how many autosomes do we have
22
are single gene disorders transmitted the same between offspring?
yes
If a gene disorder is autosomal recessive, how many copies do you need in order for the trait to be expressed? what about autosomal dominate
recessive- would need two copies
dominate - only need one copy of the gene
is the transmission of an X-linked disorder the same between males and females?
no- FM have two copies of the X chromosome and one is generally a good one, however they can be carriers of the gene. In males the disorder is expressed because they only receive one copy of an X
common single gene disorders that are autosomal recessive
Cystic fibrosis
sickle cell anemia
phenylketonuria
Sickle cell anemia carriers show what
partly normal and partly sickled hemoglobin, which can usually keep them out of trouble, however if all their RBC are sickled this is problematic
what is phenylketonuria
we screen newborns for this, it is when individuals cannot metabolize the AA phenylalanine. Eating this AA can cause mental retardation, however if the individual avoids foods with this AA in them live a relatively normal life with no side effects
common single gene disorders that are autosomal dominate
marfan syndrome
huntington chorea
what is marfans syndrom
autosomal dominate disorder in which there is a connective tissue abnormality. affected individuals tend to be tall and skinny which causes skeletal problems, as well as possible aortic aneurism problems from cardiovascular problems
most common x-liked single gene disorder
hemophilia A- in males
what is huntingtons chorea
genetic disease that causes severe dementia, it can be seen in generations of families that are affected by it. symptoms don't appear until later in life (40-50), causes uncontrolled movements of the limbs
defects in chromosome number
easy for us to find through karyotyping, (turners, downs, kleinfelters)
monosomy
a defect in chromosomal number- having only one member of a homologous chromosome pair -only one X= turners syndrome
polysomy
having grater than usual number of autosomal chromosomes - trisomy 21 (downs), and trisomu XXy (klinefelters)
what happens when there is a defect in the chromosome structure
these are harder to find, it is when part of the chromosome is either added, deleted or duplicated in the wrong area.
what is translocation
where a chunk of one chromosome is take and then reattached to another chromosome in another location
what does nondisjuction mean
it is the failure of the chromosome to separate normally during meiosis or mitosis resulting in unequal distribution of chromosomes in daughter cells
what are the three common survivable nondisjunction chromosomal abnormalities
trisomy 21, tirsomy XXY, and monosomy X
what does aneuploidy mean
abnormal number of chromosomes- either to few or to many
what is trisomy XXY -klinefelters syndrome
extra X -chromosome, phenotypical male, extra x causes metabolic and other hormonal abnormalities
two types of genetic mutations
point mutation - involves single base pair substitution
frameshift mutation- dramatic change in genetic code
two types of chromosomal abnormalities
abnormal number of chromosomes and alterations in the structure of one more of the chromosomes
possible origins for abnormalities in chromosomes numbers?
radiation, viruses, and chemicals- because they interfere with mitosis and meiosis (in animals)
two conditions that increase risk of abnormal chromosome number in humans are
advanced maternal age, and abnormalities in parental chromosome structure
what is trisomy 21
chromosomal disorder in which individuals have an extra 21st chromosome. most common chromosomal disorder, causes mental retardation, protruding tongue, low set ears, poor muscle tone and short stature.
what is monosomy X
turners syndrome- ovaries fail to develop so affect individual is sterile, damaged X is of paternal origin and may be related to advanced age of the father. characteristics include, short stature, webbing of the neck, fibrous ovaries, sterility, amenorrhe
what is hemophilia A
bleeding disorder associated with a deficiency of factor VIII a protein necessary for blood clotting. individuals with this disease bleed profusely from minor injuries
mitochondrial gene mutations come from where
they come from the maternal egg, mothers transmit mitochondrial DNA to both sons and daughters. Mito DNA codes for enzymes involved in metabolism and mutations lead to dysfunctions in tissues with high ATP use
what are polygenic or multifactorial disorders
traits or disorders that do not follw clear cut modes of inheritance but do tend to run in families. characterisitcs that are governed by expression of several genes (height, weight, intelligence)
what is a teratogen
adverse influences during intrauterine life that can cause malformations of the fetus- can be due to radiation, chemicals and viral infections
when are teratogens most vulnerable in the life of a baby
between weeks 3 and 9- peak is at week 4-5 (organ developlement is happening at this time)
What is TORCH
was developed for clinicians to look for potential teratogenicty Toxoplamosis, Other, Rubella, Cytomegalovirus, Herpes
stages of hematology hemostasis
primary hemostasis
Secondary hemostasis
(clot retraction)
Primary hemostasis
immediate vasocontriction, slows blood flow to the area if from trauma. platelets stick to the wall and a clot begins to form, platelets not only adhear to endothelial layer and clump together to form a clot usually within 3-7 minutes
secondary hemostasis
involves formation of fibrin clot (coagulation) at the site of the injury. clotting factors are activated via the intrinsic or extrinsic pathway.
what is fibrinolysis
goes on at the same time the clot is forming - the process of fibrinolysis or clot dissolution is initiated. this is done by plasminogen being cleaved into plasmin, where plasmin digests fibrinogen and fibrin and inactivates the fibrin clot.
platelets
AKA thrombocytes, smallest formed element in the blood. they are produced in the BM from megakaryocytes. 70% of population is in the blood the other 30 is in the spleen. life span is 10 days
what increases platelet production
stress, epinephrine, and exercise, some growth factors
What do antiplatelet drugs do
are given to people who have a clotting risk factor, however when they are on the drug they have a higher bleeding risk(NSAIDS, asprin)
what is a common skin indication of low platelets counts
petchiae
what are the two common platelet disorders
thrombocytopenia-low platelet count
platelet dysfunction- where they dont stick together anymore
clotting factor disorder pathways
intrinsic-aPPT (partial thromboplastin time) measured in seconds
extrinsic-PT (prothombin time) and INR (internation normalizes ratio)
thrombocytopenia can be caused by what
decreased production, spleen sequestration, decreased platelet survival, intravascular dilution of platelets
possible causes for decreased platelet production
BM suppression by chemo, alcohol (disrupts RBC and platelets),, drugs, bone cancers aplastic anemia
possible causes for decreased lifespan for platelets
could be damaged or removed prematurely due to drugs, infections (viral), idopathic thrombocytoic purpora
possible causes for splenic sequestration of platelets
spleen becomes over aggressive and removes more than is should, may have to suppress spleen or remove spleen
what is thrombocytosis
platelet count above 400,000 mm usually follows stress or exercise
what does the PT/INR look at
assesses the extrinsic pathway of coagulation cascade and efficacy of Coumadin
what is von Wilebran disease
inherited autosomal dominate disorder of platelet dysfunction. von Wilbran factor is need for platelet adhesion to the epithelial wall, in people who have the disease they lack this factor. have high risk for bleeding out
vitamin K deficiency
fat soluble vitamin need for the coagulation cascade.
what is DIC
Disseminated intravascular coagulation- when both clotting and bleeding occur at the same time, chronic form mainly seen in patients with cancer. usually occurs because of a triggering event. (sepsis, cancer, post delivery for women)
what is erythropoisis
production of RBC
what are RBC responsible for
transporting O2 to the tissues of the body, and participating in removal of CO2 from the tissues as well as buffering the pH of the blood
what is hemotopoiesis
developmental process leading from pluralpoint stem cells into neutrophils, eosinophils, monocytes and platelets
requirments for erythropoisis are
dietary iron, folate, vitamin B12
what is the lifespan of an RBC
120 days
name the hormone produced by the kidneys which stimulates RBC production
erythropoietin
what is a reticulocyte
immature RBC that still has remnants of internal organelles, 1% of all RBC should be reticuloctyes
deficiency in iron
iron is not very absorb-able, due toGI bleeding (in men), mensuration in women
what is folate needed for
DNA synthesis, our body can make new DNA cells if there is a defiency however they come out larger than normal
what is vitamin B12 needed for
cofactor for DNA synthesis, need intrinsic factor in order to absorb B12
what is intrinsic factor
needed for the absorption of vitamin B12, made in the stomach by the parietal cells, pernicious anemia is an intrinsic factor deficiency.
what is MVC
mean corpuscular volume- size of RBC (mico/macro/normalcytic)
what is an RDW
range of red cell sizes, larger the range, the more variability in the size of the RBC
MCHC
mean corpuscualr hgb concentration- color of RBC
hypochromic- low heme=pale colored
smear
will tell you whether the RBC is sickled or abnormally shaped
what is a hemocrit
lab test done that looks at RBC count, looks at % total of RBC in the blood, usually 3x what your hemoglobin count is
what is polycythemia
increased RBC count
amenia is
decreased RBC count
what are the two categories of erythrocyte disorders
anemia
polycythemia
what are the two etiologies of polycythemia
primary- (polycythemia vera)- malignancy proliferation (cancer)- BM is overproducing RBC and there is no feedback inhibition to stop production
secondary- d/t compensation of hypotoximia or increased altitude
what is relative anemia
normal totoal red cell mass with disturbances in the regualtion of plasma volume-prego women
what is absolute anemia
types of anemia with an actual decrease in numbers of RBC, can be caused by decreased production of increased destruction
two types of anemais
increased loss due to bleeding
degradation to quickly before life span of RBC is over
clinical manifestations of anemia
fatigue, decreased activity tolerance, exertional dyspenea, increase respiratory rate, increased heart rate, hypotension, pallor
aplastic anemia
stem cell disorder that is characterized by a reduction of BM. this is usually caused by chemo/radiation therapy. also can be caused by epstein barr virus as well as HIV
types of anemia that are due to impaired RBC production
aplastic, iron, vitamin B12/folate(pernicious)
if the RBC is microcytic...
could be iron deficiency anemia, heomoglobinopathy (hemoe structure is abnormal) possible lead poisoning
if the MCV is normalcytic...
aplastic anemia, hemolytic- RBC lysis=increased bilirubin =jaundice in the skin, low erythropoetin, possible malignancy
if the MCV is macrocytic
low vit B12/folate- needed for DNA synthesis
how is anemia treated for decreased production of RBC
nutritional replacement of B12/folate, treat aplastic anemia if possible
how is increased loss anemia treated
stop bleeding, add iron
what is erythropoetin therapy
growth factor peptide that must be given parenerally, usually 1-3 times per week, should also give iron supplements to increase hematopoiesis
what does neoplasia mean
new growth- usually means abnormal cell growth for tumors
general characteristics of benign tumors
better tolerated by the body- stay localized
slower growing
often encapsulated by an epithelial layer
histological well differentiated
cells still do what they are suppose to do
rarely reoccur if removed
general characteristics of malignant tumors
rapid growth
metastasis occurs
invasive growth
anaplastic- disordered growth- further away from normal cell use
tissue/cell is dysfunctional
commonly recur if removed
oma means what
indicates benign tumor (expections are neuroblastoma and lymphoma=are both MALIGNANT)
what does carcinoma and sarcoma indicate
malignant tumor
90 % of malignant tumors are from what types of cells
epithelial cells
what are the number cells assocaited with the subclinical stage and lethal stage of cancer
subclinical- less than 1 billion/1gm
lethal- 1 trillion cells or 1/kg
carcinogens can be placed into two groups what are they
those that cause genetic damage (initiators) and those that promote growth of the tumor (promoters)
risk factors for cancer
tobacco use, obestiy, diet, UV light,
occupational exposure to benezene, herbicide, paint, asbestos
excessive radiation
HPV, EBV
family genes
GLUCOSE
grading of malignant tumors
histologic analysis of degree of anaplasia- look to see how malignant they are
staging of malignant tumors
description of location and pattern of spread- where the cells are in the body (local/spread out/regional/metastatic) use TNM
when staging a tumor T=
tumor is it local or invasive (1-4, and x=no tumor)
1 is small and localized
when staging a tumor N=
nodes=(no, yes, distant 0-3) has it spread. look at the sentinel node (first node in the drainage patter for where the tumor is, if it is clean then it is unlikely that the tumor has spead)
when staging a tumor M=
metastatic- yes/no M0,M1- tumor has left the local lymph nodes and metastasized somewhere else(nodes, organs tissues) M0- no detectable metastasis, just because they have not found any metastasis doesn't mean there isn't any, has to be large enough tumor
general stages of cancer
stage 0- carcinoma in situ, strictly local not invading,
stage I, II, III- higher numbers indicate more extensive disease: larger tumor size and or spread of the cancer beyond where it started. more disseminated (not metastatic)
Stage IV- cancer has sprea
steps in carcinogenesis
initiation phase-DNA mutation that activates proto-onco genes and inactivate tumor suppressor genes
promotion-mutant cell proliferation
progression- stage as which proliferation in cells beings to exhibit malignant behavior.
two important classes of genes involved with cancers caused by mutations are
normal proto-onco genes that are over active and tumor suppression genes that are inactive
two important tumor suppressor genes
pRb and p53
what does pRb do
pRb- master brake of the cell cycle, it inhibits transctiption
what does p53 do
p53-triggers apoptosis when it finds DNA damage, if cancer cells knock out this gene they can proliferate with out being killed
what is metastasis
process of spreading to sites distant from the primary site, enzymes and receptors help to facilitate this, usually the spread is predictable (follows lymphatic or blood stream)
what are tumor markers
way to TRY and find evidence of tumors in the blood, however it has not been very sucessful
effects of cancer on the host
asymptomatic until the later stages
pain
cachexia- wasting due to the fact that cancer is stealing nutrients
immunosuppression
infection
organ dysfunction
death
what is leukemia
WBC that are malignant and are in the blood stream, there are no early stages. it is disseminated from the beginning. leukemia starts in the BM
leukemia and lymphoma
are the same disease just at different stages, lymphoma is localized and leukemia's are disseminated. however the cells are the same that cause the disease
lymphoid leukemia is
involves T, B and NK cells
ALL-acute
CLL- chronic
malignant transformation of lymphocyte stem cell
myeloid leukemia is
involves granulocytes(neutophils....)
AML- Acute
CML- Chronic
lymphoid blasts
bad if in the blood, very abnormal and cause cancer
does radiation and chemo kill the cancer
NO....it just triggers apoptosis for any rapidly dividing cell, so slow growing tumors/cancers will not be affected
what is valance translocation
breakage in two chromosomes that reattach to each other in CML lymphomas, this forms a new chromosome which forms a protein, that protein causes the cell cycle to stay on.
two categories of lymphomas
Hodgkin lymphoma
non-Hodgkin lymphoma
characteristics of Hodgkin lymphoma
occurs in young adults, spread predictably, good prognosis in early stages, do lymph node biopsy
characteristics of non-Hodgkin lymphoma
(occurs in B, T, NK cells) happens in adults, spreading is unpredictable, poorer prognosis
manifestations of lymphomas
painless lymph node enlargement-lymphadenopathy
constitutional symptoms- non specific- low grade immue reaction for weeks
weight loss
night sweats
intermittent fevers
what is plasma cell myeloma
B-cells (NOT MYLOID)- when the plasma cells invade the BM and set up tumors there. can see monoclonal antibody production in serum levels (gamma region)
manifestation of plasma cell myeloma
bone pain, and pathological fractures, walking and hip broke the we find that the bone is riddled with tumors
high calcium in serum because of bone destruction
basic cancer therapy
de-bulk tumors to make them grow fast- them kill with chemo/radiation
antineopastic drug therapy- chemo
radiation
bone marrow/stem cell transplant
gene therapy
chemotherapy is cytotoxic to all rapidly dividing cells
true
as a primary treatment chemo is best for
cancers of the blood or lymph and small solid tumors
effects of chemo on the body
myelosuppression- leukopenia,anemia, thrombocytopenia
GI effects- inflammation of the tongue
alopecia
altered sexual/reproductive functioning
organ problems