MT2 Flashcards
How many protein-coding genes in Human Genome Project
19,000
Mutations affecting ___ cells can be inherited (basis of genetic disease)
Mutations affecting ____ cells can result in tumors (usually not inherited/passed along)
Germ
Somatic
Which type of mutation alters reading of RNA
Frameshift mutations
Fragile X syndrome is what type of mutation?
Trinucleotide repeat mutation
Where are polymorphisms usually found?
What are their significance for disease?
NON coding regions (i.e. introns & exons)
They are markers
Copy number variation is an example of a ____, therefore, it’s recognized as a ____
polymorphism
marker
Epigentic change is a ___ that reduces/shuts down ____ by:
polymorphism
translocation (protein synth)
methylation of cytosine residues
Which polymorphism controls gene silencing?
Micro-RNA’s
Autosomal ___ disorder will be evident clinically when only one of the chromosomes in the pair (heterozygous) exhibits a mutation
dominant
Majority of automsomal ____ create outward physical changes.
Early/late age of onset?
Example:
dominant
LATE (even though mutant gene is present from birth)
Huntington’s Disease
If one of the parents is infected and half the offspring are affected, it’s autosomal ____
dominant
Which disease has nearly 100% penetrance
neurofibramotosis
What is variable expressivity?
Trait is seen phenotypically, but is expressed differently among individuals
De novo mutation:
If a kid has an autosomal disorder and neither of the parents have it
Which is a largest group of mendelian disorders?
Autosomal recessive
For autosomal recessive, do the parents usually show the disease?
NO
Autosomal ___ is when you need a germline from both parents to develop disease
recessive
Autosomal recessive commonly effects enzyme for:
metabolism
For autosomal recessive, the age is onset is ___ in life
The expression tends to be ___ uniform and ___ penetrance is common
earlier
more uniform
complete penetrance
X-linked disorders are almost always (dom/rec)
If a man inherits an x-linked recessive (almost all are recessive), is he always affected?
Recessive
YES
When lyonization occurs, what is left in the female zygote?
What is unfavorable lyonization causes clinical evidence of an _____ disease in a ___zygote.
- Example:
Barr body
x-linked disease in a heterozygote.
Ex. hemophilia A
A patient has coarse facial features, clouding of cornea, joint stiffness, and mental retardation. They have _____ which is due to lack of _____. It’s a _______disease
- Mucopolysaccharidoses
- Lack of enzyme to degrade mucopolysachharides
- Lysosomal Storage Disease
What are some things that come from MULTIFACTORIAL inheritance?
Frequency of inheritance:
- Physiologic traits (i.e. height, weight, hair color, BP, etc)
- Common diseases (i.e. diabetes, hypertension, gout, schizo)
-2-7%
Prevalence of newborns that have a chromosomal abnormality:
In as many as __% of 1st trimester spontaneous abortions, the fetus has a chromosomal abnormality
1/200
50%
Euploid: Polyploidy: Aneuploidy: Trisomy: Monosomy:
- Euploid: normal
- Polyploidy: multiple of 23 (SPONTANEOUS ABORTION)
- Aneuploidy: any number that is not exact multiple of 23 (ASSOCIATED W MANY NEOPLASIAS -CANCER)
- Trisomy: 1 extra chromosome
- Monosomy: 1 less chromosome
Translocation:
Reciprocal translocation:
Deletion:
Inversion:
- Translocation: transfer of a part of 1 chromosome to another nonhomologous chromosome
- Reciprocal translocation: fragments are exchanged between 2 chromosomes
- Deletion: loss of a portion of a chromosome
- Inversion: chromosome breaks in 2 points, then the released fragment turns around and then reunites
Indications for genetic analysis..
Prenatal:
Postnatal:
PREnatal: -Mother >34yrs old -Parent is carrier of chromosomal translocation/ or x-linked disorder POSTnatal: -Multiple congenital anomalies -Mental retardation -Infertility
What does arteriosclerosis due to arteries
harderns arteries
Which type of arteriosclerosis is calcification WITHOUT luminal narrowing or disruption (so blood flow is ok)
Monckeberg’s
Difference of hyaline and hyperplastic arteriosclerosis..
- which causes narrowing of lumen?
- which causes thickening of basement membrane?
- which causes fibrocellular intimal thickening
- which is more affected by diabetes?
- hyperplastic = narrowing of lumen
- hyaline = thickening of basement membrane
- hyperplastic = fibrocellular intimal thickening
- hyaline more affected by diabetes
What disease is responsible for more death than any other?
Vascular disease
Arterial vs. Venous side... Which is high pressure? Which has strong muscular wall? Which has a more elastic wall? Which has a larger lumen?
Arterial = high pressure Arterial = strong muscular (to withstand pressure) Venous = elastic wall Venous = larger lumen (dilates easily)
Death rate for all atherosclerosis?
__% due to MI
50%
25% due to MI
What is the most important NON-modifiable risk factor for arteriosclerosis?
Genetics (family history of MI)
What modifiable risk factor for arteriosclerosis increases death rate by 200%?
What is a risk factor in the oral cavity?
smoking
inflammation (CRP- inflammatory marker)
Atherosclerosis: response to injury hypothesis…
- Endothelial injury results in endothelial dysfunction
- Accumulation of lipoproteins
- Monocyte adhesion =
Monocyte adhesion = migration into intima w/ differentiation into macrophages and “foam cells” (macrophages that have ingested lipid)
Atherosclerotic plaque (an atheroma) has a ____ cap, a _____ core and has progressive changes (which includes _____)
fibrous cap
central lipid core
fissure formation
Fatty streaks occur in what age?
They can be in atherosclerotic and nonatherosclertoic prone geographic areas and are characterized by:
Infants and children
Lipid-laden cells in the intima
A complication of ATHEROSCLEROSIS that’s due to pressure atrophy of the media w/ altered balance of collagen synthesis/degradation is?
-It leads to?
-Other complications?
Aneurysm
Sudden death
-gangrene, renal artery stenosis (atrophy of kidney)…
Hypertension prevalence
Normal?
Severe?
25%
Normal 160/106
Which type of hypertension accounts for 90%?
What are some contributing factors of essential hypertension?
What symptoms do most patients have?
Essential hypertension
Genetics, stress, obesity, increased salt intake, smoking
NONE until organ damage has already occured!
With Essential Hypertension, what happens during compensation?
What happens if you add dilation?
Concentric left ventricular hypertrophy…the muscles get stronger and makes the ventricular chamber smaller (cardiac output at risk)…makes heart pump faster
Dilation causes it to be DEcompensated. Big heart but can’t pump very well. Leads to CHF
Hypertension causes ____ sodium excretion –> salt and water ___ –> ____plasma volume and cardiac output
reduced excretion
salt and water retention
increases plasma volume and cardiac output
What is Congestive Heart Failure?
Affects how many people in US annually?
Contributes to ____deaths
Failure of the heart to pump an adequate amount of blood to supply the metabolic requirements
5 million
300,000
CHF compensatory mechanism..
Initially:
Then:
Activation of neurohumoral system releases ____ w/ increased __ + ___. Activation of ____ system w/ water/salt retention –> increased circulatory volume
Initially: Myocardial hypertrophy (helps initially, but the larger muscle fibers require more oxygen from the capillaries, which is not typically available)
Then: Frank-Starling mechanism (ventricular dilation)…as you stretch cardiac muscle, it’ll push out more forcefully
release of NE w/ increased HR + contractility
-Activation of renin-angiotensin system
Biggest cause of LEFT-side heart failure?
Biggest cause of RIGHT side failure?
Other causes of right side:
Ischemic heart disease
Left side heart failure
-pulmonary (lung) hypertension (cor pulmonate), valve disease, septal defects w/ left to right shunts
Most common manifestation of CHF:
CHF due to __ side leads to __ failure
Left ventricular failure causes ___ edema
Right ventricular failure (caused by left failure causing congestion) causes congestion of ____ AND edema of ____
Left ventricular failure
Left failure leads to right failure (cuz left doesn’t pump out enough so it congests the right)
Pulmonary edema (difficulty breathing while lying down)
Congestion of liver and spleen AND edema of feet and ankle
Prevalence of Congenital heart disease:
What are the two forms:
6/1,000 births
Cyanotic (right –> left) (shunting of poorly-oxygenated venous return to systemic arterial circulation.)
Noncyanotic (left–>right)
What are the 2 cyanotic congenital heart diseases?
This can cause what clinically:
Most common congenital heart disease:
Tetrology of Fallot + Transpostion
- clubbing of fingers
- Ventricular septal defect
Leading cause of death in the US?
Ischemic Heart Disease. 500,000 per year
During Ischemic heart disease, narrowing of ____ by at least __% by atherosclerosis.
Other factors:
narrowing of coronary arteries by at least 75%
Shock, pneumonia, anemia
3 types of cardiomyopathy:
Dilated
Hypertrophic
Restrictive
DILATED cardiomyopathy:
dilation of all 4 chambers
HYPERTROPHIC cardiomyopathy:
Genetic
ASYMMETRIC HYPERTROPHY
RESTRICTIVE cardiomyopathy:
decrease in ventricular compliance (wall is stiffer)
Acute vs Subacute Endocarditis... Which has large vegetations? Which is longer duration? Which has a more virulent organism? Which has a previously normal valve? Which has more tissue destruction
Large vegetations: Acute Longer = subacute More virulent = Acute Previously normal valve = acute More tissue destruction = acute
Vasculitis:
What causes vasculitis to be worse?
Inflammation of blood vessels
Immune complexes
What are the 2 ANCA - positive forms of vasculitis?
Wegener’s and microscopic polyarteritis
Leukemias are malignant proliferations of cells native to the _____ which often spillover into the ___. They can spread to involve ____
bone marrow
blood
organs (usually liver and spleen..but also gingiva)
Hodgkin VS NHL... Which has RS cells Usually has multiple node involvement: More common: Which is based on STAGE (location): Which is based on GRADING (morphology): Which affects ALL ages: Large painless lymph nodes:
RS = Hodgkin Multiple node = NHL More common = NHL Stage = Hodgkin Grading = NHL All ages = NHL Large painless nodes = BOTH
Biggest difference between acute and chronic Leukemias (with regards to bone marrow)
Acute has an increase in blasts (chronic doesn’t have an increase in blasts)
Acute Lympoblastic Leukemia (ALL) vs Acute Myeloblastic Leukemia (AML)
- Enlargement of lymph nodes, liver and spleen more common in:
- Often involves CNS:
- Which affects mostly children..which affects mostly adults
- Remission more common with
- Enlargement more common = ALL
- CNS = ALL
- Children = ALL
- Adults = AML
- Remission = AML
What are the 2 main clinical features of Leukemia?
1) impairment of marrow function
2 )infiltration of body organs
In plasma cell disorders, the secreted immunoglobulin results in increases of ________, which may have adverse effects on ___ and ___ fucntion
- increase of serum monoclonal protein (M component)
- Adverse effects on renal and neurologic function
Do testing for anemia DIRECTLY measure the red cell mass?
Whats an INCREASE in red cell mass called?
NO! just reflect
Polycythemia
RBC loss // Decreased RBC survival // or Decreased RBC production... ***Nutritional deficiency: Hemorrhage: Hemolysis (transplant not doing well): Malaria: Iron anemia: Hemolytic anemia:
Nutritional = decreased PRODUCTION Hemorrhage = loss Hemolysis (transplant) = decreased survival Malaria = decreased survival Iron anemia = decreased production Hemolytic anemia = decreased survival
Coomb’s test is an autoimmune test to see if there is:
immunoglobulin on blood cells
Young healthy subjects can tolerate rapid blood loss of ____ml (__% of total).
Interstitial fluid will redistribute within ___
Rapid blood loss of ____ml produces shock
500-1000ml (15-20%)
24 hrs
2000ml
The loss of RBC stimulates increased production, mediated by ____, resulting in an increase in the ____ count in the peripheral blood
mediated by erythropoietin
increase in the reticulocyte count
Chronic blood loss causes anemia when:
loss exceeds regeneration OR when iron reserves are depleted
Which are usually inherited? Which are normally acquired (intrinsic/extrinsic hemolytic anemia)
Intrinsic = inherited Extrinsic = acquired
What is the most common cause of anemia in the world?
RBCs appearance:
Important to recognize anemia may be a sign of a more serious disorder associated w/ chronic blood loss (ie _____)
iron deficiency
- pale and white
- cancer
Megaloblastic anemia is deficiency of:
They are both involved w/ synthesis of:
End result is abnormally ___RBC precursor, _____ production of MATURE RBCs, and abnormally large ____cells.
B12 and folate
- thymidine
- abnormally large RBC precursor (megaloblast),
- decreased production of MATURE RBCs
- also large white cells
Where is B12 found?
Body stores? (large or small)
Folate is found?
Body stores?
B12: animal foods
Stores: large
Folate: vegetables
Stores: small
Hemostasis definition:
3 major components of hemostasis
ability to maintain blood in a fluid state AND prevent loss from sites of damage (hence “stasis”… equilibrium)
-vascular wall, platelets, coagulation proteins
Primary hemostasis is ___driven
Secondary hemostasis is ___driven
Primary = platelet Secondary = coagulation (thrombin/fibrin)
During primary hemostasis, platelet adhesion involves activation of:
What’s the surface it adheres to?
What mediates the adherence of platelets?
- surface membrane receptor (glycoprotein Ib)
- subendothelial matrix (collagen)
- vWF mediates adherence
Activation of primary hemostasis….
Secretion:
Activation of:
Shape change:
Secretes: alpha granules
- activation of GP IIb/IIIa receptor
- from discoid to spherical
Aggregation of primary hemostasis…
dependent on:
Platelet-platelt binding mediated by:
calcium
-fibrinogen
What does thrombin do (secondary hemostasis).
What does it do to the clot?
Converts fibrinogen to fibrin
-Adds stability to the clot
Which pathway is more important in secondary hemostasis?
It’s activated by:
EXTRINSIC
-tissue factor
Antithrombins def:
inhibit activity of thrombin and other serine proteases
What is the protein C system?
What’s the major effector enzyme, what’s the major cofactor?
Deficiencies in this system would cause:
What does Factor V Ledin mutation promote?
REGULATES hemostasis (they slow down hemostasis) -Protein C is the major effector enzyme, protein s is a major cofactor
Hypercoagulability
-Coagulation
Summary of REGULATION of coagulation…
Antithrombin inhibits:
Protein c inhibits:
Plasmin breaks down:
Antithrombin inhbits serine proteases
Protein C inhibits cofactors
Plasmin breaks down fibrin clot
Screening tests to evaluate hemostasis…
Prothrombin Time def:
***Used to initiate ____ coagulation cascade
time needed for plasma to form a clot in the presence of added tissue thromboplastin
EXTRINSIC
Screening tests to evaluate hemostasis…
Partial Thromboplastin Time
Measurement of ____ pathway
time needed for plasma to form a clot in the presence of added ground glass or kaolin (to activate factor XII)
INTRINSIC
When either the PT or PTT is prolonged, a ______ with 1:1 ratio of normal plasma:patient plasma is performed.
If mixing study corrects clotting time, px has ____ of factors.
If the mixing times does NOT correct the clotting time, an ____is present (either ____ or _____type)
mixed study
deficiency of factors
inhibitor (factor-specific or lupus anticoagulant type)
If bleeding disorder screening laboratory tests are normal, disorder of the ____ system may be suspected
regulatory
Disorders of Primary or Secondary hemostasis
Which causes more superficial bleeding (i.e. mucosa)?
Which causes deeper bleeding (i.e. joints)?
Primary = superficial Secondary = deeper
vWF functions both as the carrier molecule for ______ and as the “glue” between damaged endothelium and platelets (primary hemostasis)
Factor VIII
How is Hemophilia B different than A?
How is vWF disease different than Hemo A
Decreased production of Factor IX (instead of VIII in A)
vWF has mucocutaneous bleeding
Autosomal dominant vs recessive polycystic kidney disease….
- In adults:
- Kids:
- Which is more common (1:500-1000):
- Gradual onset:
- ***Creates cysts in Circle of Willis (intracranial):
- Has the gene mutation that includes liver (pkHd1..H is hepatic):
- Causes very large kidneys:
- Cysts arise from collecting tubules
- Adults = dominant
- Kids = recessive
- More common = dominant
- Gradual = dominant (hence adults)
- **Intracranial cysts = dominant
- PKHD1 = recessive
- Large kidneys = dominant
- Collecting Tubules = recessive
What are the 2 mechanisms of Glomerular Injury:
- Immune complex deposits in Glomerular Basement Membrane (GBM)
- Epithelial and endothelial injury
For evaluation of kidney biopsies, you use EM (electron microscopy) to identify:
More specific location of beasement membrane
3 things that kidney disease will affect:
Glomeruli
Renal Veins
Renal Pelvis
Thrombotic Thrombocytopenia Purpura (TTP) AND Hemolytic-Uremic Syndrome (HUS) are related to activation, aggregation, and consumption of:
Which one affects kidney?
Which one affects more organs?
platalets
TTP= all organs (including CNS) HUS= just kidney
WHo is at high risk for kidney stones because of high cell turnover?
Ppl with Leukemia
Glycoprotein IIb/IIIa on the _____ binds ___
on the PLATELETS binds FIBRINOGEN
Heparin works the same way as ____. Which works by stopping:
antithrombin
stopping thrombin from making fibrin (inhibit serine proteases)
