Patho Exam 2

sickle cell anemia

single gene mutation with autosomal recessive inheritance

sickle cell mutation homozygous vs heterozygous mutation manifestations

homozygous: disease phenotype

Heterozygous: carrier

Point mutation leading to altered structure of the beta chain of hemoglobin in red blood cells producing

sickle shaped hemoglobin S (HbS)

six clinical manifestations of sickle cell anemia

* jaundice, anemia, pain, organ damage, infection (related to the proportion of HbS in the circulation)
* vaso-occlusive crisis
* infection and stroke in children

how long is the life cycle of a red blood cell

120 days

lab analysis for sickle cell anemia (4 methods)

* determine proportion of hemoglobin types
* complete blood count
* urinalysis
* tests of liver and kidney function

what are symptom specific treatments for sickle cell

* avoidance of temperature extremes
* reduction in emotional and physical stress

drugs that can be used for sickle cell

* promote production of RBCs with hemoglobin F
* treatment of pain and infection

what is the mutation that occurs in sickle cell

where there should be a T there was a C changing the sequence to glycine making hemoglobin nonfunctional (recessive gene)

what type of dominance can sickle cell have

codominance (both alleles are fully expressed in the heterozygous state)

how long can an SS blood cell live

20 days (blood cells dying frequently causes jaundice)

what is vaso-occlusive crisis

sickle cell blood cells stick together and block blood flow in blood vessels

what are three characteristics of a vast occlusive crisis

* gets worse in cold temp because of more constriction and more occlusion
* pain d/t ischemia (organ damage)
* spleen can die (more susceptible to infection)

sickle cell in a heterzygous state

some normal cells and some with sickle cell hemoglobin. Infection and stroke are common for children with SCA

what is jaundice

excess of bile pigments

Baby has different hemoglobin which turns off when the baby is born and the normal hemoglobin gene turns on

this is the one that can mutate resulting in a SC hemoglobin gene

Hydroxyurea and sickle cell anemia

turns on fetal hemoglobin gene in those with sickle cell

what is MELAS

Mitochondrial Encephalomyopathy, Lactic, Acidosis, Stroke

what cases MELAS and what type of inheritance is it

mitochondrial gene mutation in the mtDNA (matrilineal inheritance)

Errors in the transcription of the genetic code lead to impaired

energy production and use

what are two enzymes that are affected by MELAS

cytochrome oxidase (COX) and succinate dehydrogenase (SDH)

what are four variable manifestations of MELAS

encephalopathy, lactic acidosis, stroke like episodes, cardiomyopathy

clinical manifestations are based on what

mutant mtDNA levels

what is hemiparesis in MELAS

stroke-like episodes with temporary muscle weakness on one side of the body

what is hemiplegia MELAS

paralysis on one side of the body

what are the four diagnostic criteria for MELAS

* history and physical exam
* lab studies
* muscle biopsy
* imaging studies

lab studies for MELAS (3)

* mitochondrial respiration
* lactic acid and pyretic acid
* mtDNA mutations

what does the muscle biopsy reveal

ragged red fibers

in MELAS pyruvic acid only becomes

lactic acid

what is the pathway from pyruvate that prevents lactic acidosis

pyruvate to acetyl CoA

what does pharmacologic treatment do for MELAS patients

reduces seizures and promotes mitochondrial energy production

what cells in the body need the most energy

neurons and muscle cells

what causes down syndrome

alteration in autosome number

there is trisome (three copies) of which chromosome

21

trisomy 21 is a result of

nondisjuncture or inherited translocation

what type of DS occurs after fertilization

mosaic Down syndrome

what are eight clinical manifestations of Down syndrome

* mental delay
* altered facial features
* cardiac defects
* gastrointestinal malformations
* visual and hearing impairment
* thyroid disfunction
* leukemia
* decreased muscle tone

how is DS diagnosed in the first trimester

* nuchal translucency (measures nuchal fold thickness, back of neck)
* PAPP-A TEST (pregnancy associated plasma protein - A)
* anatomic anomalies (high calcification in heart, bowel)

how is DS diagnosed in the second trimester

* quadruple test - HCG, estradiol, inhibin, AFP
* integrated test - nuchal, PAPP-A, and quadruple
* anatomic anomalies (high calcification in heart, bowel)
* fetal karyotype

what are treatments and interventions done for those with DS

* promotion of maximal independence and quality of life
* early intervention of therapies
* physical
* speech
* occupational

what causes Turner syndrome

monosomy of chromosome X

turner syndrom results in a decreased life expectancy as well as

diabetes and heart disease

clinical manifestations of turner syndrome

* short
* gonadal failure: delayed puberty, infertility, and premature menopause
* cardiac and kidney abnormalities
* skeletal and soft tissue abnormalities
* hearing loss
* learning difficulties and social problems

how is turner syndrome diagnosed

* history and physical exam
* prenatal screening tests
* karyotype and genetic testing

prenatal screening tests

* hygroma on back of neck
* edema
* short femur
* narrow aortic arch

what are treatments for turner syndrome

* symptom specific
* assistance in socialization
* hormonal therapy

people with mosaic turner syndrome have some chance of

getting pregnant

people with turner syndrome have decreased

life expectancies

what is a sex-linked genetic disorder following mendelian inheritance patterns (defect on chromosome X impairs production of the fragile X mental retardation protein) (FMRP)

fragile X syndrome

fragile X is the leading cause of

inheritable mental retardation

fragile X primarily affects who and who are normally carriers

primarily affects males and females are often carriers

what are four clinical manifestations of fragile X

* distinctive facial features
* connective tissue abnormalities
* macroorchidism (enlarged testicles)
* cognitive impairment and behavioral difficulties

three diagnostic criteria for fragile X

* history and physical examination
* genetic screening
* prenatal screening

what are two treatments for fragile x

* behavioral and educational management
* pharmacologic: drugs to manage mental status and behavior

a premutation for fragile X has how many CGG repeats

55-200

CGG a full mutation in fragile X has how many

200

what are three clinical manifestations of fragile X

elongated face, protruding ears, poor muscle tone

why is it called fragile X

when trying a karyotype with a person with this genome the chromosome breaks

what does a parent of a child with fragile X have

has a premutation, goes through generation and eventually reaches full mutation status

what is the etiology of someone with fragile X

no functional FMRP (premutation is normal but their children could be full mutation)

how will the genotypes of the children be affected if their father has fragile X

it will not transfer to sons and all daughters will be carriers (assuming the mother is normal

huntington’s

Progressive degenerative neurologic disorder with an autosomal dominant inheritance pattern (defect in hungtington gene on chromosome 4)

where is the degeneration for a person with hunutington’s

basal ganglia and cortical regions of the brain (movement, emotional, and cognitive impairment)

clinical manifestations

* involuntary movements
* cognitive impairment
* emotional disturbance

how is huntington’s diagnosed

* history and physical
* mental, cognitive and emotional evaluation
* genetic testing

If basal ganglia doesn’t stop muscles when they’re not in use they will keep moving and this is known as

huntington’s chorea (choriform movements)

what is destroyed in huntington’s disease

basal ganglia

what is the difference in age onset of symptoms when it is inherited from the father vs. the mother

If this gene is inherited from the father you will get it in adolescents, from the mother it come at middle age due to imprinting

what is the leading cause of cancer deaths worldwide

lung cancer

where do lung cancer tumors originate frequently

epithelial lining of the bronchi,bronchioles, and alveoli

what ater four subtypes of lung cancer and how common are they

* adenocarcinoma (35%)
* squamous cell carcinoma (30%)
* large cell carcinoma (15%)
* small cell carcinoma (205)

four clinical manifestations for lung cancer

* persistent cough
* hemoptysis (blood in sputum)
* chest pain
* shortness of breath

what are five ways lung cancer is diagnosed

* bronchoscopy
* chest radiography
* tissue biopsy or cytology
* MRI, CT, ultrasound
* carcinoembryonic antigen (CEA)

how is lung cancer treated

based on tumor type

how is small cell carcinoma treated

chemotherapy

how is non-small cell carcinoma treated

* surgery
* chemotherapy
* radiation if surgery not feasible

stage 1 lung cancer

located on in lungs, not in lymph nodes

stage 2 lung cancer

in lungs and nearby lymphnodes

stage 3 lung cancer

in the lung and lymphnodes in the middle of the chest, locally advanced

stage 4 lung cancer

advanced disease - both lungs, fluid in area around lungs, and another part of the body such as liver or other organs

there are multiple lifestyle risks for

colorectal cancer

disruption of what gene is seen in three of four cases of colorectal cancer

p53

in colorectal cancer there is cellular transformation in mucosal epithelium of the bowel beginning at the

base of the crypt

five clinical manifestations of colorectal cancer

* Change in bowel habits
* Occult (hidden) or frank ( visible) blood in stool
* Abdominal pain
* Bowel obstruction
* Anemia

how is colorectal cancer diagnosed

* digital rectal exam
* colonoscopy
* CEA

how is colorectal cancer treated

* surgery
* chemotherapy
* radiation

what is TNM classification

T - primary tumor

N - regional lymph nodes

M - distant metastasis

if there is no metastasis what treatment can be used?

surgery

what is HNPCC

hereditary nonpolyposis colorectal cancer (accounts for 1 in 6 colon cancer cases)

metastasis is much more common to brain than primary tumors

10:1 ratio

where are five places that primary tumors originate

* glial cells
* schwann cells
* meninges
* oligodendrocytes
* ectopic tissues

what are five clinical manifestations of brain cancer

* headache
* vomiting
* seisures
* loss of motor or sensory function
* cognitive or behavioral changes

low grade astrocytoma account for what percent of primary tumors in 30s and 40s

15%

what is the median survival rate for low grade (II) astrocytoma

5-8 years

what grade is glioblastoma multiform (GBM)

IV

what type of astrocytoma is GBM

malignant

GBM represents what percent of primary tumors in ages 55-75 and how long is the average survival rate

25%, 14-18 months

what accounts for 15-20% of primary tumors and occurs in 2 peaks 35 and 55

oligodendroglioma

how does the survival rate for oligodendroglioma compare to that of astrocytoma

slightly better

ependymoma

lines spinal fluid cavities in brain and spinal cord