Chapter 12 Cellular Physiology Flashcards
What is it called when nucleus shrinks and forms blebs?
pyknosis
What is it called when nucleus breaks into chunks?
Karyorrhexis
What is it called when the nucleus dissolves?
karyolysis
What is the marker for cell death?
phosphatidylserine
Who notices who is programmed for cell death?
Cyclin D (BigD!)
Who recognizes the label , attaches to it, and destroys the cell?
caspases
What is the gene in control of apoptosis?
p53
What labels proteins for destruction?
ubiquitin
If you see some part that should have apoptosed (i.e. webs between fingers, etc) what failed to happen?
apoptosis
In which event, apoptosis or necrosis, the cell membrane dissolves first, then the nucleus?
apoptosis
Which event, apoptosis or necrosis, involves inflammation?
necrosis
most common cause of necrosis
ischemia
9 types of necrosis
- ischemic
- purulent
- liquefactive
- granulomatous
- caseous
- fibrinoid
- fat
- gangrenous
- hemorragic
MC location of liquefactive necrosis
brain
What cause granulomatous necrosis?
virus, fungus, etc.. (T cells and macrophages)
caseous
TB!
Fibrinoid MCC in child
HSP
fibrinoid necrosis MCC in adult
HTN, diabetes
MCC of uremia in children
HUS
MCC of uremia in adults
HTN, diabetes
What are the signs of vasculitis?
schistocytes, bleeding from skin and mucosa; increased bleeding time
MC location of fat necrosis
pancreas (from chronic pancreatitis: damaged pancreatic cells release lipase that split TRI, forming free fatty acids that combine with Ca) and breast (after trauma)
MC cause of pancreatitis in children
trauma 2)coxsackie and mumps
MC cause of pancreatitis in adults
- gallstones 2. alcohol
What is the difference between dry gangrene and wet gangrene?
Dry gangrene from vasculitis because loss of blood supply; wet gangrene involves a superimposed infection
Which bacteria is responsible for gas gangrene?
clostridium perfringens
What bacteria is responsible for necrotizing fascitis?
MRSA
Where can hemorrhagic necrosis be seen?
any organ with dual blood supply: liver, brain, GI tract
treatment for abscess of lung
great surgically (drain) and IV antibiotics
Medication to relieve the symptoms of Peripheral Arterial Disease (PAD)
Cilostazol: prevents PLT aggression; dilate vessel
Main cause of monosomy or trisomy
nondisjunction
In which phase of cell division does nondisjunction occur?
anaphase (chromosomes do not properly separate or disjoin)
percentage of risk of any disease in the public
1-3%
chance of getting a disease with one risk factor (approximately)
10%
Chance of getting a disease with 2 risk factors?
(about 20% or more)
In which disease did the child inherit only one sex chromosome and manifests with webbed neck, cystic hygroma, gonadal streaks, widely-spaced nipples and coarctation of aorta?
Turner’s
In coarctation of the aorta, if the right upper limb has a strong pulse, but the left upper limb doesn’t, where is the coarctation?
proximal to L. subclavian artery
in coarctation of the aorta, if the upper limbs have strong pulses, but the lower limbs do not, where is the coarctation?
distal to left subclavian artery
If the child is pink proximal to nipples, but cyanotic distal to nipples, what kind of coarctation?
Coarctation proximal to left subclavian with a patent PDA which draws deoxygenated blood from pulmonary artery down into descending aorta (so lower limbs are cyanotic).
MCC of ASD in Down’s syndrome?
lack of septum secundum because no endocardial cushion
Which trisimony the child is born with rocker bottom feet, triphalangeal thumb, overlapping fingers, microencephaly, micrognathia
Edwards (trisimony 18)
Which trisimony the child is born with polydactyly, holoprosencephaly, GU problems, and possible omphacele
Patau (trisimony 13)
What are two possible later complications of Down’s syndrome?
ALL and Alzheimer’s
What is it called when neural crest cells failed to migrate to distal colon?
Hirschprung’s disease
Why early onset of Alzheimer’s in Down’s syndrome?
APP gene is on chromosome 21, unable to be cleaved to betalipoprotein E4
MOA Donepezil
inhibits breakdown of Ach via inhibition of acetylcholinesterase
MOA Memantine/Galantamine
blocks glutamate’s inhibitory effect on the NMDA pathway
Which checkpoint is there in the cell cycle from G1 to S?
Rb checks DNA, p53 induce apoptosis if abnormality found
Where else in the cell cycle does p53 initiate apoptosis if damage to DNA is detected?
G2 to M checkpoint
Why are patients predisposed to gout with any chemotherapy?
Destroying cells will cause purines to break down which will get converted to uric acid.
If you want to attack rapidly dividing nucleus, which vitamin should you take away?
folate, that’s why we have so many chemo that attack folate (i.e. Methotrexate)
Which drug should be given with methotrexate to prevent anemia?
leukovorin (folinic acid)
In which phase do we often use antimetabolites?
S phase (to inhibit DNA synthesis)
MOA of purine analogs (azathioprine, 6 mercaptopurine (6-MP); 6 thioguanine
inhibit de novo purine synthesis (put will make uric acid up, so give allopurinol)
What are the labs in tumor lysis syndrome?
K up, LDH up, uric acid up; Ca down, phosphate up; stone formation
MOA of Cladribine
inhibit enzymes involved in DNA metabolism, including DNA polymerase and ribonucleotide reductase
5 fluorouracil and cytarabine (ara-C) are examples of which class of chemotherapies
pyrimidine analogs
MOA of 5 FU
inhibits thymidylate synthase
MOA of ara-C
inhibits DNA polymerase
What is the difference between uracil and thymidine?
a methyl group
What is the methyl carrier
THF
Cyclophosphamide, Busulfan, Nitrosureas (Carmustine, Lomustine), Chlorambucil are all examples of which class of chemotherapies?
alkylating agents
We often use alkylating agents for which kinds of cancers?
slow growing, chronic such as MM and CLL
MOA cyclophosphamide
fat soluble, goes to liver, liver makes it water soluble by making free radicals, free radicals kill cancer, water soluble goes out kidneys, so it is harmful to kidney and bladder
MOA of cisplatin, carboplatin
kill cellls through cross-linking like alkylating agents
When is cisplatin used?
GU cancers (testicular, ovarian, bladder)
What is dacarbazine and procarbazine used for?
Hodgkin’s lymphoma
Doxirubicin, bleomycin, dactinomycine are all which class of chemotherapies?
anti-tumor antibiotics
What is doxirubicin used for?
leukemia, lymphoma
What is doxirubicin’s MOA?
inserts itself between DNA bases (intercalation); generates free radicals causing DNA breaks
What is Bleomycin used for?
Hodgkin’s, testicular cancer, squamous cell cancer
What is dactinomycin used for?
Wilm’s tumor (along with vincristine)
What class of drugs are vinblastine, vincristine, and paclitaxel?
microtubule inhibitors
What are vinblastine and vincristine used for?
leukemias, lymphomas
In which phase of the cell cycle does Paclitaxel work?
M phase; stuck in M phase
MOA of topoisomerase inhibitors
inhibit topoisomerase II (increase breakdown of DNA)
Which cancers are topoisomerase inhibitors used for?
testicular cancer, small cell lung cancer (etoposide); lymphoma (teniposide)
What are the markers for natural killer cells?
CD16, CD56
MOA of hydroxyurea
inhibits ribonucleotide reductase; used in CML and Sickle cell
MOA Bevacizumab
VEGF inhibitor; used in colon, lung, renal cell cancer
MOA of imatinib
tyrosine kinase inhibitor of BCR-ABL use in CML
MOA rituximab
antibody against CD20 receptor of B cells; used for CLL, IBD, Hodgkin’s
MOA of tamoxifen and raloxifene
SERM (Selective Estrogen receptor modulators) antagonist at breast and agonist at bone
MOA Transtuzumab
antibody against HER2, for HER2+ breast cancer
What SE do all “mabs” cause?
allergies, and cardiac fibrosis (eosinophils irritate myocardium)
What is dystrophic calcification?
calcification on lysosome destroys cell and release acid hydrolase which destroy RNA/DNA
(first N/K pump stops first, cell swells and Na/Ca pumps stop and Ca cannot get out and accumulates on lysosomes)
Which organelle breaks down fatty acids through beta oxidation?
peroxisomes
What guides protein into the rough ER?
pre-sequence (all get cleaved off)
What guides protein to Golgi apparatus? What is the “chaperone” ?
pro-sequence; HSP-90 (grab prosequence and sends to concave side of Golgi) ;
Which pro-sequence does not get degraded?
C peptide of insulin
What will Golgi add to proteins?
mannose 6 phosphate
Where is it sent after Golgi?
lysosome
What is the chaperone of a protein to the mitochondria?
HSP-70
problem of digoxin
blocks Na channels; sodium and Ca cannot get out; increases contractility but might cause Ca to build up on lysosomes, cause cell death
How long does it take for irreversible cell death in most tissues? in the brain?
6 hours; in brain 20 minutes