2
- CarboxyHb = very stable


What occurs in acute CO poisoning?

- generalized cherry red skin & mucous membranes
- brain edema w/ punctuate hemorrhages & hypoxia induced neuronal changes


What occurs in chronic CO poisoning?

- hypoxoa & widespread ischemic changes in CNS, esp basal ganglia & lenticular nuclei
- possible recovery, but often w/ permanent neurological dmg


What are examples of metal pollutants?

lead, arsenic


What happens when you have lead poisoning?

- hard tissue deposits
- peripheral neuropathies (more common in adults) & CNS abnormalities (more common in kids)
- hypochromic microcytic anemia (small RBCs)
- stippling of RBCs
- "lead line" @ gingival margin
- renal problems


What is the "lead line" that forms at the gingival margin during lead poisoning?

- oral flora has hydrogen sulfide, and lead reacts w/ it & forms lead sulfide
- same w/ mercuric sulfide, which leads to destruction of alveolar bone (rapid bone loss & PD)


Where do you get arsenic poisoning and what happens during it?

- mines & smelting industry
- Acute: problems in GI, CV, & CNS
- Chronic: hyperpigmentation & hyperkeratosis (usu on palms & soles)
- premalignant for basal & squamous cell carcinomas


What are examples of industrial or environmental agents that cause diseases?

organic solvents, polycyclic hydrocarbons, dioxins, vinyl chloride


What are some examples of organic solvents? What are their acute and chronic effects? Benzene exposure causes what?

- benzene, chloroform, carbon tetrachloride
- Acute: dizziness, confusion
- Chronic: CNS depression, coma
*benzene exposure inc risk of leukemia


Where do we get polycyclic hydrocarbons & what does it cause?

- combustion of fossil fuels
- lung & bladder cancer


Where do you find Dioxins and what do they cause?

- in bleached coffee filters
- skin disorders, liver & CNS abnormalities


Where do we find vinyl chloride and what does it cause?

- in PVC pipe
- angiosarcoma of the liver


What are examples of physical injuries?

abrasions, contusions, lacerations, incisions, thermal burns


Clinical significance of thermal burns depends on what variables?

1. depth of burn
2. % of body surface involved
3. internal injuries
4. promptness & efficacy of therapy


What is a full thickness burn?

3rd/4th degree burn; white or charred, dry, anesthetic
- total destruction of epidermis & dermis


What is a partial thickness burn?

1st/2nd degree burn; pink, mottled w/ blisters & is painful


What are the effects of ionizing radiation?

- DNA dmg
- Fibrosis – replacement of dead parenchymal cells by connective tissue and the formation of scars and adhesions
- Organ Sys dmg


What are the most sensitive organs to ionizing radiation?

gonads, hematopoietic & lymphoid systems, lining of GI tract


What are the consequences of a vit A deficiency?

- deficiency in infancy = blindness
- other symptoms: dry skin, conjunctiva, ulceration of cornea


What are the consequences of a vit D deficiency?

- Deficiency in infants results in rickets - irritability, growth retardation, prominence of costochondral junctions ("rachitic rosary”), and bowing of the long bones
- Adults: osteomalcia (weak bone, diffuse skeletal pain, susceptible to fractures)


What are the consequences of a vit C deficiency?

scurvy (inadequate collagen syn. (weakened vasc. Walls), petechial hemorrhage, ecchymosis, subperiosteal hemorrhages

Oral probs: generalized gingival swelling w/ spontaneous hemorrhage (scorbutic gingivitis), ulcertation tooth mobility, periodontal bone loss


What are the consequences of a vit B1 (Thiamine) deficiency?

aka beriber; CV probs & neruollogical abnormalities (i.e. Wernicke’s encephalopathy)


What are the consequences of a vit B2 (Riboflavin) deficiency?

oral probs: glossitis, angular cheilitis, sore throat, and swelling and erythema of the oral mucosa, maybe normocytic, normochromic anemia, also candidiasis


What are the consequences of a vit B3 (Niacin) deficiency?

Deficiency is known as pellagra
- Triad: dermatitis, dementia, diarrhea
- Oral: Stomatitis, glossitis (red, smooth, raw tongue)


What are the consequences of a vit B6 (Pyridoxine) deficiency?

- weakness, dizziness, seizures
- oral: cheilitis, glossitis


What is penetrance?

relative tendency to clinically express genotype--high genotype = very likely to show phenotypically what is expressed genotypically


What is expressivity?

variations in clinical manifestations w/ positive genotype-- high expressivity = many diff things associated w/ gene mut.


What is a pleiotropy?

Many effects from mutation of one gene (ex. Marfan’s syndrome)


What is heterogeneity?

Many different genes causing one disease (retinitis pigmentosa)