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168 Cards in this Set

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Describe Histamine's location, function, and properties for release
Preformed substance found in: Mast cells, basophils, platelets
Vasodilation of arterioles
Increases permeability of venules
Released due to: Physical injury, IgE, C3a/C4a, IL-1, PLT aggregation,...
Describe Serotonin's location, function, and properties for release
Found in: Platelets and enterochromaffin cells
Vasodilation of arterioles
Increased permeability of venules
Released due to: Physical injury, IgE, C3a/C4a, IL-1, PLT aggretation,...
Describe Leukocyte adhesion deficiency Type I and Type II
Type I: Defect in biosynthese of B2 (No firm adhesion form VCAM-1 or ICAM-1)
Type II: Absence of sialylated oligosaccharides receptor for E and P selectins (No Rolling/Loose Adhesion)
Describe the genetic representation of Chronic Granulomatous Disease and what happens?
X-Linked (Defect in membrane NADPH - No oxidative "Burst")
Autosomal Recessive (defect in cytoplasmic NADPH oxidase
Common to get infections
Describe the genetic representation of myloperoxidase deficiency (MPO-Deficiency) and what happens
Absent MPO-H2O2 system (No oxidative "Burst")
Most common Neutrophil Defect
Common to acquire infections
Describe the genetic representation of Chediak-Higashi Syndrome and what happens
Autosomal recessive
Lysosomes cannot fuse w/ phagosomes
Lysosomes become large (No phagocytosis)
Neutropenia, albinism, nerve defects, bleeding, and Immunodeficiency
Common to acquire infections
Define Sinus tract and the following exudates: serous, fibrinous, Catarrhal, purulent/suppurative, hemmorhagic, and fibrinopurulent.
Sinus Tract: Passage or path formed by discharge of a deep abscess to the surface of skin or a mucosal membrane
Serous - serum like exudate
Fibrinous - fibrin rich exudate
Catarrhal - exudate from mucous membranes
purulent/supperative - leukocyte rich exudate
hemmorrhagic - bloody exudate
fibrinopurulent - inflammatory edema fluid containing puss and fibrin
What does DAF stand for, what does it do, and what happens if you are deficient in it?
Decay-Accelerating Factor
Located in cell membrane - dissociation/cleaving of C3b
Defect: causes Paroxysmal Nocturnal Hemoglobinuria (intravascular hemolysis/anemia at night while sleeping)
What is C1INH and what does it do and what happens if you are deficient?
C1 inhibitor
Plasma protein
Blocks C1 binding to immune complexes
Defect: causes stress, trauma of skin, larynx and intestines known as Hereditary angioneurotic edema
Name the chemotactic agents?
C5a, LTB4, IL-8, kallikrein and there are others, but I don't have them in front of me...
Exogenous: N-formyl-methionine (on bacteria)
What does bradykinin do?
Increases permeability
Vasodilation
Bronchiolar smooth muscle contraction
Pain
Inactivation of kininases/angiotensin converting enzyme
What does release of kallikrein do?
Autoamplification
Chemotaxis
C4a formation
What does Plasmin do?
Cleaves C3 and forms C3a
degrades fibrin to form fibrin split products (permeability; vasoactive mediators)
activates hageman factor (XII) for amplification
What are the inflammatory actions of the prostaglandins?
PGI2 (Endothelium) - Vasodilation
PGE2 - Vasodilation and pain
Thromboxane A2 (Platelets) - Vasoconstriction
What are the inflammatory actions of the Leukotrienes?
LTC4, D4, and E4 - vasoconstriction, increased permeability
LTB4 - powerful chemotaxis
What does PAF stand for and do?
Platelet activating factor
Platelet stimulation, vasoconstriction, and bronchoconstriction
What do IL-1 and TNF do?
Endothelial "activation": Increased leukocyte adhesion, synthesis of PGI2, Thrombogenicity, Secretion of other cytokines (IL-1, IL-8, PDGF)
Fibroblasts (Involved in repair and fibrosis): increased collagen synthesis, fibroblast proliferation
Acute phase response: fever, neutrophilia, sleep, decreased appetite, hypotension
What are the chemokines and what do they attract?
IL-8: Neutrophils
Monocyte Chemoattractant Protein: Monocytes
Macrophage INflammatory Protein: Macrophages
RANTES (Regulated and normal T-Cell expressed and Secreted): all cell types except neutrophils
What causes increased vascular permeability?
Histamine
Anaphylatoxins (C3a and C5a)
Kinins
Leukotrienes (C, D, E)
PAF
What causes Vasodilation?
PGI-2
PGE-2
Nitric Oxide
What are chemotactic?
C4a, LTB4, chemokines (IL-8), N-fmet
What is acute phase reaction and what causes it?
It is: fever, neutrophilia, sleep, decreased appetite, hypotension
caused by: IL-1 and TNF
What causes fever?
IL-1, TNF, and PGs
What are the anti-proteases that prevent tissue damage?
Alpha-1 antitrypsin
Alpha-2-macroglobulin
What causes chemokines cause pain?
PGs and Bradykinin, oh and Substance P
Where is neuropeptide substance P from and what does it do?
From Lung and GI
causes Pain and increased vascular permeability
what produces IFN-Gamma and what does it do?
Produced by lymphocytes and causes macrophage activation
What are the big 3 of chronic inflammation (the cells)?
Macrophages
Lymphocytes
Plasma Cells
What are the four R's of Immunity?
Recognize the Antigen
Recruite the appropriate cells/factors
Removal
Repair
Of the 4 R's of immunity what does it mean recognize the antigen?
Interleukin-1 alpha/beta and TNF alpha/beta
Induce expression of adherance molecules
Induce cytokine networks
induce physiological changes (Fever, increased pulse/blood pressure)
Of the 4 R's of immunity what does it mean Recruit the appropriate cells/factors?
Interleukin-8: Polymorphonuclear leukocyte chemotaxin and T-lymphocyte chemotaxin
Monocyte chemotactic protein -1 (from Activated T-Cells): Peripheral blood monocyte chemotaxin andperipheral blood monocyte activator
Of the 4 R's of immunity what does it mean Removal?
Interferon Gamma: Increases MHC expression, increases killing activity of phagocytes, increases Fc receptor (for antibodies) expression, activates macrophages
Interleukin-4: increases killing activity of phagocytes and stimulates B-cell maturation (Lymphocytes --> B-cells)
Interleukin-6: Stimulates acute phase response and stimulates antibody synthesis
Of the 4 R's of immunity what does it mean Repair?
TGF-beta: stimulate cell proliferation and increase collagen production
FGF - stimulates fibroblast growth and stimulates growth of new blood vessels
VEGF - promotes angiogenesis
What secretes IL-2 and what does it do?
T-cells can secrete IL-2 to activate more T-cells in a granulomatous inflammation response.
What are the Primary histologic features of granulomatous inflammation?
Angiogenesis and fibrosis
In granulomatous inflamation what causes angiogenesis?
FGF and VEGF promote angiogenesis and increase vascular permeability
In granulomatous inflammation what causes fibrosis?
Migration and proliferation of fibroblasts at site of injury triggered by TGF-beta, PDGF, EGF, FGF cytokines, IL1 and TNF alpha.
(Macrophages release the TGF-beta, PDGF, and FGF)
What is the timeline for healing of a myocardial infarct?
7-10 days: early formation of fibrovascular granulation tissue at margin
10-14 days: Well established granulation tissue with collagen deposition
2-8wks: increased collagen deposition with decreased cellularity
>2months: Dense collagenous scar
What happens in a cerebral infarct?
Liquifactive necrosis resulting in a cyst
No fibrosis/scarring
Some gliosis around margins
Where is PDGF stored, why is it released, and what releases it?
Stored in platelet alpha granules
Released upon activation ot cause migration and proliferation of fibroblasts, smooth muscle cells and monocytes
Can be made by: macrophages, endothelial cells, smooth muscle cells, and tumor cells
What are the functions of FGF?
Angiogenesis
Wound repair
development and hematopoiesis
What is the function of VEGF
AKA vascular permeability factor
Functions in vasculogenesis and angiogenesis
What makes TGF-Beta and what does it do?
Produced by Platelets, endothelial cells, and macrophages
It is chemotactic for monocytes
cuases angiogenesis
Has a wide range of inhibitory and stimulatory effects
Favors fibrogenesis during wound repair
MOST IMPORTANT: Growth factor responsible for repair by connective tissue/healing
Describe Histamine's location, function, and properties for release
Preformed substance found in: Mast cells, basophils, platelets
Vasodilation of arterioles
Increases permeability of venules
Released due to: Physical injury, IgE, C3a/C4a, IL-1, PLT aggregation,...
Describe Serotonin's location, function, and properties for release
Found in: Platelets and enterochromaffin cells
Vasodilation of arterioles
Increased permeability of venules
Released due to: Physical injury, IgE, C3a/C4a, IL-1, PLT aggretation,...
Describe Leukocyte adhesion deficiency Type I and Type II
Type I: Defect in biosynthese of B2 (No firm adhesion form VCAM-1 or ICAM-1)
Type II: Absence of sialylated oligosaccharides receptor for E and P selectins (No Rolling/Loose Adhesion)
Describe the genetic representation of Chronic Granulomatous Disease and what happens?
X-Linked (Defect in membrane NADPH - No oxidative "Burst")
Autosomal Recessive (defect in cytoplasmic NADPH oxidase
Common to get infections
Describe the genetic representation of myloperoxidase deficiency (MPO-Deficiency) and what happens
Absent MPO-H2O2 system (No oxidative "Burst")
Most common Neutrophil Defect
Common to acquire infections
Describe the genetic representation of Chediak-Higashi Syndrome and what happens
Autosomal recessive
Lysosomes cannot fuse w/ phagosomes
Lysosomes become large (No phagocytosis)
Neutropenia, albinism, nerve defects, bleeding, and Immunodeficiency
Common to acquire infections
Define Sinus tract and the following exudates: serous, fibrinous, Catarrhal, purulent/suppurative, hemmorhagic, and fibrinopurulent.
Sinus Tract: Passage or path formed by discharge of a deep abscess to the surface of skin or a mucosal membrane
Serous - serum like exudate
Fibrinous - fibrin rich exudate
Catarrhal - exudate from mucous membranes
purulent/supperative - leukocyte rich exudate
hemmorrhagic - bloody exudate
fibrinopurulent - inflammatory edema fluid containing puss and fibrin
Describe Local Anaphylaxis and give some examples
Localized reactions ot allergens
e.g. hayfever (Allergic Rhinitis), Urticaria (hives), Asthma, and Angioedema (recurrent large circumscribed areas of subcutaneous edema of sudden onset, usually disappearing within 24 hours.)
Describe systemic anaphylaxis
Characterized by vascular shock, widespread edema and difficulty breathing
What is Kernicterus and what are the characteristics of it?
Condition that occurs in premature infants which involves the movement of bilirubin into the brain due to incomplete formation fo the blood brain barrier.
Caused by deposition of bilirubin which causes destruciton of the basal ganglia and thalamus, leading to irreversible neurologic abnormalities
What is Acid hematin?
Formed when gastric acid mixes with blood
Pigment look like coffee grinds
Seen in the vomit of individuals with bleeding peptic ulcers
What is Hemochromotosis
Disease characterized by hemosiderosis
Frequently a genetic disorder
Massive accumulation of hemosiderin in hepatic and pancreatic parenchymal cells, myocardium and other sites
(Classic triad of cirrhosis, diabetes mellitus, and increased skin pigmentation.
Patients have bronze pigmentation due to melanocyt hyperplasia)
In hemochromotosis what is the classic triad?
Cirrhosis
Diabetes Mellitus
Increased skin pigmentation
What is Hematoidin?
Closely related to bilirubin
Does not contain iron (So it doesn't not stain with potassium ferrocyanide)
Found in infarcted areas, such as a splenic infarct
Appears as a "Sunburst" (Golden crystalline pigment)
What is a Psommoma body?
Seen in certain types of neoplasms
Calcification of a single necrotic cell
What is a Russell Body
Granules of immunoglobulins within plasma cells
What is hyaline?
Descriptive term for any material that is microscopically eosinophilic, refractive, glassy looking and amorphous
What is Goodpasture syndrome (Anti-GBM disease) and name its hypersensitivity?
Antibodeis against non-collagenous protein in the basement membrane of kidney glomeruli and lung alveoli
Hypersensitivity Type II
What is Bullous Pemphigoid and what is the hypersensitivity associated?
Skin disease that have antibodies that attach to the subepidermal-epidermal interface
Bulla is like large fluid-filled blloon tha toccurs in clumps about half a cm large.
Skin practically sloughs off
Type II Hypersensitivity
What is pernicious anemia and its associated hypersensitivity?
Antibodies against intrinsic factor decreaseing vitamin B12 absorption
Type II
What is sjogren sysndrome
Keratoconjunctivitis Sicca (dry eyes) and xerostomia (dry mouth)
Immunological destruciton of lacrimal and salivary glands
What is Systemic Sclerosis?
Abnormal accumulation of fibrous tissue
Skin hardening and increase in dermal collagen
Affects muscular motility in esophagus
Vascular diseaes, causes thickening of media vessels
Patients die of renal failure, malnutrition, or infection
What is dermatomyositis/Polymyositis?
Disorder of the skin and skeletal muscles characterized by skin rash and muscle weakness
(Polymyositis is similar does not involve skin)
What is mixed connective tissue disease
Features of rheumatoid, scleroderma, and lupus
What is rheumatoid arthritis
Antibodies against an antigen in the joint synovium
What is polyarteritis Nodosa
Antibodies against media walls of vessels
Describe the primary immunodeficiency Bruton (X-linked) agammaglobulinemia
Failure of B-cells precursers ot mature into b-cells therefore make no antibodies.
Patients can get periodic gammaglobulin injections containing antibodies from othe rpeople or get bone marrow transplant.
What is Isolated IgA primary immunodeficiency?
Don't have the gene to make IgA molecule
Secrety protection is compromised
Most common with 1 in 500
What is Severe combined immunodeficiency (SCID)a primary immunodeficiency
defect in humoral nad cell mediated immune responses
Two types:
X-linked
Autosomal Recessive (Adenosine deaminase deficiency)
What is pleomorphism?
Variation in size and shapes of cell as well as staining intensity
What are the carcinogens and what kind of cancer do they cause?
Benzanthracene (skin cancer, sarcomas).
Benzopyrene in tobacco smoke (lung cancer).
Beta-naphthalamine (bladder cancer)
Nitrosamines (gastric cancer).
Nitroso compounds in tobacco smoke (lung cancer).
Asbestos (lung cancer, mesothelioma).
Vinyl chloride (hemangiosarcoma of liver).
Arsenic (skin cancer).
Chromium, nickel, other metal (lung cancer).
Aflatoxin (Liver cancer).
What do oncogenes code for?
Growth Factors (sis)
Growth Factor Receptors(erb)
Signal Transucing Proteins (ras)
Nuclear Regulatory Proteins (myc)
What is Li-Fraumeni syndrome?
Inherited mutant copy of p53
What is Cushing's Disease?
hypercortisolism secondary to excess production of adrenocorticotropin (ACTH) from a pituitary gland adenoma.
What are the characteristics of Cachexia?
Loss of body fat
Loss of lean body mass
Profound weakness
Anorexia
Anemia
What are the characteristics of paraneoplastic syndromes and some examples?
Fever of unknown origin:
Lymphomas (especially Hodgkin's disease), renal carcinoma, osteogenic sarcoma.
Endocrine Syndromes:
Cushing's Syndrome (due to ACTH) - small cell (oat cell) carcinoma of lung.
Hyponatremia ( ADH)
Small cell carcinoma of lung.
Hypercalcemia ( PTH)
Squamous cell carcinoma of lung, breast and renal carcinoma.
Name some other examples of paraneoplastic syndromes
Hypoglycemia: Sarcomas, liver cancer
Carcinoid Syndrome: (Serotonin, histamine, bradykinin)
Bronchial carcinoid,
Metastatic carcinoid to liver.
Polycythemia: (Erythropoietin)Renal cell carcinoma
Neurologic and Muscle Syndromes, Peripheral neuropathy, Dermatomyositis, Polymyositis: Small cell carcinoma of lung
Myasthenia Gravis: Thymoma
Acanthosis nigricans: Gastroentestinal cancer
Clubbing of fingers,
Hypertrophic osteoarthropathy: Lung cancer
Migratory thrombophlebitis,
Deep vein thrombosis: Pancreatic cancer, GI tract cancer, lung cancer.
How do you calculate HDL ratio?
LDL/HDL
Can you calculate VLDL or do you measure it?
You calculate for it based on the triglyceride levels
What is the objective of the Atkins diet and what does that have to do with cholesterol levels?
Nothing to do with cholesterol.
Atkins targes slimness irrespective of cholesterol because obesity is correlated to mortality
How do you calculate BMI?
Body weight in kg / height in meters squared
How does being morbidly obese affect mortality ratio?
It doubles it by increasing the amount of health problems
It indicates that a person who is more obese at a younger age will have lost more years to their life than an older person
What does the trend of life chart indicate with regards to younger more obese individuals?
What does metabolic syndrome mean and name three of the things requred to be part of that group
Insulin resistance syndrome
Defined by:
Fasting glucose > 110 mg/dl (insulin resistance)
Abdominal obesity (waist girth > 102 cm i.e. 40 inches)
Serum triglycerides > 150 mg/dl
Serum HDL-cholesterol < 40 mg/dl
Blood pressure > 130/85 mm Hg
What are two procedures of bariatric surgery?
Rous en-Y gastric bypass
Vertical Banded Gastroplasty
What is Rous en-Y gastric bypass?
Stomach is taken ouf of loop so food never gets into stomach
Little bit of stomach is left to anastomose the jejunum up to the esophagus which brings food straight from esophagus to jejunum other arm of Y carries bile and pancreatic juices
What is Vertical banded gastroplasty?
"stomach stapling"
stomach remains in loop but there is a constriction, which slows flowing of food into stomach
The constriction is made by using a staple with a band around it to prevent it from opening over time
What is glycemic index and how do you measure it?
It is a ratio of the glucose tolerance curve
Demonstrates how different carbohydrates affect glucose levels
Measured by taking:
Area under experimental (Carbohydrate) curve / Area under baseline (glucose) curve
Can a high glycemic index food be lowered during consumption?
yes. If the starches are eaten with somehting else the glycemic index can be reduced
What is the reasoning for low glycemic index foods causing a decrease in appetites yielding less obesity?
whole grain foods and low glycaemic index foods are emerging as dietary constituents that appear to reduce the likelihood of disease complications by reducing risk factors for the insulin-resistant diseases...A reason for the effects...Is evidently based on slowing the rate of absorption and creating a late reservoir in the small intestine..
What does Glucagon-like Peptide 1 (GPL-1) do and where does it come from?
released by the small intestines when there are carbohydrates being absorbed to suppress apetite
What effects does obesity have on health issues?
Knee osteoarthritis, since it adds more weight to be supported
MORBIDLY obese, there is an increase incidence of hip replacement
What is Marasmus?
Malnutrition caused by severe reduction in caloric intake
Greater than 60% reduction in body weight adjusted for height and weight
Child shows growth retardation and loss of muscle
Chronic illness occurring over months
Waht is Kwashiokor?
protein deprivation greater than the reduction in total calories
Marked protein deprivation associated with severe loss of visceral protein compartment
weight is generally 60-80% of of normal weight for their age
Acute illness occurring over weeks
What is Pellagra?
Deficiency of niacin or tryptophan
Among alcoholics and persns suffereing from chronic dehabilitiating disease (such as HIV)
Causes 3 D's (Diarrhea, dermatitis, and dementia)
What is Beriberi?
Deficiency in thiamine
Associated with peripheral vasodilation, leading to more rapid arteriovenous shunting of blood, high-output cardiac failure and eventually, peripheral edema
What is Niacin
I can't believe you are trying to answer this question! Fine!
It is a generic designation for nicotinic acid.
Plays central role in dehydrogenase reactions, particularly hexose-monophosphate reaction
What is Thiamine?
Again??
Vitamin in the diet found in such refined foods as polished rice, white flour and white sugar contain little
Regulate oxidative decarboxylation of alph-keto acids, leading ot synthesis of ATP
What is protein-energy malnutrition (PEM)
Clinical syndromes characterized by an inadequate dietary intake of protein and calories to meet the body's needs
What is somatic protein
one of the two protein compartments in the body, which is represented by skeletal muscle
What is Visceral protein
Other protein compartment represented by protien stores in visceral organs, primarily the liver
What causes neural tube defects?
Folic acid lack during pregnancy (essential cofactor in nucleic acid synthesis)
What is Rickets
deficiency in Vitamin D in growing children
Overproduction and deficient in calcification of osteeoid bone
Associated skeletal abnormalities
Disturbances in growth
Hypocalcemia
What is proband?
Patient who is affected in a pedigree
What are the two most common causes of death (They are genetic disorders)?
Cardiovascular disease
Cancer
What are the characteristics of Mendelian Disorders?
Imply involvement of single gene
Imply mutation of the gene
Display characteristic family pedigrees and inheritance patterns
More than 5000 described diseases
Everyone carries 5-8 abnormal genes
What is reduced penetrance?
Abnormal gene but you don't display the diesease phenotypically
What is Variable expressivity?
Abnormal gene manifests itself differently into varying severies in each person
what are three questions to ask in analysis of inheritence patterns?
Are both males and females affected?
Is every generation involved?
Is there male to male transmission?
Based on the three questions of determining inheritence patterns what would be the answers for an Autosomal Dominant?
Are both males and females affected? Yes
Is every generation involved? Yes
Is there male to male transmission? Yes
Based on the three questions of determining inheritence patterns what would be the answers for an Autosomal Recessive?
Are both males and females affected? Yes
Is every generation involved? No
Is there male to male transmission? Unknown
Based on the three questions of determining inheritence patterns what would be the answers for an X-Linked Dominant?
Are both males and females affected? Yes
Is every generation involved? Yes
Is there male to male transmission? No
Based on the three questions of determining inheritence patterns what would be the answers for an X-Linked Recessive?
Are both males and females affected? No
Is every generation involved? Yes
Is there male to male transmission? No
What is the pattern of inheritence for an Autosomal Dominant?
Males = Females
Disease appears in every generation
No carrier state (Have it or not)
Recurrrence risk is 50%
What are the characteristics of Marfan syndrome?
Skeletal: Disproportionate (Key) tall stature, arachnodactyly, pectus excavatum
Ocular: myopia, upwards lens dislocation
CVS: mitral valve prolapse, thoracic aortic root aneurysm / dissection
1/5000
Fibrillin-1 gene (chrom 15)
> 500 types of mutations(missense= #1)
30% are new mutations
AUTOSOMAL DOMINANT
What are the characteristics of neurofibromatosis-1 (NF1)?
Skin: Café au laits (>6), axillary freckling, neurofibromas
Eyes: Lisch nodules, optic glioma
Neuro: Learning disability
Rare: cancer, HTN,pheochromocytoma
1/3000
Neurofibromin gene (chrom 17), a tumor suppressor gene 50% are new mutations
AUTOSOMAL DOMINANT
What are the characteristics of Ehlers-Danlos syndrome?
AUTOSOMAL DOMINANT
> 5 variants
Skin: hyperextensible, keloids
Joints: hypermobile Artery and viscera rupture (Type IV)
Retinal detachment (Type VI)
Diaphragmatic hernia (Type I)
Genetic heterogeneity: mutations at several loci (genes) produce same trait
Collagen genes (type I-IV); autosomal dominant
Lysyl hydroxylase gene (type VI); autosomal recessive
What are the characteristics of Familial Hypercholesterolemia?
AUTOSOMAL DOMINANT
Most common Mendelian disorder
3-6% of MI survivors
1/500
LDL receptor gene (chrom 19)->900 different mutations (deletions, point mutations)
What are the characteristics of adult polycystic kidney disease?
AUTOSOMAL DOMINANT
Large kidneys with multiple, bilateral cysts
Renal failure in 50s
40%: hepatic cysts or berry aneurysms (cause 10% of APCKD deaths)
25% with heart defects (MVP)
1/600
5-10% of chronic renal failure
Genetic heterogeneity: PKD1 gene (85%)(chrom 16);
PKD2 gene (15%)(chrom 4)
What are the characteristics of tuberous Sclerosis Disorder?
AUTOSOMAL DOMINANT
Tubers’ (tumors) of: brain, kidney, eye, heart, fingernails
Skin: hypopigmented patches
CNS: mental deficiency, seizures
Genetic heterogeneity:
Tuberin gene (chrom 16)
Hamartin gene (chrom 9)
What are the characteristics of Autosomal Recessive Diseases?
Manifests in homozygous state
Heterozygotes are carriers and unaffected
Classically congenital or early-onset diseases
Involves defective enzymes
Does not display variable expressivity, reduced penetrance, or new mutation phenomena
What is the inheritance pattern of Autosomal Recessive?
Males=Females
Appears only in siblings of
same generation
Higher likelihood of consanguinity
Recurrence risk is 25% for carrier parents
What are the characteristics of tyrosine negative albinism?
Autosomal RECESSIVE
Little pigmentation in skin, hair and eyes
Nystagmus or strabismus
Tyrosinase gene mutation (chrom 11)
Results in decreased melanin
What are the characteristics of PKU?
Autosomal RECESSIVE
Fair pigmented
“Mousy” odor at birth
Untreated: mental retardation, seizures, paraplegia
Treated: relatively normal.
1/10,000 whites
Phenylalanine hydroxylase gene(chrom 12)
The prototype for the newborn screening program

Treatment: severe dietary restriction of phenylalanine

“Congenital PKU”: a teratogenic, neonatal disease That only occurs when mom has PKU. Not inherited
What are the characteristics of Sickle Cell Anemia?
Autosomal RECESSIVE
Anemia
Vasoocclusive crises in bones, lungs, brain
Pain crises
Priapism
Autosplenectomy and infections
Howell Jolly bodies
Sickled RBCs (drepanocytes)
globin gene mutation (chrom 11)
Missense mutation: glutamine to valine
1/14 blacks are carriers
Carriers resistant to malaria
What are the characteristics of Cystic Fibrosis?
Autosomal RECESSIVE
Recurrent infections, cirrhosis, diabetes, pancreatic insufficiency, bronchiectasis
Death in 20s
Most common lethal genetic
disease of Caucasians
1/3200 Caucasians
Chloride channel gene mutation (chrom. 7)
1/22 caucasians are carriers
What are some characteristics of Lysosomal Storage Diseases?
Involve the lysosomal enzymes that are responsible for breakdown of complex molecules
Without normal breakdown, the molecule is trapped or stored inside the lysosome
Disease is classified according to the nature of the accumulated metabolite:
Glycogenoses
Sphingolipidoses
Sulfatidoses
Mucopolysaccharidoses
AUTOSOMAL RECESSIVE
What are some examples of Lysosomal Storage Diseases?
Glycogenoses:
Disease: Pompe
Sphingolipidoses:
Disease: Tay Sachs
Sulfatidoses:
Diseases: Gaucher
Niemann-Pick
Mucopolysaccharidoses:
Diseases:
Hurler (type I)
Hunter (type II)
What are some characterisitcs of Tay Sachs Disease (Sphingolipidoses)?
Autosomal RECESSIVE
Begins at 6months
Progressive blindness (cherry red retinal spot),
seizures, mental retardation
Death at 2-3 yrs
Hexosaminidase A gene
(chrom.15) (4bp insertion mutation)
1/27 Ashkenazi Jews are carriers.
What are some characteristics of Gaucher's Disease (Sulfatidosis)?
Type I (99%): adults, splenomegaly, bone pain and fractures
Type II: infants, hepatosplenomegaly, seizures, mental retardation and early death
Type III: juvenile form, intermediate prognosis
'Crumpled tissue paper’ cell
Most common LSD
Glucocerebrosidase gene (chrom 1)
> 150 mutations identified
What are the characteristics of Neiman-Pick Disease (sulfatidosis)?
Autosomal Recessive
Type A: infants, hepatosplenomegaly, vomiting, mental retardation and death by 2years old
Type B: intermediate form
Type C: Most common form; childhood, ataxia, hepatosplenomegaly, retardation and hepatitis
NPC vacuolated cell filled with fat
Sphingomyelinase gene (chrom 11)
What are the characteristics of Hunter's and Hurler's Syndromes?
Autosomal Recessive
6 subtypes of MPS
Hurler syndrome (MPSI): severe, hepatosplenomegaly, coarse facies, mental and growth retardation, corneal clouding, death by 10yrs due to ‘coronary artery disease’
Hunter syndrome (MPSII): milder, no corneal clouding,
Iduronidase genes
MPS I is autosomal recessive (chrom 4)
MPS II is X-linked
What are some examples of other autosomal recessive Disorders?
Thalessemia
Usher Syndrome: Deafness and blindness
Zellweger Syndrome: Hepatorenal involvement with an abnormal face
What are some examples of other autosomal dominant disorders?
Achondroplasia: Dwarfism
Huntington's Disease: choreiform movements, adult onset
Osteogenesis Imperfecta
Apert Syndrome: Craniosynostosis 9Fused sutures in the head), hand and feet anomalies
What are the characteristics of X-Linked Dominance?
Very rare
Female manifests as heterozygote
Male may be severely affected; potentially incompatible with life (male lethality phenomenon)
Clue is a female with multiple stillbirths/ miscarriages (decreased fertility phenomenon)
What are some additional features of X-linked Dominant?
Females > Males ( 2:1 )
Males may have lethal form
No Father-to-Son transmission
Recurrence risk for affected male:
100% for daughters
0% for sons
Recurrence risk for affected female:
50%
Males=females
What are the characteristics of Incontinentia Pigmenti?
X-Linked Dominant
Abnormal skin pigmentation
Conical or missing teeth
Ocular
Neurologic
Seen only in females
Heterozygote females only mildly affected
Affected females have many SABs
What are the features of X-Linked Recessive individuals?
Males >> Females
Males are hemizygous
No Father- to - Son transmission
Carrier females have variable expression
Recurrence risk for affected male:
0% affected
100% daughters are carriers
Recurrence risk for carrier female:
50% sons are affected
What are the characteristics of Duchenne's Muscular Dystrophy?
X-Linked RECESSIVE
Progressive weakness and muscle atrophy
Pseudohypertrophy of calf muscles
Wheelchair by age 11
Death by age 25 due to respiratory and cardiac failure
1/3500 males
Dystrophin gene mutations
Deletions most common
1/3 are new mutations
Carrier females may be mildly affected (cardiac mm.)
What are the characteristics of G6PD?
X-Linked Recessive
Hemolytic anemia in response to drugs, infections, foods
Anemia is self-limited
G6P dehydrogenase gene
What are the characteristics of Hemophilia?
X-Linked Recessive
Easy bruising, hemorrhage, hemarthroses
Subtype A worse than B
Genetics
Type A: factor VIII gene
Type B: factor IX gene
1/3 are new mutations
Females at risk for mild bleeding tendency
What are the parameters of Balanced Structural Chromosomal Abnormatlities?
Correct amount of DNA (2n or diploid)
DNA is stored in a rearranged fashion
Correct number of chromosomes (46) may or may not be present
Affected individuals are normal but their offspring are at risk for abnormalities
Examples:
Inversions
Translocations
In Inversion Balanced Chromosomal Abnormalities what are the various types?
Paracentral: Segment of One arm of a chromosome has been inverted (Does NOT include the centromere)
PerIcentral: Segment of one chromosome INCLUDING the centromere has been inverted
In Translocation Balanced Chomosomal Abnormalities what are the various types?
Reciprocal Translocation: Swap of information between two chromosomes - between non homologous pairs
Occurs in 1/600 cases
Not problem if all DNA there
Robertsonian translocation:
Fusion of two chromosomes
Result total 45 Chromosome
Balanced - individual is normal
Typically they are Acrocentric chromosomes (Having centromere close to one end; said of a normal chromosome)
1/1300
Most common t(13;14)
What are the two types of balanced chromosomal abnormalities?
Inversion and Translocations
What are the characteristics of an unbalanced cytogenetics arrangements?
Wrong amount of DNA is present
Correct number of chromosomes may or may not be present
Affected individuals are abnormal, the severity of which depends on the size of the abnormal component
Examples:
Deletions
Duplications
Isochromosomes
Translocations
What are the characteristics of Deletion from unbalanced Disorders?
Chromosomal material is lost between breakpoints
1/7000 live births
Type = Ring chromosome
when two broken ends anneal to form a ring; leaving behind two fragments that are deleted
Given these characteristics:
microcephaly, hypertelorism,
epicanthal folds, mental retardation, and a high pitched cry
what is the diagnosis and some descriptions about it?
Cri Du Chat
del(5p15)
1% of institutionalized patients
90% sporadic (de novo)
10% inherited from a parent
who carries a balanced
translocation or who is
affected
Given these Characteristics:
hypertelorism, down slanting
palpebral fissures, prominent nose, parathyroid
hypoplasia with hypocalcemia, thymic
hypoplasia with immunodeficiency, congenital
heart defect
What is the diagnosis and some associated features?
DiGeorge's Syndrome
del(22q11)
20% of ‘conotruncal heart defect’ patients
1/3000 live births
90% are sporadic (de novo)10% are inherited from a balanced
translocation parent or one who is affected
Given these characteristics:
distal muscle weakness, foot drop, ‘stork legs’, flat feet, muscle wasting, hand weakness
what is the diagnosis and some associated features?
Charcot Marie Tooth Disease
dup(17p11.2)
1/2500
Majority are inherited from an affected parent
What is an isochromosome?
involve loss of one arm of chromosome with duplication of the other arm
Given these characteristics:
short stature, webbed neck, wide spaced nipples, increased carrying angle, coarctation of the aorta
What is the diagnosis and associated features?
Turner Syndrome
1/2500 live birth females
>99% are miscarried
50% have only one X chromosome
15% due to i(Xq)
(so that Xq is duplicated; and Xp is deleted)
What is Translocation?
involve two chromosomes exchanging information
ex. Reciprocal and Robertsonian
What is the definition of polyploidy?
Abnormal Multiple of 23: 69 (triploidy) or 92 (tetraploidy)
Triploidy (69,XXX)
1/10,000 livebirths
Lethal
Usually due to dispermy
Given the characteristics:
Newborn born alive and quickly died with low apgar scores. could not resuscitate. Very small for gestational agae. very dysmorphic. very abnormal cardiac defect. Child has (see figure).
What is the diagnosis and associated features?
What is the definition of aneuploidy?
One missing or extra chromosome (45 or 47)
Aneuploidy
Trisomy 21 (down's Syndrome)
1/800 livebirths
95% due to true trisomy
Risk increases with maternal age
5% due to translocations
Given the Characteristics:
dysmorphic face, duodenal atresia, mental retardation, hypotonia, leukemia, heart defect
What is the diagnosis and associated features?
Aneuploidy
Trisomy 18
a.k.a Edwards Syndrome
1/8000 livebirths
80% due to true trisomy
Risk increases with maternal age
20% due to unbalanced translocations
Given these characteristics:
hand clench, omphalocele, heart defects, mental retardation, rocker bottom feet, horseshoe kidneys
What is the diagnosis and the associated features?
Aneuploidy: Trisomy 13
a.k.a. Patau Syndrome
1/15,000 livebirths
80% due to true trisomy
Incidence increases with maternal age
20% due to unbalanced translocation
Given these characteristics:
midline defects (cyclopia, holoprosencephaly, heart defects, cleft lip, neural tube defects, polydactyly
What is the diagnosis and associated features?
Aneuploidy: Monosomy X
a.k.a. Turner Syndrome
1/2500 livebirth females
>99% miscarry in utero
50% due to monosomy X (45,X)
50% due to other: i(Xq); mosaicism
Given the Characteristics:
short stature, webbed neck, shield chest, ovarian dysgenesis, coarctation of aorta
What is the diagnosis and associated features?
Aneuploidy: 47, XXY
Klinefelter Syndrome
1/850 livebirth males
85% due to aneuploidy: 47, XXY
More often due to paternal meiosis problem
Risk increase with advancing maternal age
15% are mosaic
Given the characteristics:
Hypogonadism, Infertility, Tall stature, Gynecomastia
What is the diagnosis and associated features?
Describe aneuploidy 47, XYY
a.k.a. the SuperMale:
Incidence: 1/ 1000 livebirth males
Due to paternal meiotic nondisjunction
Features: tall stature, increased behavioral problems
No increased risk for psychopathology
Describe aneuploidy trisomy X (47,XXX)
a.k.a. the SuperFemale
Incidence: 1/1000 livebirth females
Due to maternal meiotic nondisjunction
Features: increased behavioral/ learning problems
What are some cancers related to smoking both major causes and contirbutory factors?
Major cause:
Lung, larynx, oral, cavity, esophagus
Contirbutory factor:
Pancrease, bladder, Kidney, stomach, uterine cervix
What are some alcohol reltated cancers?
Esophageal
Head and neck
liver
breasts