Cells and Genetics Flashcards
Cellular injury
Result of a stimulus in excess of the cells adaptive response
Cellular adaptation
Compensation that occurs at the cellular level
Where will hyperplasia not take place?
Cells that can’t replicate (heart, neurons, muscle, etc)
Dysplasia
cells that are abnormal in size, shape, or organization. These are abnormal cells that are not necessarily cancer. Ex- wart
Cancers will be
dysplastic and neoplastic
Neoplasia
Abnormal, disorganized growth (a tumor). May or may not be cancer.
4 Themes of cellular injury
1) ATP depletion (often due to lack of O2)
2) Free radicals and reactive oxygen species (cause oxidation of membranes and other structures, often a problem with re-perfusion)
3) Increase in intracellular Ca++ (release of Ca from mitochondria, lack of ATP to remove it, activation of many enzymes from Ca, very high Ca levels signal apoptosis)
4) Defects in plasma membrane (loss of normal cell function, loss of Na+ gradient, activation of proteases and phospholpases)
Marker of cellular death
Creatine kinase
Result of intracellular decrease in pH
Nuclear chromatin clumping and swelling of lysosomes (this welling then causes a release of lysosomal enzymes that begin autodigestion)
2 key players in irreversible cell injury
Lack of ATP generation and major damage to membrane function
Most common cause of cellular injury
Hypoxia
Most common cause of hypoxia
Ischemia
Ischemia
Inefficient blood supply to tissue or ogan
Infarction
Ischemia with necrosis
How does a reperfusion injury occur?
Reperfusion with oxygen results in the production of xanthin oxidase, which goes on to make massive amounts of superoxide, H2O2, and nitric oxide (another free radical). Basically, the reperfusion results in formation of ROS that can cause necrosis.
Main oxidants in our bodies
Superoxide anion, hydrogen peroxide, and hydroxyl radical. We want to get rid of these ASAP!!
O2- is converted to _____ by ______
O2 and H2O2 Superoxide dismutase (SOD)
Hydroxyl radical is converted to ______ by _____
H2O2
Glutathione peroxidase
H2O2 is converted to _______ by _____
H2O
Catalase
Interestingly, animals with more catalase tend to live longer
How is O2 converted into O2- (superoxide)?
By oxidative enzymes in the mitochondria, ER, plasma membrane, peroxisomes, and cytosol.
Process of apoptosis
Initial changes include nuclear chromatin condensation and fragmentation, followed by cellular shrinking & budding, and phagocytosis of those apoptotic bodies. No cytoplasm is released during apoptosis and it does not result in an inflammatory response!
Process of coagulation necrosis
Chromatin clumping, organelle swelling, and eventual membrane damage. Cytoplasm will leak and release intracellular enzymes. Immune system is recruited.
Point to note between necrosis and apoptosis
Apoptosis involves cellular shrinking and then budding. Necrosis involves swelling and lysis.
4 Types of Necrosis
Coagulative
Liquefactive
Caseous
Fat
Coagulative necrosis
Usually due to ischemic infarction anywhere except the brain. In this type of necrosis, everything is dead, but the cytoskeleton and general cellular structure remain intact
Liquefactive Necrosis
This involves enzymatic digestion of cells to form a liquid, viscous mass. Usually due to a bacterial or fungal infection d/t it’s ability to stimulate an inflammatory response. After removal of cellular debris by WBCs, a liquid filled space is left. This type of necrosis occurs in the brain because it has many digestive enzymes and little connective tissue. The cell architecture is lost in this type of necrosis, which is why it is liquid. Pus is also liquefactive necrosis.
Caseous necrosis
Happens as a result of TB infections. Looks like a yellow-white, cheesy debris. This is kind of like a combo between coagulative and liquefactive necrosis.
Fat necrosis
In this necrosis, lipases act on fats. This results in the release of ffas from triglycerides. These ffas then complex with calcium to form soaps, which appear as white, chalky deposits. This is often associated with pancreatitis. This is also why those with pancreatitis have low Ca levels.
Dry gangrene
A form of coagulative necrosis and is due to ischemia (lack of arterial blood flow).
Wet gangrene
This is coagulative necrosis progressing to liquefactive necrosis, and usually happens in parts of the body that are naturally moist. This is often characterized by thriving bacteria and has poor prognosis due to septicemia. As opposed to dry gangrene, this is often due to blockage of venous flow (the affected part is saturated with stagnant blood)
These cells have active telomerase activity
Germ cells and stem cells. However, only germ cells have sufficient levels of telomerase to maintain telomere length indefinitely.
Number of replications we have per telomere
40-60
BUN and creatinine are monitors of kidney function, but they can be influenced by
BUN- also reflects diet and hydration
Creatinine- can go up and down with how much muscle mass you have
Anion gap
Tells you if your acidosis is a gain of acid or a loss of base
Why can’t you tell if you are calcium deficient or overloaded by looking at serum calcium levels?
Because we balance levels using bone calcium
Function of uric acid in the blood
Antioxidant
Alkaline phosphatase and Gamma-GT
Found in cells lining the bile ducts. Elevation will mean necrosis of these areas.
Alkaline phosphatase can also indicate bone problems such as bone cancer
Problem with high phos
Can bind with calcium and cause ectopic calcifications
Direct bilirubin
This is conjugated bilirubin (bilirubin that has been made water soluble by the liver)
Total bilirubin
Conj + Unconj bilirubin. Can help you determine if the problem is before, with, or after the liver.
Plasma albumin
Most common protein of the PLASMA (not of the blood). The liver will as much or as little albumin as it needs to make in order to get your plasma protein at the right level. Looked at in conjunction with total protein. If plasma protein is high, and albumin is low- this isn’t a problem with the liver, it means that someone else is making too much protein so the liver didn’t need to make much albumin. This could be caused by multiple myeloma (cancer of the plasma cells- causes antibody excess). If both levels are low, this could be a liver or kidney problem.
LDH
Enzyme that converts pyruvate to lactate. It is found in every cell that does glycolysis, which is every cell in your body! It is a marker of cell death. Physical assessment will tell you where you should be looking for the cell death. There are various isozymes of LDH that are more tissue specific. The same LDH isoyme found in RBCs is also found in cardiomyocytes. Remember that if there is bad phlebotomy with lysis of RBCs, the lab values could falsely indicate an MI. Look at potassium in this case, if the K+ is excessively high, it points towards bad phlebotomy.
We have this many times more RBCs than WBCs
1000x more
Ivy method of bleeding time
10mmx1mm cut
Duke method of bleeding time
Finger/earlobe stick
Reticulocytes
Can help you assess the cause of anemia. Is it bleeding problem, marrow problem, etc
Hematocrit should be about ___ times more than Hgb
- Tells you if the cells are larger or smaller than they should be
MCV
tells you the average size of an RBC in your body
Prothrombin Time
Measures clotting via the extrinsic pathway. We won’t see this as often as INR. This is dependent on Vitamin K. We measure this for those of warfarin (coumadin) therapy
INR
International normalized rate. Your clotting rate compared to the “average” person’s clotting rate. Less than one = faster clotting. Larger than 1 = slower clotting. 1 = normal.
APTT
Intrinsic clotting pathway
Insertions and deletions result in this type of mutation
Frame-shift mutation
SNP
Single nucleotide polymorphism. One base pair is substituted for another
Dominant X-linked disorders are almost always _____ for males
fatal in utero
Examples of x-linked recessive disorders
Hemophilia A (factor XIII), Hemophilia B (factor IX), duchenne muscular dystrophy
Locus
location in the genome
Penetrance
The chance that phenotype will follow the genotype
Haplotype
Alleles on a single chromosome
Cross-over/recombination
Gene rearrangement between homologous chromosomes
Translocation
Swapping of genetic material between nonhomologous chromosomes
Do we have more than two copies of any genes?
Yes. We have WAY more than 2 copies of the ATP pump for example
Chromatid
One copy of a duplicated chromosome
Each oocyte gives rise to
One egg and three polar bodies
Aneuploidy is caused by
Nondisjunction (failure of chromosome pairs to separate properly during meiosis I or II)
Manifestations of Turner’s Syndrome
Infertility, many cardiac problems, webbed neck, underdeveloped breasts and widely spaced nipples
Manifestations of Klinefelter’s
Small testes, infertile, some breast development, sparse body hair, and long limbs. Can be XXY or XXXY. You get about a 15 point reduction in IQ for each extra X.
Extra Y chromosome
Slightly bigger, dumber, and more aggressive.
When does crossover happen?
Prophase I
Cri du chat is caused by
a deletion of part of 5q
Error that can occur during crossover
Duplication/deletion
Effect of translocations
A child born with translocations will usually be totally fine because they have all the genetic material they need, it just might be in the wrong place. However, they may have issues with miscarriage later on in life due to risk of creating gametes with unbalances translocations
Examples of dominant single-gene disorders
Familial hypercholesterolemia (defective LDL receptors. If you are double negative for cholesterol receptors, you will most likely die in utero) Huntington's disease Achondroplasia Marfan's Retinoblastoma Li-Fraumeni
Examples of recessive single-gene disorders
Sickle cell anemia
Cystic fibrosis
Lysosomal storage diseases (Tay-sachs, gaucher, Niemann-Pick)
Glycogen storage diseases
Phenylketonuria (can’t convert phenylalanine to tyrosine)
Li-fraumeni syndrome involves a defect in this gene
p52 tumor suppressor gene
What is Tay-Sach’s disease?
Progressive deterioration of nerve cells and mental and physical abilities. Onset at 6mo, death usually by age 4. An enzyme is missing, resulting in collection of glycolipids in the brain.
What is an autosome?
A chromosome that is not a sex chromosome
Benefit of sickle cell anemia
Immune to malaria
This country has the highest incidence of CF
Ireland
How can we control if a gene will be used or not?
Methylation. By adding a methyl group to the 5 position of cytosine, chromatin condenses and inactivates the gene. This process is reversible. This process is called epigenetic modification.
Markers of cell death
LDH (lactate dehydrogenase) and creatine kinase
This lab value measures the extrinsic pathway
PT
This value measures the intrinsic pathway
APTT
The main problem in familial hypercholesterolemia is
Defective LDL receptors
______-_____% of head injuries are not severe
75-90%
