Infectious Disease Flashcards
What are the 3 types of microorganisms?
1) bacteria
2) viruses
3) fungi
What is the broad name/category for most bacteria in the body? What does this mean?
commensal bacteria
It lives symbiotically with you and causes no harm, its your own natural flora in gut, skin, vagina, etc.
Specifically, what type of bacteria is in our flora?
lactobacillus “good” bacteria
What do commensal bacteria secrete?
commensal bacteria secretes toll-like receptor (TLR) ligands which bind to TLR on the surface of normal intestinal tissue
Where does commensal bacteria bind to and what does this allow?
binds to the epithelium of the gut and allows signaling for repair, protection of injury, etc.
What does it mean for the body if TLR signaling is intact?
TLR ligands will bind to TLR and cause basal signaling
this leads to homeostasis of the intestinal surface and robust repair in response to injury
Describe what happens if TLR signaling is disrupted
TLR ligands will bind to TLR, but no signaling will occur/no activation of signaling
this will cause enhanced sensitivity to injury and diminished capacity to induce repair
What does it mean if there is no TLR signaling in the gut?
There are no ligands binding to TLR, so basal signaling is inactive and does not occur
this will lead to enhanced sensitivity to injury and diminished capacity to induce repair
What does basal signaling do in simplest terms?
protects against cellular injury
What is an example that may disrupt TLR signaling?
antibiotics can eradicate commensal bacteria which results in compromised ability of the intestinal epithelium to withstand injury and repair cell damage
What happens to the body if antibiotics disrupt your natural flora?
body will be more susceptible to bacterial infections, such as C. diff
What does C. diff cause?
Hint: think in terms of when the natural flora is disrupted through antibiotics
pseudomembranous colitis and candida overgrowth
Where in the body is it sterile (no commensal bacteria)?
blood, CSF, kidneys, bladder, female fallopian tubes/ovaries
How is infection typically transmitted?
through direct contact, such as touch or sex
or through fomites (inanimate objects such as medical instruments, bed linens, etc.
List at least 3 ways infections are spread
in no specific order:
1) needle or injury (direct access to blood)
2) bites, stings or worms (direct access to blood)
3) animals (vector-borne)
4) sexual intercourse
5) ingestion (contaminated soil/water, poultry, eggs, oral/nasal secretions, etc)
6) inhalation (oral/nasal secretions)
What is an example of infection that inhales microbes through nasal/oral secretions?
TB
What is an example of infection that uses a vector, or in other words animal/insect intermediate?
malaria
What is an example of a microorganism that can cross the placenta? What infection does it cause?
Treponema pallidum causes Syphilis
this can really infect the fetus and cause neuro damage or fetus can even die in utero
What are nosocomial infections?
any infection acquired within a hospital or medical facility
What is the most common nosocomial infection? What are the secondary infections that are also fairly common?
most common= staph causes UTIs
secondary= wound infections, pneumonia, or diarrhea
What is the most common serious nosocomial infection? Secondary infection?
most common= MRSA (Methicillin-resistant staphylococcus aureus)
second most common= C. diff
How easy is it for C. diff to enter the body? What happens once a pt has C. diff?
once the bacteria gets in the body, it’s very easy to get through the stomach (entrance is easy if pt is susceptible to infection)
C. diff causes pseudomembranous colitis, which results in diarrhea, abdominal pain, and high fever
What are the 3 ways bacteria can infect you?
1) secrete toxins
2) secrete enzymes
3) become spores
some bacteria can do more than 1 of these options
What are the toxins that bacteria secrete?
exotoxins or endotoxins
What type of bacteria typically secretes exotoxins?
Hint: it is either gram pos or neg
gram positive bacteria
How are exotoxins released/distributed into body?
they diffuse through tissues and in body fluids
What is an example of an exotoxin?
neurotoxins
What is an example of a neurotoxic bacteria?
Clostridium tetani (C. tetani)
What does C. tetani cause?
causes tetanus
it does not kill any cells, but rather enters the cells and disrupts metabolism
It inhibits neurons (this is called opposed neurons), where one neuron is fired off and the opposite neuron is inhibited
What is a classic sign of tetanus?
lock jaw which is caused from muscular rigidity because neurons are being inhibited and this impacts the muscles
What type of bacteria typically secretes endotoxins?
Hint: it is either gram pos or neg
gram negative bacteria
How are endotoxins released into body?
they are only released once/if the bacteria dies
What can release of endotoxins lead to?
minor symptoms such as fever, weakness, etc.
huge inflammatory response (release of lots of cytokines)
What happens if the body doesn’t take care of endotoxins right away?
the endotoxins will make it to the bloodstream and due to its huge inflammatory response, this can lead to septic shock
What are 2 examples of an enzyme that some bacteria can secrete?
collagenases (which break down collagen in the body)
hemolysins (break down RBCs)
What is a bacteria we learned in class that can secrete collagenases?
C. histolytieum
collagenases break down collagen, so in this case it will cause gas gangrene
Are bacteria spores hard to destroy?
YES!!!!! unfortunately
What are 2 examples of bacteria that can become spores?
C. tetani and C. botulinum
What bacteria did we learn in class that has multiple infectious routes?
C. tetani can secrete exotoxins (specifically neurotoxins) or become a spore, depends on the environment
Where does C. tetani typically form spores?
the soil
we can get infected by this through ingestion
What does C. botulinum cause? Where does it typically form spores?
causes botulism which can occur from eating expired canned foods or damaged/seal broken canned foods
Clostridium is just sitting there and eventually will cause illness because it can protect itself since it is a spore and it’s hard to destroy
What are viruses?
Hint: think in terms of microbiology
obligate intracellular parasites (have to get into your cells to infect you, viruses are not alive)
What are two types of infections viruses can cause?
chronic and latent infections
What is an example of a chronic viral infection?
Hep B
What is an example of a latent viral infection?
Varicella zoster (causes chicken pox and the latent infection you can get afterwards is shingles)
This is because it sits in the dorsal root ganglia and something must trigger the inactive virus to become active again after having chicken pox, and so this trigger can cause shingles
What is an example of a viral infection that has multiple strains?
the flu
T/F:
In some cases, viruses can change the DNA of cells in order to become malignant
True!
What is an example of a viral infection that can lead to change in DNA and malignancy? List a few cancers that it causes
HPV (human papillomavirus) most often leads to cervical cancer
It can also cause throat or oral cancer and this is common in both genders
What are the stages of infection?
1) incubation period
1A) prodromal period (only some pt)
2) acute phase
3 outcomes:
3A) full recovery or short convalescent period
3B) chronic infection
3C) death
What is the incubation period of infection?
it is the time from the pathogen entering the body to first sign/symptom onset
this is when the pathogen enters the body, colonizes, and multiplies
What is the prodromal phase of infection?
this is the stage after incubation period where SOME patients (not all) will experience mild symptoms of “not feeling well” or “coming down with something” but cannot actually pinpoint symptoms
What is the acute phase of infection?
this is when all signs and symptoms have manifested and its becoming evident that the pt has some type of infection
What are the 3 possible outcomes after the acute phase of infection?
3A) total recovery or a short convalescent period
3B) develops into chronic infection
3C) pt dies from infection
How long is the incubation period of infection?
anywhere from a couple days to weeks
How long is the prodromal phase of infection?
typically lasts only a few days
What does the acute phase of infection duration depend on?
pt immune system and/or medical intervention
acute phase length varies among each pt
What is the medical term for death from infection?
septicemia
If a pt has an acute infection and they begin to show signs of recovery what does this mean for the pathogen?
decreased reproduction and death of pathogen
host defenses take effect
nutrient supply decreases
wastes and cell debris increase
antibacterial drug
If a pt comes into your office with an infection, how are you going to correctly diagnose this?
Ex: you suspect pt has a wound infection, throat, or oral infection
options:
1) C&S (culture and sensitivity)
2) send pt home w/ broad spectrum antibiotics while C&S is being processed (or guess and give them something more specific)
3) blood culture
4) blood test (CBC w/ diff)
5) X-ray
What is a C&S?
take culture in office and send it to lab so they can test sensitivity
this will tell you what infection the pt has, what microorganism it is and what medication it is susceptible to
depending on microorganism it may take a few days to grow- (what should you do in this case? Send pt home with broad spectrum antibiotics or guess on microorganism if you have enough experience)
When should you do a blood culture if you suspect a pt has an infection?
only do a blood culture if you think the microorganism has entered the bloodstream
What blood tests should you be doing if your suspect a pt has an infection? What should you be looking out for?
do a full CBC panel w/ diff (this means WBCs, RBCs, and platelet count, as well as differential for each WBC type)
look out for:
- leukocytosis
-elevated neutrophils, lymphocytes, monocytes, CRP and SED rate, etc.
-leukopenia
-Abs
What is leukocytosis?
increase in WBCs, so if its elevated = infection
What do elevated neutrophil count mean?
acute infection
What do elevated lymphocytes/monocytes mean?
chronic infection
What is leukopenia?
decrease in WBCs/ WBC deficiency
What does CRP stand for?
C- reactive protein
What is another name for SED rate?
ESR- erythrocyte sedimentation rate
What does elevated CRP and SED rate mean?
some kind of inflammatory process
What are X-rays typically used for in terms of infection diagnosis?
pneumonia or TB
T/F:
only some microbes can infect the GI tract
FALSE
any microbe can infect GI tract
How long do most infectious diarrhea cases last? Does anything help it?
most last 2-3 days, OTC meds should help w/ N/V and diarrhea
What happens if you have infectious diarrhea for over a week? What is a major complication that can arise if left untreated?
leads to dehydration and electrolyte imbalance
complication: cardiac failure
Who is most vulnerable to infectious diarrhea?
elderly, young children, or immunocompromised
What are the 4 broad categories for GI tract infections?
1) environment
2) agent
3) host
4) site
What are the 3 environmental categories for GI tract infections (mode of transmission)?
1) water-borne
2) food borne
3) person to person (fecal oral spread)
What are the 3 agent categories for GI tract infections?
1) bacterial
2) viral
3) parasitic
What are the 3 sites for GI tract infections?
stomach, small intestine, large intestine
What type of diarrhea is produced through the small intestine if it is infected?
very copious amounts of watery diarrhea
ex bacteria that would cause this: V. cholerae
What type of diarrhea is produced through the large intestine if it is infected?
inflammatory or hemorrhagic diarrhea
Give an example on a bacteria that will cause diarrheal disease
Escherichia coli (E. coli)
name this bacteria:
a part of your bacterial flora, and if it overgrows it can cause diarrhea
Escherichia coli (E. coli)
How does gastroenteritis differ from E. coli diarrheal disease?
gastroenteritis also causes diarrhea but it is an infection of the stomach and upper portion of the small intestine
w/ gastroenteritis you will still have nausea and abdominal pain, but it can be treated quicker than infections in the lower GI tract
What is the most common cause of diarrheal disease in the world?
Escherichia coli (E. coli)
What is the most common cause of gastroenteritis in the US?
norovirus or rotavirus on cruise ships
What are the 3 types of infectious diarrhea? Where is this infection?
infection in small or large intestine
1) hemorrhagic diarrhea
2) secretory diarrhea
3) inflammatory diarrhea
T/F:
hemorrhagic diarrhea is actually a subcategory of inflammatory diarrhea
true
Hemorrhagic diarrhea is usually from an infection where?
large intestine
What bacteria usually causes hemorrhagic diarrhea?
Escherichia coli (E. coli)
How many toxins does E. coli produce? What do these toxins do?
E. coli produces 2 different types of toxins
these toxins can cleave your RNA and disrupt protein synthesis which ultimately kills the cells
What is the primary function of large intestine?
to absorb water
What happens to the toxins secreted from E. coli?
they will get into bloodstream and will undergo phagocytosis by neutrophils
for some unknown reason, neutrophils will also undergo endocytosis by the endothelial cells in the blood vessels
What happens once the toxins secreted from E. coli get into the walls of blood vessels?
it will start to destroy the walls of blood vessels
this will cause an inflammatory process called vasculitis
this is where bleeding comes from and why its called hemorrhagic diarrhea
Secretory diarrhea can be caused by….
1) bacteria (ex: V. cholerae)
2) viruses (ex: norovirus)
3) protozoa (ex: giardia)
What is giardia?
tiny parasite (germ) that causes the diarrheal disease giardiasis
If you drink/ingest contaminated water, you will most likely develop a _______ infection
hint: bacterial, viral, or protozoan
protozoan
if you drink/ingest contaminated water, you will most likely develop a protozoan infection
Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC) toxins have how many subunits? What are they called?
2 subunits: A and B
What two bacterias share a similar pathogenetic mechanism in causing diarrheal illness?
Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC)
How does Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC) bacteria gain entry into the body? How do they attack?
through ingestion of contaminated food and moves down the GI tract where it “attacks” in the small intestinal lumen
they release an enterotoxin that is composed of one A subunit and 5 B subunits
Describe process of A/B subunits in Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC) bacteria releasing enterotoxins?
The B subunits bind to the intestinal cell membrane and facilitate entry of part of the A subunit
this results in a prolonged activation of adenylyl cyclase and the formation of cyclic adenosine monophosphate (cAMP), which stimulates water and electrolyte secretion by intestinal endothelial cells
Where are GPCR typically found?
gut tissue
List the 5 textbook steps for GPCR-adenylyl cyclase signal transduction and amplification
1) signal molecule binds to GPCR, which activates the G protein
2) G protein turns on adenylyl cyclase, an amplifier enzyme
3) adenylyl cyclase converts ATP to cyclic AMP
4) cAMP activates protein kinase A
5) protein kinase A phosphorylates other proteins, leading ultimately to a cellular response
What does Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC) bacteria do to GPCR?
normal cell process (last step of normal GPCR)= once you activate the G protein, the A subunit is released and binds to something else
in bacteria= the toxin will signal to the subunit to bind to GPCR, GDP falls off and the subunit binds to adenylyl cyclase, but never leaves (it stays on continuously)
the toxin never releases itself from receptor, so then adenylyl cyclase converts ATP to cAMP
cAMP activates protein kinase A and carries out cell response, which in this case would be continuous activation of adenylyl cyclase, breakdown of ATP to cAMP, production of kinases and phosphorylations
this all keeps cystic fibrosis transmembrane regulator (CFTR) protein channels open continuously (obviously not good)
What is NKCC2?
its a normal pump within the body, stands for sodium potassium 2 chloride pumps
What are the 4 textbook steps for NKCC2 system in the lumen/intestinal cells?
1) Na+, K+, and Cl- enter by cotransport
2) Cl- enters lumen through CFTR channel
3) Na+ is reabsorbed
4) Negative Cl- in lumen attracts Na+ by paracellular pathway, water follows
How did we discuss NKCC2 system in class? Normal process only
chloride travels from interstitial fluid through the cell and out to the lumen, potassium enters cell from interstitial fluid and then back out to fluid
sodium pumps from fluid into cell, back out to fluid and then between cells (paracellular method=between)
there are so many anions leaving that Na+ follows, so water does too (because water always follows sodium)
What happens once the NKCC2 system is done?
hint: all chloride that was needed to be removed was a removed, now what?
the channels close and stop
How does Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC) bacteria affect the NKCC2 system? What does this lead to?
they keep the CFTR channels open continuously (Cl- always leaving, Na+ leaving and water always following)
copious amounts of water leads to an incredible amount of secretory diarrhea which destroys the cells and does not allow them to absorb water (hijacks the system)
this leads to volume/electrolyte depletion and dehydration, additionally, blood is primarily water, so when water is being depleted, blood is too and this causes a decrease in BP, in severe cases a pt can die from this
What is it called when there is lots of water loss with Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC) bacteria
hint: SECRETORY DIARRHEA
this is known as rice water stools because the diarrhea is so watery and white
What is the easiest treatment for secretory diarrhea caused from Vibrio cholerae (V. cholerae) and enterotoxigenic E. coli (ETEC) bacteria?
saline solution (IV bag)
List some S&S for inflammatory diarrhea
water loss & diarrhea (obviously)
FEVER (only one of the 3 types of diarrhea has fever)
usually the stool has mucus in inflammatory diarrhea
blood present = dysentery
What is dysentery most commonly caused from?
shigella and salmonella
What is dysentery? Talk about the process of infection
enterocytes enter the GI system, multiply, release toxins, and the cells die, which causes minimal water absorption & severe bloody diarrhea
Do cells die only from toxins (in the case of inflammatory diarrhea)?
NO- some cells die as part of inflammatory response, not just from the toxins!!!!
what type of infection is influenza?
viral infection
What antigenic shift type strain is most well known for the flu? Why? What is it? Talk about its significance
Type A H1N1
this flu strain had the largest number of recorded deaths in 2009
Type A H1N1 is one of the subtypes of type A
It was found to have genetic material from humans, pigs, and birds
Who is most susceptible to the flu?
children, elderly, and immunocompromised
RNA viruses are a part of what family of viruses?
hint: big umbrella term
myxovirus
What are the 3 subgroups for the flu?
type A, B, and C
Which subgroup of the flu is most prevalent?
type A
List some characteristics for type A influenza (flu)
most prevalent type
mutates a lot
can jump from species to species (this is called antigenic shift)
What does it mean for us if the flu virus can mutate so often?
we cannot develop a good immunity to it
we also end up playing catch up with the vaccine every time it mutates
How is influenza transmitted?
through droplets or indirect methods
What is the lifespan of RBCs?
approx 120 days
What is the lifespan of WBCs?
approx 1-3 days
What is the lifespan of neurons?
years
Cells have an elaborate system that detects changes in DNA. What are the 2 options in this case for once those changes are detected?
1) repair DNA
2) undergo apoptosis
When does neoplasia happen?
when the system for detecting changes in DNA fails and does not repair or force cells into apoptosis
What is apoptosis activated by?
intrinsic pathways in response to stressful or catastrophic cellular events or by the extrinsic pathway in response to a signaling instruction to cell death receptors
How do cancer cells suppress the apoptotic response?
by upregulating the anti-apoptotic proteins or downregulating the pro-apoptotic proteins
Epithelial cells are constantly undergoing turnover. What happens as you age?
with time, function will decrease and cells will die
What are benign tumors?
growth doesn’t affect organism overall or health, “normal” encapsulated cells
What are malignant tumors?
abnormal cells reproducing faster than normal cells, abnormal mitotic figures (under microscope), can invade tissues, metastasis or spread, can invade other tissues/organs, unorganized/abnormal cell shape
What are neoplasms (tumor)?
abnormal cell growth with abnormal architecture and sometimes loss of homeostasis
How does a benign tumor differ from a malignant tumor in terms of borders?
benign tumors are encapsulated with clear borders and are typically just an overgrowth of tissues, whereas malignant tumors are invading surrounding tissue and looks somewhat chaotic
What is the pre-clinical phase of neoplasia?
genetic abnormalities with proliferation of abn cells
pt cannot detect any issues (not sick, no S&S)
medical screening MIGHT catch something, but not always
What is the clinical phase of neoplasia?
symptomatic phase
What do ECM proteins do? What happens if they’re hijacked?
allow normal cells to adhere to something (most often cell-to-cell adhesion)
if they’re hijacked then this is how cells are invaded with cancer
What are non-neoplastic cell changes? Give an example
cell growth or changes that are not necessarily cancerous
ex: growing children, pregnant mama, ulcers, etc.
What may cause neoplastic cell changes?
stochastic events (random)
age
environment
OR DNA might mutate, but show no effect on the body (unknown cause)
What are the 5 deviations from a normal cell?
1) atrophy
2) hyperplasia
3) hypertrophy
4) metaplasia
5) dysplasia
Define molecular profiling
study of DNA/RNA changes in cells
What is the primary precursor for cancer?
hint: its a type of deviation from normal cell
dysplasia
Define atrophy of the cells
decrease in size of cells
Define hyperplasia of cells
increase in the number of cells
Define hypertrophy of cells
increase in size of cells
Define metaplasia of cells
converts to other cell types (this process is reversible)
Define dysplasia of cells
cells return to immature cell state (lack of differentiation)
What part of the immune system will respond to cancer first?
the innate immune system
Inflammation of normal cells, if prolonged, can promote….
tumorigenesis
T/F:
The inflammatory response can also contribute to tumorigenic growth once a tumor has developed
true!!!!
Chronic inflammation can cause/trigger cancer. What is the example we went over in class? Talk about it
IBD (inflammatory/irritable bowel disease) may cause ulcerative colitis long term, which can lead to colon cancer
The inflammatory response usually causes ______ of some enzymes
hint: upregulation or downregulation
upregulation
The inflammatory response usually causes upregulation of some enzymes
What are the 2 most common enzymes that are upregulated in inflammatory response?
COX1 and COX2
What is the function of COX1/2?
they catalyze the synthesis of prostaglandins (which also participate in inflammation)
What is the most common COX1/2 inhibitor?
celebrex, it’s an NSAID
Can the immune system detect cancer?
Yes, the immune system can recognize foreign peptides such as mutated residues from cancer cells
What immune system cell detects cancer?
activated cytotoxic T cells can identify some tumor cells expressing the mutated residue and kill them
Does the immune system have checkpoints like the cell cycle?
yes, these checkpoints are built in to restrain the immune system from over aggressive targeting
What interactions are involved in immune system checkpoints for detecting cancer cells? What is an example?
both stimulatory and inhibitory interactions
ex: PD-L1 by many tumor cells is a mechanism that enables them to suppress the cytotoxic actions of activated T cells and escape the immune system
What do cancer cells (and normal cells) need to grow?
nutrition! This comes from our food
What happens with cancer cells when they want to grow? What is the most common example?
They will release angiogenic growth factors that cause blood vessels to grow and give them more nutrients faster
the most common of these growth factors is VEGF (vascular endothelial growth factor)
What is normal cell metabolism with abundant oxygen? Does this generate a lot of ATP?
normal cells metabolize glucose using glycolysis followed by oxidative phosphorylation in the mitochondria when oxygen is abundant
this method generates plenty of ATP molecules compared to other methods and is more efficient
Describe (normal) cell metabolism with low oxygen
If the oxygen is limited, cells instead convert the pyruvate to lactate and increase the rate of glycolysis to generate ATP, although this is a far less efficient mode of generating ATP
Describe tumor cell metabolism
tumor cells convert pyruvate to lactate even when oxygen is abundant and thus have higher glycolytic rates to meet their energy demands. This observation is called the Warburg effect
What is an additional step tumor cells can do to make sure they have enough nutrients and grow?
use up amino acids in the body!
ex: serine and glutamine
What are the 3 different types of embryonic tissue?
ectoderm, mesoderm, and endoderm
Where are sarcomas derived from? What tissue is it? Give a few cancer examples
sarcomas are derived from mesoderms
this is connective tissue types of cancer
ex: bone, blood, muscle, cartilage cancer, etc.
Where are carcinomas derived from? What tissue is it? Give a few cancer examples
carcinomas are derived from ectoderms and endoderms
this is the most common type of cancer
this tissue type forms all of the epithelial tissues in body
ex of carcinomas: prostate cancer, breast, lung, colon, etc.
What is the best example of hyperplasia in normal cases?
pregnant mamas
What does carcinoma in situ/pre-invasive mean?
the tumor cells have not broken through the basement membrane yet
What does invasive carcinoma mean?
tumor cells have breached the basement membrane, goes into tissues underneath the membrane, can release collagenases (breaks down connective tissue so they can move through tissue more easily)
What does metastatic focus mean?
cancer cells have entered the circulatory system
T/F:
metaplasia is irreversible
FALSE
T/F:
dysplasia is irreversible, and once the cells multiply in this state it is considered neoplasia
TRUE
In breast cancer, what is the most common secondary cancers after the tumor cells metastasis?
breast cancer + liver or lung cancer
What cancer commonly spreads through seeding? What is seeding?
ovarian cancer
seeding happens primarily in body cavities and its when cells just break off and can move through the empty space
another method of seeding is when it is inadvertently done in a medical procedure (ex: attempting to remove tumor and cells are left behind that spread further)
What are the 8 stages of phenotypic changes in the progression of neoplasia?
1) genomic instability
2) enhanced proliferation
3) evasion of immune system
4) invasion of tissue and stroma
5) ability to gain access to and egress from lymphatics and bloodstream
6) establishment of metastatic foci
7) ability to recruit vascularization to support growth of primary or metastatic tumor
8) drug resistance
What are the characteristics of genomic instability in the progression of neoplasia?
impaired DNA repair and aberrant cell cycle checkpoint
What are the characteristics of enhanced proliferation in the progression of neoplasia?
-autonomous growth
-abnormalities of cell cycle control
-exaggerated response to hormonal or growth factor stimuli
-lack of response to growth inhibitors or cell contact inhibition
What are the characteristics of evasion of immune system in the progression of neoplasia?
-antigen modulation and masking
-elaboration of immune response antagonistic molecules
What are the characteristics of invasion of tissue and stroma in the progression of neoplasia?
-attachment of ECM
-secretion of proteolytic enzymes
-recruitment of stromal cells to produce proteolytic enzymes
-loss of cell cohesion
What are the characteristics of the ability to gain access to and egress from lymphatics and bloodstream in the progression of neoplasia?
-enhanced cell motility
-recognition of endothelial protein sequences
-cytoskeletal modifications
What are the characteristics of establishment of metastatic foci in the progression of neoplasia?
-cell adhesion and attachment
-tissue-specific tropism
What are the characteristics of drug resistance in the progression of neoplasia?
-altered drug metabolism and drug inactivation
-increased synthesis of targeted enzymes
-enhanced drug efflux
-enhanced DNA damage repair
What is the grading scale for tumors? What is 1 and 4?
1-4
1= differentiated cells
4= undifferentiated cells, anaplastic (different sizes/shapes), highly malignant
Pain is one of the stages of inflammation and can also be from growing tumors. What can this lead to?
obstructions (primarily in tubular organs such as respiratory airways and digestive tract)
Tissue necrosis is most common in which cancer?
oral cancers (ulcers + necrotic tissue)
What is cachexia?
severe weight loss/severe muscle wasting during cancer/treatment
If cancer/treatment affects the bone marrow, then the pt will develop…..
anemia
What is the most common initial sign of anemia?
fatigue
List some issues that may arise from cancer/treatment
-vasculitis
-thrombocytopenia (complication = hemorrhaging)
-anemia
-paraneoplastic syndrome (indirect systemic effects of neoplasms)
-hormonal changes
-cachexia (severe weight loss)
List some direct systemic effects of neoplasms
-vessel compression
-vessel invasion and erosion
-lymphatic invasion
-nerve invasion
-brain metastases
-spinal cord compression
-bone invasion and destruction
-bowel obstruction and perforation
-airway obstruction
-ureteral obstruction
-liver invasion and metastases
-lung and pleural metastases
-bone marrow infiltration
What is a cancer we learned in class that can produce 2 different hormones? What are the hormones and what will the patient present with on top of their cancer symptoms?
bronchogenic cancer can produce ACTH, which will lead to S&S of Cushing’s syndrome
can also produce ADH (antidiuretic hormone) which leads pt to manifest S&S of SIADH (syndrome of inappropriate ADH)
What is the pathologic tumor-node-metastasis (TNM) staging system for breast cancer? What does each letter stand for and list each stage
T= size of tumor
N= node involvement
M= metastasis
Stages:
1) when tumor is less than 2cm in diameter and is very localized
2) less than 5cm and nodes are involved
3) greater than 5cm and nodes are involved
4) tumor is LARGE, metastasis, and nodes are involved
What is the most common cancer based on lifestyle choices?
lung cancer from cig smoking
What are the treatment options for cancer?
chemo, radiation, surgery, immunotherapy, etc.
most cancer treatments are prophylactic methods (preventative)
Before you start any type of cancer treatment, what should you do?
handle all other medical procedures/problems, especially dental procedures
What are some additional sources cancer patients need on top of family and their regular treatment?
mental health therapy, nutrition counseling, physical therapy, etc.
What is a lumpectomy?
a lump is removed from the breast, typically when cancer is present but has not spread
What is a partial mastectomy?
removal of cancer/abnormal tissue from the breast and some normal tissue around it, but not the whole breast
What is a total mastectomy?
a surgical procedure to treat breast cancer by removing an entire breast
What is a modified radical mastectomy?
surgical removal of the entire breast including the breast tissue, skin, and nipple, and most of the underarm (axillary) lymph nodes
What is radiofrequency ablation (RFA)? What tumor is it typically used for?
it’s a procedure that utilizes CT scans and an ultrasound probe on the skin with electrodes that magnifies an ultrasound beam to the tumor area and destroys the tumors cells/surrounding tissue with heat/radio waves
this is most commonly done with liver cancer
What is a common complication with a modified radical mastectomy?
lymphedema!!!!
This is a motivational flashcard:
We have made it so far. We will do amazing on Exam 1! I love you! You got this
+ one point/gold star for good effort
What is the purpose of using radiation before surgery for cancer?
to attempt to reduce the tumor size and margins
What are the 3 types of radiation?
1) external beam radiation
2) brachytherapy (internal radiation)
3) proton beam therapy
What is the most common radiation protocol?
everyday for 6 weeks
What is the purpose of radiation after surgery for cancer?
to try to destroy any remaining cancerous tissues (this unfortunately also destroys regular cells and blood vessels - which decreases nutrients to tumor/healthy cells)
What is brachytherapy (internal radiation) therapy?
a procedure that takes little devices known as seeds that have radioactivity and are placed into the tumor region
this is used to treat cervical, prostate, and some types of breast cancer
List some side effects of radiation therapy
-fatigue
-lethargy
-depression
-anemia
-susceptible to infections such as pneumonia or septicemia
-susceptible to heavy bleeding (if this is severe reaction then radiation will need to be stopped)
Radiation of pelvic region w/ people of reproductive age will be told to….
store their eggs/sperm
Radiation can cause damage to epithelial cells. We talked about damage to the skin, blood vessels, GI tract, and hair follicles- what are the complications of this damage?
skin: may look like pt has sunburn
blood vessels: may result in vasculitis
GI tract: may result in nausea and vomiting
hair follicles: may develop alopecia
head and neck radiation may cause….
oral ulcers or xerostomia (dry mouth- which will lead to difficulty chewing and swallowing and this decreases nutritional intake)
Chemotherapy is a combination of drugs. What are they?
classified as antimitotics, antimetabolites, alkylating agents, and antibiotics
What is the most common therapy for Hodgkin’s disease?
chemotherapy, specifically ABVD therapy
What is the ABVD therapy frequency?
given to pt on day 1 and day 15, and then after that once a month until theres a decrease in tumor cells (will be adjusted as needed)
Why is ABVD given in sporadic measurements?
it’s such a high conc. of drugs that there will need to be a rest period so that the normal cells can have a little time to heal
What does the A stand for in ABVD therapy? What type of drug is it and how does it work?
A= adriamycin
it is an antimitotic and antitumor antibiotic drug
it works in the S phase of cell cycle where it will disrupt DNA synthesis/replication
What does the B stand for in ABVD therapy? What type of drug is it and how does it work?
B= bleomycin (also known as blenoxane)
it is an antitumor antibiotic and it works in the S phase of the cell cycle
Why are A and B of ABVD therapy called antibiotics?
Ex: penicillin is derived from fungus, same goes for antitumor antibiotics (it comes from a natural source)
For A/B of ABVD therapy, they come from streptomyces which is derived from soil fungus
What does the V stand for in ABVD therapy? What type of drug is it and how does it work? What is it derived from?
V= vinblastine (also known as velban)
it is a plant alkaloid drug and is derived from vinca (look at periwinkle flowers!)
it works in mitosis phase of the cell cycle by disrupting mitosis
What does the D stand for in ABVD therapy? What type of drug is it and how does it work?
D= dacarbazine
it is an alkylating agent and is nonspecific, which means it works in all phases of the cell cycle
How are side effects similar/different between chemo and radiation?
chemo has the same side effects of radiation BUT, nausea and vomiting is heavily increased in chemotherapy compared to radiation
What are the 2 hormonal drugs we talked about for cancer?
estrogen to slow down the progress of prostate cancer
hormone blocking agents such as estrogen blockers for breast cancer that is estrogen dependent
What is prednisone used for in cancer?
to decrease inflammatory processes
What is a drug ex with immune action for cancer? What is it/how does it work?
Herceptin binds to receptors on breast cancer cells and prevents them from dividing
this is considered an immunotherapy bc it binds to the cancer cells and triggers the body’s immune system for phagocytic cells to come in and take tumor cells through phagocytosis
What are antiangiogenic drugs for in cancer? What is the most common example?
prevent angiogenesis (won’t allow the blood vessels to increase in size and number)
most common ex: avastin inhibits VEGF
Where is basal cell carcinoma most commonly found?
on head/neck region due to sun exposure
What is the most common skin malignancy?
basal cell carcinoma
What is the typical age range for people diagnosed with basal cell carcinoma?
most common in people 40+ years old and fair complexion
How does a basal cell carcinoma lesion look like?
starts off as a papular lesion with raised margins and center will become ulcerated (this is called a “rodent ulcer”)
T/F:
ovarian cancer is considered a multifactorial disease
TRUE
What is one of the silent tumors we talked about in class?
ovarian cancer
What are the first signs of ovarian cancer?
abdominal area is increasing in size
changes in bladder/bowel function (this is because the increasing tumor size infringes on the organs)
What is the biomarker used for a number of cancers? What is it used for?
CA125 is used to gauge the response to treatment (look at the levels of CA125 and hopefully in time they decrease with treatment and treatment can be adjusted)
Do brain tumors in general affect all age groups equally?
yes, adults and children are affected equally
Are benign and malignant brain tumors equally damaging, or no? Why, or why not?
both are equally damaging because there is no space for the tumor to push out/grow because of the skull, so this will lead to lots of pressure in the brain
What are some of the first signs of brain tumors?
headache
drowsiness
impaired motor function
visual disturbances
Brain cancers rarely metastasis. Why?
because it’s already fatal
however, other cancers can metastasize to the brain easily (ex: lung, breast, liver cancer metastasis to the brain the easiest/most often)
If the tumor is on the cerebellum or brainstem….
then it is usually fatal bc of all the important centers in that region
What are the characteristics of glioblastoma multiforme?
necrotic tissue and hemorrhaging (eating the normal tissue away)
Where do lymphoid neoplasms originate from?
immature/mature T cells, B cells, and NK cells
What are the 3 types of hematologic cancers we talked about in class?
leukemia, lymphoma, and multiple myeloma
Where is leukemia derived from?
immature leukocytes
Where is lymphoma derived from?
mature lymphocytes
What is another name for multiple myeloma? What is it derived from?
plasma cells myeloma, derived from plasma cells
Where is Hodgkin’s lymphoma derived from?
lymph nodes, bone marrow, and other lymphoid organs
What are the characteristics of Hodgkin’s lymphoma?
characterized histologically by Reed-Sternberg cells
usually started in one lymph node and then progresses in an orderly fashion throughout body
occurs equally in men/women and between the ages of 20-40
What is the first lymph node that is most commonly infected with Hodgkin’s lymphoma?
cervical lymph node, it becomes enlarged but initially painless
What is the staging system called for Hodgkin’s lymphoma? What are the stages?
Cotswold staging system
1) 1 lymph node/area showing cancerous region
2) 2+ lymph nodes/regions involved, but all on one side of diaphragm
3) nodes on both sides of the diaphragm and the spleen is most commonly infected
4) metastasis (most commonly to liver and/or lungs)
S&S of Hodgkin’s lymphoma:
-infections become common
-pain throughout body
-pruritis throughout body
-weight loss
-fatigue
-anemia
-low grade fever
What is the best treatment option for Hodgkin’s lymphoma?
ABVD therapy (chemo)
What is non-Hodgkin’s lymphoma?
any lymphoma that is not Hodgkin’s lymphoma is considered non-Hodgkin’s lymphoma
Where does non-Hodgkin’s lymphoma most commonly develop?
in immunocompromised patients (ex: HIV pt)
What is non-Hodgkin’s lymphoma associated with?
viruses such as EBV and areas of chronic immune stimulation
ex: gastritis caused from Helicobacter pylori (H. pylori) can affect MALT (mucosa associated lymphoid tissue) and eventually develop into non-Hodgkin’s lymphoma
80% of non-Hodgkin’s lymphoma originates from…..
B cells thats express CD20
this lymphoma involves multiple lymph nodes throughout body and usually genetically predisposed (translocation of chromosome 14)
What is more difficult to treat non-Hodgkin’s lymphoma or Hodgkin’s lymphoma?
non-Hodgkin’s lymphoma is more difficult to treat
What are the 2 subgroups for non-Hodgkin’s lymphoma?
indolent non-Hodgkin’s lymphoma and aggressive non-Hodgkin’s lymphoma
What is indolent non-Hodgkin’s lymphoma?
slow growing, painless initially
What are the 2 examples for indolent non-Hodgkin’s lymphoma?
1) follicular lymphoma is caused from a translocation that results in overexpression of an oncogene that is going to inhibit apoptosis and this is very difficult to cure, however it is non-aggressive. Within 10 years of having follicular lymphoma, 50% of pt will go on to develop a more aggressive type
2) marginal zone lymphoma (MZL) is one subtype of the MALT type of lymphomas and it grows slowly but is treatable and lots of pt can undergo remission
Aggressive non-Hodgkin’s lymphomas are most often…..
incurable
What are the 3 examples for aggressive non-Hodgkin’s lymphoma?
1) mantle cell lymphoma is caused from a translocation that overexpression cyclin D1 (cyclin D1 activates cyclin dependent kinases that keep on G1 phase of mitosis), so mitosis is basically always on, however it is unknown why this is more prevalent in men specifically older men
2) diffuse large cell lymphoma is the most common subtype and has the worst prognosis (1/3 of pt go on to metastasis to bone or stomach cancer typically)
3) Burkitt lymphoma is associated with EBV
What does it mean if apoptosis is inhibited in cancer?
cells will keep multiplying and growing
What are the characteristics of multiple myeloma?
-punched out lesions
-primarily occurs in adults age 50+
-pt produce huge numbers of abnormal plasma cells/Abs
-multiple mutations in multiple genes
-the abnormal plasma cells accumulate in the bone, bone marrow, and soft tissue
-not producing normal Abs= more susceptible to infection
-anemia
-Abs are in bloodstream and kidneys filter through this- so, abnormal Abs can damage the kidneys and pt may go into renal failure
-Abs accumulating in bone = pressure buildup/pain
-osteoclasts break down bone so bones become weak and fracture easily
-as bones are broken down they release lots of calcium, so pt may suffer from hypercalcemia
-even with treatment. average survival rate is approx 3 years
MNEMONIC= CRAB
C= hypercalcemia
R= renal failure
A= anemia
B= bone fractures/lesions
Sepsis is a clinical syndrome characterized by….
a dysregulated inflammatory response to infection
What is the leading cause of morbidity and mortality in the US?
sepsis
What is systemic inflammatory response syndrome (SIRS)?
clinical syndrome that is a form of dysregulated inflammation and may be seen with infection as well as with noninfectious states such as pancreatitis, pulmonary embolism, and myocardial infarction
Sepsis generally starts with….
a localized infection
Define endotoxin
lipopolysaccharide (LPS) moiety contained in the outer membrane of gram-neg bacteria
it is composed of an outer polysaccharide chain the O side chain, which is a highly conserved lipid portion (lipid A) which is embedded in the outer bacterial membrane
Myocardial depression is a common finding in…..
early septic shock
Most patients who die of septic shock have either…..
refractory hypotension or multiple-organ failure
What are the 6 types of cellular DNA repairs?
1) base excision repair
2) mismatch repair
3) nucleotide excision repair
4) homologous recombination repair
5) non-homologous end joining
6) microhomology-mediated end joining
Loss of epigenetic control of chromatin is commonly seen in cancer cells, leading to….
abnormal expression of many genes, increased susceptibility to DNA damage, and errors in mitotic separation
What is aneuploidy regarding tumor cells?
tumor cells frequently have many more than the 46 chromosomes of normal cells
