• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/90

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

90 Cards in this Set

  • Front
  • Back
Leukocyte Adhesion Deficiency Type I
Defect in biosynthesis of B2 integrins

B-2 integrins bind to ICAM -1

causes firm adhesion deficiency

results in impaired leukocyte activation and recurrent bacterial infections

Diagnosed by flow cytometry
Leukocyte Adhesion Deficiency Type 2
absence of sialyated oligosacch. receptor for endothelial cell selectins

causes a deficiency in rolling

results in impaired leukocyte activation and recurrent bacterial infections

diagnosed by flow cytometry
Exogenous Chemoattractants
soluble bacterial products

N-formly methionine terminal amino acids
Endogenous chemoattractants
Complement metabolites (c5a)

AA metabolites (leukotriene B4)

Cytokines (Il-8)
Chronic Granulomatous Disease
X-Linked
defect in membrane NADPH oxidase

CGD results in recurrent bacterial infections, especially catalase positive bacteria

Diagnosis: Nitroblue tetrazolium (NBT) test
-testing capacity of neutrophils to reduce NBT to formazan yielding a blue pigment
-In CGD, no blue pigment is identified
Chronic Granulomatous Disease
Autosomal recessive
defect in cytoplasmic NADPH oxidase
AC= air conditioner

Diagnosis: Nitroblue tetrazolium (NBT) test
-testing capacity of neutrophils to reduce NBT to formazan yielding a blue pigment
-In CGD, no blue pigment is identified
Myeloperoxidase Deficiency
Absent H2O2-MPO system

most common neutrophil defect

Recurrent bacterial infections
Chediak-Higashi Syndrome
1. Autosomal recessive

2. Lysosomes cannot fuse phagosome , thus they become giant-sized

3. Results in neutropenia, recurrent infections, defective degranulation, problems with migration and chemotaxis

4. Some clinical features include albinism, nerve defects, bleeding, immunodeficiency due to defects in organelle membrane fusion
Cellulitis
spreading of inflammation in a solid tissue
Ulcer
localized defect in the surface of an organ or tissue due to sloughing of inflammatory necrotic debris
Paroxysmal nocturnal hemoglobinuria (PNH)
Deficiency of DAF → Intravascular hemolysis/anemia
Hereditary angioneurotic edema (HAE)
Deficiency of C1 inhibitor

1. Swelling of skin, larynx, intestines
2. Stress, trauma
Epidermal Derived growth factor (EGF)
mitogenic (stimulates mitosis) for a variety of epithelial cells and fibroblasts

causes hepatic cell division in vivo

TGF alpha binds to the same receptors and produces the same effects
Platelet Derived growth factor
stored in alpha granules of platelet cells

causes migration and proliferation of
1. fibroblasts
2. smooth muscle
3. monocytes

produced by:
1. activated macrophages
2. endothelial cells
3. smooth muscle cells
4. many tumor cells
Fibroblast growth factor
causes angiogenesis

development

hematopoisesis
Vascular endothelial growth factor
vascular permeability factor

vasculogenesis
angiogenesis
Migration and proliferation of fibroblasts
TGF-beta
PDGF
EGF
FGF
IL-1
TNF - alpha
Deposition of ECM
VEGF
FGF
Collagen synthesis
PDGF
FGF
TGF-B
IL-1 and IL-4
Benzanthracine
skin cancer
sarcomas
Benzopyrene in tobacco smoke
lung cancer
beta-napthalamine
bladder cancer
nitrosamine
gastric cancer
nitroso compounds in tobacco smoke
lung cancer
asbestos
lung cancer
mesothelioma - malignant tumor of the pleura
Vinyl Chloride
hemangiosarcoma of the liver
arsenic
skin cancer
chromium, nickel, or other heavy metals
lung cancer
aflatoxin
liver cancer
Hepatitis B and C
hepatocellular carcinoma
epstein-barr virus
burkitt's lymphoma
nasopharyngeal carcinoma
Herpes Virus type II
warts
cervical cancer
HPV
warts
cervical cancer
HTLV-1
adult T-cell Leukemia/lymphoma
HIV -1
Kaposi's Sarcoma
UV rays
squamous cell carcinoma
basal cell carcinoma
malignant melanoma
X-Rays
skin cancer
bone cancer
miners of radioactive elements
lung cancer
atom bomb radiation
leukemia
theraputic radiation to the head and neck
thyroid cancer

former treatment for acute tonsillitis
thorium
liver cancer

formerly used as a contrast medium
Li-Fraumeni syndrome
inherited mutant p53

predisposes to a wide range of tumors
Chronic myelgenous leukemia (CML)
translocation 9:22
Burkitt's lymphoma
translocation 8:14
Retinoblastoma
deletion 13
Wilm's tumor
deletion 11
neuroblastoma
N-myc gene amplification
Carcinoembryonic Ag (CEA)
colorectal, pancreatic, liver, gastic cancers
Alpha-fetoprotein (AFP)
liver cancer, germ line tumors of testis
Prostatic Specific Ag (PSA)
Prostatic Acid Phosphatase (PAP)
prostate cancer
Human Chorionic Gonadotropin (HCG)
trophoblastic tumors, germ cell tumors
Carcinoma of the Lung
1. Local Growth & Extension: encircle bronchus, extend to esophagus, parietal pleura, brachial plexus, mediastinum

2. Implantation: pleura seeding and effusion

3. Metastasis:
a. Lymphatic: tracheobronchial, mediastinal, scalene nodes
b. Hematogenous: adrenal/bone (common); liver, kidney, brain
Carcinoma of Colon & Rectum
1. Local Growth & Extension: fungating, ulcerative or stenotic; extend to serosa and nearby organs
a. Right-sided: usually large fungating masses
b. Left-sided: usually stenotic (apple-core lesions)
c. Common Presentation: alternating diarrhea and constipation

2. Implantation: peritoneal seeding after extension through serosa

3. Metastasis:
a. Lymphatic: mesenteric nodes
b. Hematogenous: liver via portal system; can then affect lung
Carcinoma of the Breast
1. Local Growth & Extension: hard scirrhous or bulky soft medullary mass; may have intra-epidermal extension; nipple inversion, peau d’orange (due to blocked lymphatics)
a. Hard Scirrhous: desmoplastic adenocarcinomas
b. Bulky Soft: medullary carcinomas

2. Metastasis:
a. Lymphatic: axillary, internal mammary, supraclavicular nodes; opposite breast
b. Hematogenous: lung, liver, bone, adrenal, ovary, brain
Carcinoma of the Prostate
1. Local Growth & Extension: stony hard mass on posterior lobe; extend to: seminal vesicles, bladder base, rectum, urethra

2. Metastasis:
a. Lymphatic: pelvic, periaortic nodes
b. Hematogenous: bone- osteoblastic (*unusual- most lesions are osteolytic*); lung, testis, adrenal
Carcinoma of the Cervix
1. Local Growth & Extension: vaginal wall, ureters, urinary bladder
a. Can lead to: urethral obstruction, pyelonephritis, uremia (renal failure is common cause of death)

2. Metastasis:
a. Lymphatic: regional lymph nodes
Epithelial
(tumor Marker in tissue)
keratin
epithelial membrane Ag (EMA)
Carcinoembryonic Ag (CEA)
Mesenchymal
(tumor Marker in tissue)
vimentin
desmin
Nerve, Neuroendocrine
(tumor Marker in tissue)
Neuron specific enolase (NSE)
chromogranins
Prostate
(tumor Marker in tissue)
Prostate specific Ag (PSA)
Prostatic Acid phosphatase (PAP)
Lymphomas
(tumor Marker in tissue)
Leukocyte common Ag (LCA
T and B cell markers
Endocrine
(tumor Marker in tissue)
hormones
Carcinoembryonic Ag (CEA)
(tumor Marker in blood)
Colorectal
pancreatic
liver
gastric cancers
Alpha fetoprotein (AFP)
(tumor Marker in blood)
liver cancer
germlkine tumors of testis
PSA
PAP
(tumor Marker in blood)
prostate cancer
HCG
(tumor Marker in blood)
trophoblastic tumors
germ cell tumors
Marfan Syndrome
A connective tissue disorder

Autosomal Dominant

Features
1. very tall thin patient
2. Disproportionate tall stature
3. Arachnodactyly
4. Pectus excavatum - dent in chest
5. myopia (near sightedness)
6. upward lens dislocation
7. Mitral valve prolapse
8. thoracic aortic root dilates and dissects

Genetics
1. 30% new mutations
2. Fibrillin gene defect
3. incidence 1/5000


pectus excavatum
Neurofibromatosis Type 1 (NF1)
Autosomal dominant

Features
1. Skin: Café au laits (more than 6), axillary freckling (most people shouldn’t have these), neurofibromas (benign tumors)
2. Eyes: Lisch nodules (benign tumors), optic glioma (benign tumors on the optic nerve)
3. Neurological: may have Complex Learning disability (usually a visual-spatial disability… they are not mentally retarded)
4. Rare:
a. one of the benign tumors can transform into cancer, so follow the patient overtime
b. pheochromocytoma

C. Genetics:
1. incidence: 1/3000
2. Neurofibromin gene on chromosome 17; a tumor suppressor gene
NT note: the tumor suppressor gene is defective, therefore it is not “applying the brakes” to cellular proliferation, and multiple tumors are able to form, as in NF1.
3. 50% are new mutations
Ehlers-Danlos Syndromes
a group of connective tissue disorders

Autosomal Dominant

Types I through IV

Features:
1. Skin: hyperextensible, keloids (abnormal scar formation)
2. Joints: hypermobile
3. Artery and viscera rupture (Type IV) can be an immediate cause of death.
4. Retinal detachment (Type VI)
5. Diaphragmatic hernia (Type I)

1. Genetic heterogeneity: mutations at several loci (genes) produce same trait. In other words, several different gene mutations cause similar disorders
Familial Hypercholesterolemia
Autosomal Dominant

C. Features
1. These individuals have cholesterol levels 3 to 6 times the normal level.
2. Xanthomas, premature atherosclerosis
3. These individuals may have a myocardial infarct (MI) as early as 20 years of age.

Genetics
1. Most common Mendelian disorder
2. 3-6% of the survivors of myocardial infarctions have familial hypercholesterolemia.
3. Incidence: 1/500
4. LDL receptor gene on chromosome 19 is defective however there are over 900 different mutations including deletions and point mutations. Therefore, it is very difficult to diagnosis at the molecular level because you must know the specific mutation that you are looking for.
Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant

Features:
1. Large kidneys with multiple, bilateral cysts
2. Individuals end up in renal failure by the age of about 50.
3. 40% of the time the individuals have cyst in other organs or berry aneurysms. The classic example is hepatic cysts. (Common USMLE question).
4. Berry aneurysms are dilations in the anterior half of the Circle of Willis (right hand lower picture) These aneurysms cause 10% of adult polycystic kidney disease deaths.
5. 25% of the time there are heart defects; most commonly mitral valve prolapse.
6. Even though the name of the disorder “says” it’s a kidney disease, it’s a systemic disorder.

Genetics:
1. Incidence: 1/600; very common and you will definitely see it on the wards.
2. 5-10% of the individuals with chronic renal failure will have this disease
3. Genetic heterogeneity: The PKD1 gene on chromosome 16 is the mutation that causes the disease 85% of the time and the PKD2 gene chromosome 4 is the culprit 15% of the time. Remember, different mutations, same disorder.
Tuberous Sclerosis
Autosomal Dominant

B. Features
1. ‘Tubers’ (tumors) = fibromas in the brain, kidney, eye, heart & fingernails (seen in the top photo). These tumors can be passed off as warts and the diagnosis can be missed.
2. Skin: hypopigmented patches (seen in the bottom photo), “sort of the opposite of the café-au-lait”
3. CNS:
a. mental deficiency. Associated much more with mental retardation. Remember in NF1 the patients are not mentally retarded.
b. Classically presents with seizures.
C. Genetics
1. Genetic heterogeneity: Tuberin gene on chromosome 16 & Hamartin gene on chromosome 9.
2. Has variable expressivity = autosomal dominant trait is expressed differently in affected individuals
Achondroplasia
causes dwarfism
B.Huntington’s disease
Autosomal dominant

have choreiform movements, adult onset
C.Osteogenesis Imperfecta
broken bones all over the body
D.Apert Syndrome
Craniosynostosis (fused sutures in the head), hand & feet anomalies
XVIII. Tyrosinase-Negative Albinism
Autosomal Recessive

1. Little pigmentation in skin, hair and eyes
2. Nystagmus: rapid involuntary rhythmic eye movement
3. strabismus: “cross-eyed” (eyes do not point in the same direction)
C. Genetics: Tyrosinase gene mutation on chromosome 11 that results in decreased melanin
Phenylketonuria
Autosomal recessive

A. Features:
1. Fair pigmented
2. “Mousy” “attic-like” odor at birth
3. Overly attractive children, “cute cute cute cute kids” according to Dr. McGoey’s experience.
4. If left untreated, the child will develop mental retardation, seizures & paraplegia.
5. If treated the children are relatively normal.
a. Nationwide screenings for PKU are done (mandatory) for newborns a couple weeks after birth to avoid the severe neurological damage.

B. Treatment: a severe dietary restriction of phenylalanine

C. Genetics:
1. Incidence: 1/10,000 whites
2. Defect in the Phenylalanine hydroxylase gene on chromosme 12
XX. Sickle Cell Anemia
Autosomal Dominant

B. Clinical:
1. Anemia
2. Pain crises
3. Priapism – a sustained very painful erection can occur in a child.
3. Autosplenectomy and infections – spleen becomes infarcted due to vasoclussive crisis, therefore there is an increase likelihood of infections. Therefore vaccines are given to these individuals.

C. Morphologic Features: Howell Jolly bodies (purple things inside RBCs) & Sickled RBCs (drepanocytes)

D. Genetics: b globin gene mutation on chromosome 11; Missense mutation: glutamate to valine
XXI. Cystic Fibrosis
Autosomal recessive

failure to thrive, microcephaly, nasty sputum production & constantly on antibiotics due to recurring infections.

B. Features: Recurrent infections, cirrhosis, diabetes, pancreatic insufficiency, bronchiectasis (dilated bronchi seen in the top picture often filled with pus, infection, & mucus), death in 20s

C. Genetics:
1. Most common lethal genetic disease of Caucasians
2. Incidence: 1/3200 in Caucasians, 1/22 Caucasians are carriers
a. There is a movement to offer CF testing to all Caucasians thinking of becoming pregnant.

D. Chloride channel (CFTR) gene mutation on chromosome 7
XXII. Lysosomal Storage Diseases (LSDs)
Autosomal recessive

A. Involves the lysosomal enzymes that are responsible for the breakdown of complex molecules.

C. Lysosomes store things that they shouldn’t be storing.

D. Disease is classified according to the nature of the accumulated metabolite
1. Glycogenoses: Disease = Pompe (won’t discuss at present)
2. Sphingolipidoses: Disease = Tay Sachs, Gaucher, Neimann-Pick
3. Mucopolysaccharidoses Diseases: Hurler (type I) & Hunter (type II)
E. Sphingolipodosis LSD: Tay Sachs
Tay Sachs Disease

Features
1. progressive blindness
2. cherry red retinal spot seen via fundoscopic exam), --> not specifice but associated with it
3. decline in developmental milestones,
4. seizures,
5. mental retardation;
6. Death at 2-3 years

Genetics: Hexosaminidase A gene on chromosome
F. Sphingolipidosis LSD: Gaucher Disease
1. Clinical:
a. Type I (99%): adults, splenomegaly, bone pain and fractures
b. Type II: infants, hepatosplenomegaly, seizures, mental retardation and early death
c. Type III: juvenile form, intermediate prognosis
NT note: Just know that there are multiple types, do not memorize each type. .

2. Morphologic Feature: ‘Crumpled tissue paper’ cell

3. Genetics: Most common LSD; 1/15 Ashkenazi Jews are carriers for type I; More than 150 mutations identified of the Glucocerebrosidase gene on chromosome 1
G. Spingolipidosis LSD: Neimann-Pick Disease
1. Clinical:
a. Type A: infants, hepatosplenomegaly, vomiting, mental retardation and death by 2 years old. More common
b. Type B: intermediate form
c. Type C: Most common form; childhood, ataxia, hepatosplenomegaly, retardation and hepatitis

2. Morphologic feature: Neiman-Pick C (NPC) vacuolated cell (SLIDE 34) filled with microvesicular fat seen commonly in the liver and the spleen.

3. Genetics: Sphingomyelinase gene on chromosome 11; 1/1000 Ashkenazi Jews is carrier.
H.Mucopolysaccharidoses (MPSs) LSDs
1. 6 subtypes of mucopolysaccharidoses
2. 1/25,000 births
3. Hurler syndrome (MPS Type I): severe, hepatosplenomegaly, coarse facies, mental and growth retardation, corneal clouding, death by 10-15 years of age due to ‘coronary artery disease’
4. Hunter syndrome (MPS Type II): milder, no corneal clouding
5. Genetics: Iduronidase genes
a. MPS I is autosomal recessive with a mutation of the iduronidase gene on chromosome 4
b. MPS II is X-linked
NT Note: To help remember, Dr. McGoey suggested thinking Men like to Hunt more so Hunter’s is X-linked (men).
6. A student asked “Should these characteristics be present when they are very young or do they develop over time?” Dr. McGoey answered “Yes. You should see these characteristics the moment they are born. Even very experienced and practiced pediatricians miss the features, but they should be identifiable.”
XXIII. Other Autosomal Recessive Disorders
A. Thalessemias
B. Usher syndrome
1. huge population of Cajun individuals with this disorder in Louisiana; deafness and blindness
C. Zellweger Syndrome: hepatorenal involvement with an abnormal face
XXV. Incontinentia Pigmenti
X linked Dominant

A. Scenario: “beautiful swirling hyperpigmentation” patterns, teeth abnormalities, and ataxia.

B. Features: Abnormal skin pigmentation, Conical or missing teeth, Ocular, Neurologic, also can be mentally affected

C. Genetics: Seen only in females; Heterozygote females only mildly affected; Affected females have many SAB (spontaneous abortions)
Duchenne Muscular Dystrophy
X linked recessive

uses his hands to crawl up his legs (Gauer’s sign)

1. Progressive weakness and muscle atrophy
2. Pseudohypertrophy of the calf muscles
3. Wheelchair-bound by age 11
4. Death by age 25 due to respiratory and cardiac failure

C. Genetics:
1. incidence: 1/3500 males
2. Dystrophin gene mutations
a. Deletions most common
b. 1/3 are new mutations (Exception: remember autosomal dominant disorders, normally have new mutations). 2/3 of the time it is transmitted from the mother. (NO MALE TO MALE TRANSMISSION).
3. Carrier females may be mildly affected most likely with cardiac symptoms (ex: cardiomyopathy, mitral valve prolapse)
XXVIII. Glucose-6-Phosphate Dehydrogenase Deficiency
X linked recessive

B. Features:
1. Hemolytic anemia occurs in response to certain drugs, infections, foods (especially fava beans).
2. Anemia is self-limited
3. 10% of U. S. black males are affected (very common)

C. Pathologic Feature: Heinz bodies in RBCs and bitocytes– the spleen removes the Heinz bodies and makes it seem as if the RBCs have been bitten into.

D. Genetics: G6P dehydrogenase gene
XXIX. Hemophilia:
X linked recessive

B. Feature:
1. Easy bruising, hemorrhage, hemarthroses (bleeding into the joint)
2. Subtype A worse than B

C. Genetics:
1. Type A: factor VIII gene (Antihemophilic factor) (NT Note: A and Ate (8) – if that helps at all)
2. Type B: factor IX gene (Christmas factor)
3. 1/3 are new mutations; 2/3 are due from transmission from the mother
4. Carrier females are at risk for mild bleeding tendencies. Female teenagers tend to present with very heavy periods.