They retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types.

can differentiate into either a red cell, neutrophil or megakaryocyte.

The fluid portion containing water, proteins, and nutrients

-maintain homeostasis (fight infection, prevent bleeding)

-transport nutrients and electrolytes to cells

-carry waste products to kidneys, liver, lungs for excretion

refers to the fraction of blood volume occupied by red cells.

low hematocrit = anemia

Normally about 1/1000th as many in normal blood as red cells

Function: fight infection

1. Neutrophil (PMN): phagocyte (eats bacteria)

2. Lyphocyte - makes antibodies, recognizes and kills foreign cells (microbes, transplanted tissue, cells infected with viruses)

3. Monocyte: phagocyte, works together with lymphocyte to control immune response

4. Eosinophil: involved in allergic reactions, kills certain parasites

5. Basophil: involved in allergic reactions

What is the function of erythrocytes?

What is the function of T lymphocye (T cell)?

And where does it come from?

regulation of immune system

bone marrow, thymus, lymph nodes

What is the function of B lymphoctye (b cell)?

and where does it come from?

antibody production

bone marrow, lymph nodes, spleen, lymph follicles in certain other tissue

What are the functions of monocyte/macrophage?

Where does it come from?

1.phagocytosis (ingestion) of foreign cells, bacteria, etc.

2. Digests foreign molecules and transfers pieces to T cells, which then initiate specific immune response (tell B cells to make antibody)

3. Produces hormones (cytokines) which mediate inflammation and regulate growth of other cells.

Bone marrow (a first cousin of the neutrophil)

What is the largest lymphoid organ in the body?

spleen

anemia

decreased numbers of stem cells, macrocytic or normocytic anemia

-caused by agents that can damage or destroy stem cells:

1. cytotoxic chemicals

2. ionizing radiation in large doses

3. viral infection (rare)

4.  in most cases, cause cannot be found.

vitamin B-12 deficiency

-vitamin B12 is needed for DNA synthesis during red cell production.

-macrocytic with abnormal/delayed maturation (megaloblastic)

- treatment = B-12 injections

-may cause serious neurologic disease as well as anemia

-often due to stomach disorder causing decreased production of factor needed for B-12 absorption

"anemia of chronic disease"

-iron held in macrophages and not released to red cell precursors

- can be considered part of physiologic response to inflammation: bone marrow usually appears normal.  when inflammation gets better, so does anemia.

- normocytic or microcytic.

parents of individuals with sickle cell anemia have sickle cell trait- usually asymptomatic but their red cells can be made to sickle in the test tube (8% of African-Americans have sickle trait).

-mainly found in thos of African, Middle Eastern descent.

-have some resistance to malaria, which may account for the prevalence of the condition in this area of the world.

production of antibodies against one's own red cells (a mistake by the immune system)

-antibodies coat red cells, which are then eaten by macrophages in the spleen and destroyed.

-antibody coated red cells can be detected by the coombs test.

treatment- corticosteroids (suppress immune system), spenectomy (removes main site of RBC destruction).

foreign red cells enter bloodstream via a transfusion

The immune system makes antibodies to antigens on these cells.

ex: blood transfusion mismatch = antibodies are already present

blood transfusion match, but with some other foreign antigen = takes awhile for antibodies to appear. 

both organisms derive a benefit from the association

example: E. coli making vitamin k: needed for clotting

Commensal

the relationship doesn't help or hurt the host

harm/hinder the host

They are pathogenic

Describe Host Resistance

• refers to an organism's ability to fight disease
• Modified by the general state of health of the host (young/old, nourished)
• infection and disease are not synonymous: some people can harbor a parasitic organism and not get a disease.

Describe the iceberg concept of infection:

• of most of the infections occuring in the community, very few will come into awareness (most are subclinical) 

a= cellular response b=host response

Starting from the bottom of the pyramid and moving up:

1. Below visible change, subclinical disease

    a) exposure without cellular attachment or microbial proliferation.

    b) exposure without infection

2. Below visible change, subclinical disease

    a) microbe colonization and proliferation without apparent cellular damage

    b) infection without clinical illness (asymptomatic infection)

3. Discernible effect, clinical disease

    a) cell dysfunction with morphologic and biochemical deragements

    b) classical and severe disease, moderate severity, mild illness

4. Discernible effect, clinical illness

    a) lysis of cell

    b) dealth of organism 

What are some ways that cells react to infection?

• purulence (pus)
• generage lymphocytes and monocytes--> granuloma

1. Mechanical: skin, mucus membrane, body orfices, cilia (carry mucus up and out taking microbes away)

dilute the number of organisms present in the area and some secretions have anti organism activity

3. Epithelial: skin renews every couple of weeks, carries away bugs with it

4. Chemical: skin secreting compounds that are bacteriocidal, enzymes in the digestive system kill a lot of microbes

5. Microbial: normal flora...crowd out the bad bugs. 

• limit the spread of the agent
• destroy the agent
• prepare the area of damage for later repair

• first reponders among the leukocytes (white blood cells)
• non-specific
• react in a stylized manner
• phagocytize and engulf things

• innvolved in inflammation and immunity
• specific
• responsible for both humoral (antibody)immunity and cellular immunity

• antibodies are directed against an organism (antigen)
• sit on it, opsonization
• white blood cells recognize the antibodies
• white blood cells attack

• present in the mouth, GI tract, skin and vagina of many normal individuals
• in the impared host it can invade and cause disease (HIV, chemotherapy patients)
• facultative pathogen (opportunistic)
• usual cause of yeast infections
• Conditions it causes: yeast infections, oral candidiasis, thrush (organism grows in the back of the mouth)

inhibit chemotaxis

kill phagocyte 

inhibit lysosomal fusion

resist killing and multiply in phagocyte 

• inhibit production of phagocytes
• inhibit inflammation
• inhibit chemotaxis
• kill phagocyte
• inhibit phagocytosis
• inhibit lysosomal fusion
• resist killing and multiply in phagocyte
• reproduce quickly
  • genetic manipulation
  • exchange DNA: adapt resistance

1. Direct physical contact: sexual, mother-child, organism has to be present in moist environment
2. Indirect physical contact: eating utencil
3. Airborne Infection: sneeze
4. Food, water or soil-borne infection
5. Insect borne infection

*****Remember the 5 F's******

1. Fomites (can be coughed out)

2. Food

3. Fingers

4. Flies

5. Feces 

*** Remember 5 F's***

1. Fomites

2. Food

3. Fingers

4. Flies

5. Feces 

two general divisions of the immune system:

1. humoral immunity: concerned with antibody production

2. Cell mediated immunity: directs specialized cells to recognize and destroy offensive agents. 

toxins: may be made directly by the organism or be liberated when the organism is destroyed by the body's efforts to get rid of it

* some organisms are not toxic at all; however, the host's reaction to the invading agent may be very dramatic and normal structures that get in the way of the host's immunologic response end up getting damaged. 

What are some differences that prokaryotes have from eukaryotes along with distinguishing features of bacteria?

• smaller size
• absense of a nucleus and many other organelles
• ribosomes smaller than those present in a human cell
• a cell wall surrounding the cell membrane, similar to the cell walls of common plants
• lack many of the organelles found in "higher" eukaryotic organisms, but structures and enzymes are present enabling bacteria to exist as individual cells
• bacteria= complete organisms
• some bacteria surround their cells with a mucoid capsule (may augment their pathogenicity)
•  cell walls and capsules contain antigenic chemical compounds that can be recognized by the host, and the host can activate cells and produce antibodies and cell mediated reactions against these antigens.

1. Shape

• coccal-spheroidal
• bacillary-cylindrical
• Spirochetes-spiral shaped

2. Staining reactions

• gram stain reaction: gram + (purple), gram - (pink)
• acid fast stain reactions (important for mycobacterial infections)

3. cultural features

• grow them in large numbers in cultures...require: food, temperature, amount of moisture, amount of oxygen
• colony formation in culture: bacteria tend to form characteristic groups or colonies (size, shape, color and smell)
• oxygen tolerance: anaerobic (no oxygen), facultative anaerobic (with or without oxygen), aerobic (oxygen)
• biochemical properties: growth requirements (what bacteria need to grow), biochemical products (what the bacteria produce)

4. Immunotyping: using lab produced antibodies to join with and identify certain bacteria

5. antibiotic sensitivity: suppress growth (bacteriostatic action) or kill (bactericidal action)

6. DNA typing 

• majority of bacterial infections are caused by invasion of the host's tissue, often with permanent destruction of at least some of the tissue---> destructed tissue replaced by fibrous tissue (scar)
• examples: staphylococcus, pseudomonas, tuberculosis (TB)

- major problems and symptons are due to the effects of toxins elaborated by the bacteria

- examples: diphtheria, botulism, tetanus, cholera, traveler's diarrhea (turistas) 

problems encountered by the host are due to the sort of reaction the host mounts against the offending bacteria.

-cross antigenicity: rheumatic fever

-immune complex formation: post-streptococcal glomerulonephritis 

systemic disease caused by the presence of microorganisms or their toxins in the circulating blood.

- may be associated with chills, fever, fall in blood pressure due to vascular dialation, and poor cardiac function

- can ultimately lead to shock and death. 

-sepsis= systemic disease caused by the presence of microogranisms or their toxins in the circulating blood

- chills, fever, fall in blood pressure due to vascular dialation, and poor cardiac function.

-can also lead to shock and death 

- gram +, cocci

- grows in clusters

-examples: pimples, boils, abscesses,osteomyelitis, endocarditis, wound infections and food poisoning 

- doesn't spread itself 

-gram +, cocci

-certain streptococci are serious pathogens

-grow in chains

-ability to lyse red blood cells (hemolysis) in culture -

- detected usually by employing sheep red cells mixed with agar 

* alpha hemolysis: incomplete green hemolysis

*beta hemolysis: complete clear hemolysis

*gamma hemolysis: no hemolysis

***beta hemolytic group is the most dangerous 

- grows in pairs

-makes a capsule that protects it from being eaten by phagocytes

-gram +, cocci

- organism commonly lives in the nasopharynx

-may cause otitis media in children

- may be the reason for termial pneumonia in older adults. 

gonococcus: gonorrhea

meningococcus: meningitis

neisseria meningitidis: cause of spinal meningitis 

- gram negative cocci

- cause of spinal meningitis

- can infect the coverings of the brain and spinal cord with fatal results

- organism can colonize the nasopharynx of normal individuals

- hygiene, quick diagnosis and modern antibiotic therapy have made the difference. 

Clostridium: botulism, tetanus, gas gangrene

Corynebacterium: diphtheria 

- enterobacteriaceae: normal or disease causing inhabitants of the large bowel (E.coli)

-Shigella: gram negative non motile rods (cause bacillary dysentery) 

Enterobacteriaceae 

• enteric gram negative bacteria
• either normal or disease causing inhabitants of large bowle
• E.coli
• cause severe widespread infections in hopitalized and debilitated patients
• cell walls of these organisms contain endotoxins, when liberated these toxins can cause failure of the cardiovasular system, shock, and dealth

• gram negative nonmotile rods
• cause bacillary dysentery: acute infection of the wall of the large bowel and results in blood, pus, and mucus appearing in the stool
• damages bowel by direct invasion with resultant inflammation, plus the bacterium secretes an exotoxin which further irritates the bowel wall.
• dysentary is passed on by contaminated food and water, especially where human wastes are put into the source of drinking water.

- principally mycobacteria

- Tuberculosis: Mycobacterium tuberculosis

- acid fast bacilli

- thin long rod with a waxy coat 

- coat doesn't stain with ordinary gram stain

- doesn't grow on ordinary culture media

-slow growing organism 

• long slender helically coiled organisms
• Treponema palladium: syphilis
• Borrelia burgdorferi: lymes disease

• submicroscopic, subcellular agents with a protective coat of protein wrapped around a central core or nucleic acid.  There may be a surrounding lipoprotein envelope.
• they are obligate intracellular parasites
• can't reproduce outside of a host
• they do not multiply by dividing
• evolved mechanisms for invading a host cell and taking over the cell's synthetic machinery for the sake of viral reproduction
• nucleic acid may be RNA or DNA, but never both
• are classified by the type of nucleic acid they contain, their size, and the type of tissues they tend to infect
• viruses may spread by:

-lysing the host cell and releasing numerous progeny

-budding off from the host cell in a more controlled manner

-viral genomics becoming incorporated into the host genome and remaining dormant through mitotic cycles involving the host's genome.  

• viruses are implicated in causing certain forms of cancer
• viruses tend to be antigenic and induce humoral (antibody) and cell mediated immune responses 

• plant-like but do not have the photosynthetic machinery needed to generate sugar from sunlight, carbon dioxide and water
• live off of dying material or parasitize other organisms to survive.
• yeast, mold

1. Kingdom

2.Phylum

3. Class

4. Order

5. Genus

6. Species 

1. heat fixed bacterial smear
2. crystal violet and iodine
3. alcohol rinse
4. safranin counterstain
5. final water rinse

1. heat fixed bacterial smear
2. carbolfuschin
3. acid alcohol
4. loeffer's methylene blue
5. final water rinse

• natural passages
• via trauma
• via circulation

- bacteremia: the presense of viable bacteria within the blood (brush teeth)

- sepsis: the presense of various pus forming organisms or their toxins in the blood. 

Shock

Initial event in the development of a Neoplasm

(Benign or Malignant)

first step in the process of becoming a malignant cell.

Autonomous, dysregulated proliferation

repair mechanisms can become saturated and mutations can become fixed in the genome leading to transformation.

Replicative error results in increased mutations in the cells DNA during proliferation

an abnormal proliferation of cells that show the life threatening propensities of local invasion and distant spread (metastasis)

--malignant neoplasm

Cancer is a disease of the GENOME/DNA through mutations in somatic cells and rarely inherited through the germline (germ cells) which would show a mendelian pattern of inheritance

Carcinogenesis is a.....

Single Step or Multi-Step process???

Multi-Step

--no single mutation to an oncogene or tumor suppressor gene can fully transform a cell...requires multiple oncogenes and 2+ tumor spressor genes

5 Molecular Features of Cancer

1. acuisition of self-sufficiency in growth signals

2. insensitivity to growth inhibitory (antigrowth) signals

3. evasion of rogrammed cell death (apoptosis)

4. sustained angiogenesis

5. tissue invasion and/or metastasis

--most also show alterations in DNA repair genes and/or genomic instability w/ abnormal # of chromosomes.

Targets of genetic damage

(leading to carcinogenesis)

Normal cellular genes that promote growth and differentiation

Are mutations in proto-oncogenes:

loss of function or gain of function

AND

dominant or recessive?

gain of function

dominant

--once proto-oncogenes are mutated, they are called cellular oncogenes

growth factors

what are they and what can mutations cause?

soluble or cell surface proteins that lead to increased cell proliferation

mutations in genes encoding growth factors results in increased cellular proliferation BUT a single growth factor mutation is not enough to result in a malignant neoplasm

Growth factor receptors

What are they and what do mutations do?

membrane bound proteins that have an extracellular domain to bind growth factors

mustations can lead to activation without lignand (unregulated growth promoting signal to the cell and increased cell proliferation)

Signal transducing proteins

what do they do?

mediate signals from the cell surface to the nucleus

example: RAS

RAS

what is it's nickname and what does it do?

It is the signal transducing 'gatekeeper'

It is involved in mediating the growth promoting signals of many growth factor receptors.

Activation (by GTP) activates the MAP kinase-signaling pathway

RAS

what is the common mutation?

Nuclear ranscription factors

What do they do?

Cell Cycle: Phases and what regulates?

G1 - pre-DNA synthesis

S - DNA synthesis (cell commits to division

G2 - pre-Mitotic

M - Mitosis

G0 - quiescent cells that are nonproliferating

Regulated by: Cyclin-dependent Kinases (CDKs)

 and Cyclin D (major in G1 to S transition)

Proto-oncogene to cellular oncogene mechanisms

(3)

1. Mutational activation

2. Chromosomal translocations

3. Transcriptional activation

Mutational activation

converts proto-Onc to Onc

--single mutation results in a change in structure of gene product.

ex: point mutation, frameshift mutation

converts proto-Onc to Onc

--a portion of one chromosome can become attached to a portion of another chromosome

converts proto-Onc to Onc

--can occur through translocations (like in chromosomal translocation) or by gene amplification

Tumor supressor gene

what do they do?

growth inhibiting gene

they prevent normal cells from proliferating too fast

Mutations in tumor suppressor genes result in:

loss of function OR gain of function

AND are

dominant OR recessive

mutations?

Loss of function

AND

Recessive

APC, Rb (retinoblastoma gene), p53

p53

what is it?

mutations: loss or gain of function? dominant or recessive?

tumor supressor gene

***Most common target for genetic alteration in human cancers**

loss of function, recessive

"guardian of the genome" "gatekeeper of cell proliferation"

gram negative

gets into tissues through sexual contact

scaring of tissue

males=urination problems

females: infertility

pelvic inflammatory disease 

occurs in crowded conditions (ex: dorms)

rapidly spreading 

coats surface of brain

therapy is needed quickly

immunization availability 

clostridia 

dyptheria 

• gram -
• nonmotile rods

• cause bacillary dysentery: acute infection of the wall of the large bowel, results in blood, pus and mucus appearing in the stool
• microorganism damages the bowel by direct invasion with resultant inflammation, plus the bacterium secretes an exotoxin which further irritates the bowel wall
• can cause dehydration, anemia
• disorder is prevalent in the tropics

• cramping, ulcers 

improvement in sanitation

personal hygene 

• thin, long rod with waxy coat
• does not stain with gram stain
• acid stains and special media are needed
• slow growing
• can't transmit through blood exchange, only through inhalation
• aerobic (they love them some oxygen!)

• organism gets in body, usually through inhalation
• early neutrophilic response: the bacteria are ingested by neutrophils, but the bacteria multiply and the neutrophils die
• monocytes then engulf the bacteria, but also cannot kill it
• the monocytes that contain the bacteria go to regional lymph nodes
• within 1-2 weeks, cell mediated immunity starts up: testing for delayed hypersensitivity by skin testing will be positive
• organisms are slowly destroyed
• monocytes (macrophages) assume an epithelioid appearance and a granuloma (tubercle) forms with general necrosis (caseation)
• eventually most of the tubercles are walled off by scar

Primary Tuberculosis:

• If the cell mediated immunity does not function properly the bacteria may spread within 10-14 days
• may cause severe destructive pneumonia and disseminate throughout the body causing small foci of infection

• in some primary complex lesions the organisms may remain dormant
• later if the hosts cell mediated immunity becomes impared the bacteria may break out
• most cases are pulmonary with destructive disease
• also possible that there is hematogenous spread throughout the body, spread to GI tract by swallowing infected secretions, and spread to lymph distand nodes 

VERY CONTAGIOUS

spread via respiratory droplets during coughing, sneezing, talking 

Treponema palladium

(this is a spirochete) 

*long slender helically coiled organisms

*Treponema palladium (syphilis)

*Borrelia burgdorferi (lymes disease) 

-Nucleic acid core surrounded by a capsid

-the capsid is surrounded by an envelope 

-on the envelope there are envelope antigens 

• submicroscopic, subcellular agents with a protective coat of protein wrapped around a central core of nucleic acid
• there may be a surrounding lipoprotein envelope
• obligate intracellular parasites
• cannot reproduce outside a host cell
• do not multiply by dividing
• take over the cell's synthetic machinery for the sake of viral reproduction

may be RNA or DNA

NEVER BOTH! 

• lysing the host cell and releasing numerous progeny
• budding off from the host cell in a more controlled manner
• viral genomes becoming incorporated into the host genome and remaining dormant through mitotic cycles involving the host's genome. Some may just enter the cytoplasm of a host cell and remain inactive.  They may reactivate and form infectious viral particles at a later time.

human papilloma virus

- the DNAor products of human papilloma virus, types 16 and 18 (and others) are often found in association with dysplasias and/or carcinomas of the uterine cervix 

Kingdom

Phylum

Class

Order

Genus

Species

(Kinkie patty classes out green spandex) 

• attachment to the cell
• Penetration of the cell
• Unwinding of DNA
• Transcription of mRNA
• Translation of early proteins
• Replication of viral DNA
• Transcription of mRNA
• Translation of late proteins
• Assembly of viruses
• Release from the cell

• highly contagious infection of the respiratory tract
• viral proliferation occurs in the upper respiratory tract and trachea
• in most patients the illness is relatively benign, but may be complicated due to pneumonia
• influenza virus kills respiratory epithelium and destroys the barrier, giving bacteril parasites an opportunity to cause an additional infection (SUPERINFECTION)
• spherical
• has two antigens on its surface: a hemagglutinin and a neuraminidase
• able to change surface antigens (this is why there are new strains of flu)

 a secondary infection

- example is in viral influenza when the virus kills respiratory epithilium and destroys the barrier, giving bacterial parasites an opportunity to cause an additional infection. 

- hemagglutinin and a neuraminidase

*able to change surface antigens (this is why there always new strains of the flu) 

• big kid killer
• most frequent cause of viral gatroenteritis in the young
• may be the biggest killer of the young (BABY KILLER!)
• malnourishment
• GI infection

polio

rabies

encephalitis

"aseptic meningitis" 

diagnosis of viral infection can be made by viral culture, measuring host antibody production, and/or clinical picture

• plantlike: but lack pigments to generate sugarfrom sunlight
• live by saprophytic or parasitic means
• two forms of fungi: yeast and molds
• fungi live off of dying material or parasitize other organisms to survive

- a type of fungi found in warm, moist environments

-unicellular

-reproduce by budding 

-fungi

- live in colder, dryer environments

-exist as a mass of tubules that tend to form terminal spores or conidia

- long branching tubular hyphae which consist of several cells lying end to end and reproduce by apical growth of hyphae 

what fungal infections are known as

immune system

- in fungal infections damage to the host is not caused to any great extent by the invasive or toxic properties of the fungus, but rather the overwhelming destructive response of the immune system as the body tries to get rid of the parasite

ring worm: cause suerficial infections with a predilection for keratin rich structures such as nails, hair and epidermis

athletes foot and jock itch

• Fungi 
• part of the normal mouth and GI flora
• may involve mucous membranes and cause oral lesions (thrush) or vaginitis (especially in diabetics and pregnant women)
• In hospitalized or immunosuppressed patients it is an occasional cause of systemic illness leading to septicemia, endoarditis, meningitis, renal infections, and death

• ubiquitous mold usually associated with decaying vegetation but can be found everywhere
• has been recovered from air conditioning units
• can cause pulmonary infections and one of the more common opportunistic infections
• in severe infections it tends to invade and block blood flow and death of the tissues supplied by the vessel
• it may colonize and invade wounds or burns

• protazoa infections are common in less developed areas of the world
• unicellular, eukaryotic (possess nuclei, mitochondria and other organelles)
• some have very complicated life cycles, while others reproduce by asexual division (binary fission)

1. Luminal parasites (gastrointestinal and genitourinary): passed either directly from human to human or by contaminated food or water (fecal-oral transmission); related to inadequate hygen and sanitation

2. Blood and tissue parasites: generally transmitted via an arthropod (misquitoes, flies, etc)either a vector or secondary host- and more dependent on ecological factors allowing existence of vectors.

-tissue invasion

-tissue colonization

-due to host defense responses

How are protozoan infections diagnosed?

-protazoan disease

- caused by Entamoeba histolytica

-disease caused by ingestion of contaminated food or water

-organism lives in the colon and usually causes diarrheea (amebic dysentery); can spread to other organs including the liver, lung and brain

-organism is identified in stool smears as an amoeba that tends to phagocytize red blood cells or more often as a multinucleated cyst.

What protazoan organism is identified by its tendency to phagocytize red blood cells and often shows up as a multinucleated cyst?

What disease does it cause?

Organism: Entamoeba histolytica

Disease: Amebiasis

-protazoan disease

-caused by a species of Plasmodium

-one of the most widespread of all infections

-spread by the bite of infected female Anopheles mosquitoes: the organism reproduces asexually in man and sexually in misquito.

- spreads from the bite site to the liver

-spreads from the liver to the red blood cells

-fever, shaking chills, anemia, and plugging of small blood vessels

-has been transmitted by blood transfusions

fever

shaking chills

anemia

plugging of small blood vessels

-produces a flask shaped ulcer in the colon wall

-associated with bad sanitation

-protazoan

-causes amebiasis: disease is caused by ingestion of contaminated food or water

-tends to phargocytize red blood cells

-shows up most often as a mutlinucleated cyst

• uncommon in urban industrialized areas
• large, multicellular organisms including: roundworms, tapeworms, and flukes
• most have complicated life cycles
• high association with poor sanitation
• can cause disease by a variety of mechanisms: tissue invasion, host response, or competition between the worm and the host for nutrients
• worm infestations are often associated with high eosinophi count
• diagnosis is usually made by identifying the worm in stool or tissue

- pinworm

-worldwide distribution

-mainly an infection of children

-lives in the small and large intestines

-transmission by the fecal-oral route

- at night adult females migrate from their normal home in the colon and deposit eggs on the perianal skin

-the eggs cause inflammation and intense itching

-worms are occasionally passed in the stool, appearing as white moving threads

-relatively mild disease

1. Heart disease

2. Cancers

3. Cerebrovascular diseases

4. Chronic obstructive lung diseases

5. Accidents

What are the leading cancers in adult women?

1. breast

2. lung

3. colon and rectum

4. uterus

5. lymphoma/leukemia

1. lung

2. breast

3. colon and rectum

4. lymphoma/leukemia

5. pancreas

6.ovary

1. prostate

2. lung

3. colon and rectum

4. lymphoma/leukemia

5. urninary bladder

1. lung

2. prostate

3. colon and rectum

4. lymphoma/leukemia

5. pancreas

1. accidents

2. cancer

3. congenital abnormalies

4. homicide

5. suicide

*cancer types that are common in children are different from those that are common in adults

a swelling

-therefore, the term tumor could be applied to any type of swelling including  purely inflammatory process

-most people use this term to imply a swelling due to a neoplastic process

- the terms tumor and neoplasm are more often used interchangably

a heritably altered, relatively autonomous growth of tissue

- generally means "new growth"

too many red cells (the opposite of anemia)

the blood is too thick when hematocrit rises above 55%, tendency towards thrombosis. 

there is no good way to treat it, so it must be prevented!

-give anti-Rh serum to mother during delivery to prevent sensitization by Rh positive cells.

-Do not ransfuse an Rh negative woman with Rh positive blood 

1. Polycythemia vera (primary polycythemia)

- a form of myeloproliferative disorder, a low-grade neoplasm.  Red cell progenitors proliferate independent of normal controls.

-Treatment : phlebotomy (removal of blood), antineoplastic drugs.

2. Secondary Polycythemia

-Red cell progenitors proliferate in response to erythropoietin.

-decreased oxygen delivery to kidney -> increased production of erythropoietin by kidney -> increased red cell production

-usually caused by chronically low blood oxygen level due to lung or cardiac disease, may be correctable by giving oxygen. 

When mutation in DNA occurs, p53 is activated

It binds to DNA and upregulates the transcription of p21, inducing the cell in G1 phase AND it upregulates GADD45 (a DNA repair gene)

If DNA cannot be repaired, p53 can increase transcription of bax (pro-apoptotic gene)

programmed cell death that eliminates cell from the organism

involves the breakdown of cytoplasmic and nuclear skeletons, extrusion of cytoplasm, chromosome degradation, and nuclear fragmentation.

1. soluble cell surface death signals produced in a response to certain cytokines bind to cell surface receptors

2. intracellular sensor molecules (such as p53) detect one of the following: DNA damage, abnormal oncogene activation, survival factor insufficiency or hypoxia, and this can activate apoptosis

Cytochrome-C (a catalyst of apoptosis)

Aplastic anemia or other forms of marrow failure

Temporary drop in production due to bone marrow suppression by cancer chemotherapy.

OR you may have INCREASED NEUTROPHIL CONSUMPTION.

- Autoimmune

-Severe infections

- Enlargement of spleen 

1. soluble proteins and their receptors

2. Integrins and adhesion molecules that mediate matrix and cell-cell associations

VEGF - vascular endothelial growth facor

FGF1 and FGF2 - fibroblast growth factor 1 and 2

Tumors often give these off to initiate angiogenesis so that the tumor can receive more blood and oxygen

in response to physiologic stimuli (infection)

- neutrophils are normally stuck to the wall of blood vessels, ready for entering the surrounding tissue if needed, but with corticosteroid drugs, the neutrophils become less sticky and are involved in "demargination." - blood test says more WBCs but there are actually less to fight infection.

-neoplastic conditions that cause unregulated production of neutrophils. 

Steps in invasion of the extracellular matrix

Detatchment of the tumor cells from each other

Attachment to the extracellular matrix

Degradation of the matrix

Migration of the tumor cells

Classes of molecules involved in invasion and metastasis (2)

1. cell-cell adhesion molecules (CAMs, cadherins, integrins)

2. extracellular proteases

chemicals, radiation, some microorganisms (viruses)

**mutations could also be inherited

Acute vs. Chronic leukemia

What is acute leukemia caused by? 

Acute vs. Chronic leukemia

What is chronic leukemia caused by? 

acute lymphoblastic (or lymphocytic) leukemia (ALL)

-fatal if not treated, but it's OFTEN CURABLE.

-especially w/ children w/ chemotherapy and or marrow transplant. 

1. Initiation

2. Promotion

3. Progression

-ONCE A MUTATION HAS BEEN FIXED IN THE CELL IT IS SAID TO BE INITIATED

-mutation to single cells

-irreversible

-dose dependent (higher dose of carcinogen is more likely to induse a mutation

-some critical genes that mutation results in initiation include: oncogenes, tumor supressor genes, DNA repair genes, and apoptosis regulating genes

malignant proliferation of immature granulocye (or occasionally erythroid or megakaryocyte) precursors (blasts) leading to accumlation in blood, bone marrow, and often other tissues. 

-Proliferation is more rapid than in CML because blast cells divide faster than stem cells. 

-most common adult leukemia 

-THE ACCUMULATION OF ADDITIONAL MUTATIONS 

-reversible (since it doesn't involve a DNA mutation)

-involves exogenous signalling to the initiated cell

-dose dependent (more promoting agent = greater proliferation)

malignant proliferation of myeloid stem cell, with overproduction of white cells and often platelets.

- associated with specific chromosome mutation "Philadelphia chromosome" so that parts of the two different chromosomes get studck together and create new (hybrid) gene, which produces a protein that causes uncontrolled growth of myeloid cells. 

-ADDITIONAL DNA DAMAGE BEGINS TO ACCUMULATE MORE RAPIDLY (UNTIL THE MALIGNANT PHENOTYPE APPEARS)

-final, irreversible stage

-involves acquisition of multiple additional mutations and results in genetic instability

primarily affects older people, has slowly growing cells, and is treatable, but NOT CURABLE.

-cell of origin: B-cell and slowly growing, mature appearing cells that may take years to accumulate to the point that they cause symptoms. 

must be metabolically activated to an electrophile

indirect acting carcinogens

weak initiators

include alkylating agents

Radiation carcinogenesis

What are the divisions of radiation?

radiation induces DNA damage

1. Electromagnetic spectrum (ultraviolet, gamma, X-rays)

2. particulate radiation (alpha nd beta particles, protons and neutrons)

cause enlargement of lymph nodes, spleen, often infiltrate bone marrow and other tissues.

Some types cause leukemia

Most are treatable, some can be cured. 

ultraviolet A (320-400) is very low risk

ultraviolet B (280-320) is very high risk

ultraviolet C (200-280) is very high risk

fast growwing, immature appearing cells, curable with chemotherapy in 30-40% but many patients die of disease within 1-3 years. 

Example : diffuse large cell lymphoma. 

VERY fast growing, very immature (blast-like) cells similar to acute lymphoblastic leukemia.

Example: Burkitt lymphoma. 

distinctive microscopic appearance, with characteristic  large multinucleated cells (Reed-Sternberg cells).  Cell of origin not known but thought to be a lymphocyte of some kind.

One of the more common types of cancer in adolescents and young adults. 

Stage I - diseaes confined to single lymph node or group of nodes.

Stage II- disease in two or more lymph node groups on same side of diaphragm.

Stage III - disease in lymph nodes on both sides of diaphragm.

Stage IV- spread outside the lymph nodes (eg. bone marrow, liver, bone, etc)

Most patients with Hodgkins Disease

CAN BE CURED. 

1. intensity of exposure

2. quantity of radiation absorbed (melanain content of the skin is protective)

3. person's genetic makeup

a disease of plasma cells secreting monoclonal immunoglobulin, causing destruction of bone (holes in bone) and is NOT CURABLE!

happens in individuals over 40 

marrow infiltration may cause anemai, etc. 

1. the major changes that occur in neoplastic cells are genetic changes (i.e. DNA, mutations)

2. These changes are irreversible

3. These changes are transmitted to a cell progeny (daughter cells) 

1. neoplastic cells are not under the usual "rules and regulations" of most cells, so they grow with little regard to the rest of the organism (remember that pic of the lady with the f'd up grill)

2. Neoplasms are not completely self-sufficient: they require host blood supply to grow to clinically important sizes.

-most tumors outgrow their blood supply and become negrotic in their centers  

- less virulent

-not totally free of disease

-slow growing

-do not spread to other tissues

- general suffix "-oma" 

-non-invasive

-encapsulated

-no metastasis

-slow growth

-well-differentiated

-mature-looking cells

-rare mitosis

-localized 

- rapidly growing

-potential to spread throughout the body

-malignant neoplasms are commonly referred to as cancer 

-invasive

-non-encapsulated

-metastases

-rapid growth

-poorly differentiated

-anaplastic

-mitosis common

-invade to other tissues 

- local effects (e.g. erosion of bone leading to pathologic fractures or increased intracranial pressure leading to brain herniation)

-hormones that affect other tissues (e.g. a pituitary adenoma producing prolactin which stimulates the growth of breast tissue)

- pain

-bleeding 

- neoplasm=new growth; a heritably altered, relatively autonomous growth of tissue

*heritably altered: an irreversible genetic (DNA) alteration that gives a cell some growth advantage is transmitted to daughter cells during mitosis

-transformed cells are:

1.no longer very responsive to their environment (i.e. do not respond to signals to quit growing)

2. Are genetically unstable, so they accumulate more genetic alterations which allow them to further evade the immune system, grow autonomously and spread throughout the body

- neoplasms growth with little regard to the rest of the organism: the cells do not respond to signals put out by other cells and by the extracellular matrix to stop growing

-relatively autonomous:

-- the transformed cells are dependent on the surrounding tissue, or the "host" for oxygen

-- central necrosis occurs at the neoplasm outgrows the host's blood supply

--some neoplasms acquire a growth advantage by developing the ability to grow their own vessels. (angiogenesis or neovascularizatoin) 

-- the transformed cells may respond to some degree of growth-stimulating influences, such as hormones or growth factors 

- the transformed cells are dependent on the surrounding tissue, or the "host" for oxygen

- central necrosis occurs as the neoplasm outgrows the host's blood supply

-some neoplasms aquire a growth advantage by devleoping the ability to grow their own vessels (angiogenesis or neovascularization)

-the transformed cells may respond to some degree to growth-inhibiting or growth-stimulating influences (such as hormones or growth factors)

**this property can sometimes be used for therapeutic purposes (some forms of breast cancer are stimulated to grow by circulating estrogen, administration of an anti-estrogen, tamoxifen, blocks the ability of estrogen to promote the growth of the neoplastic cells)

a malignancy arising from epithelial cells

(e.g. squamous cell carcinoma or adenocarcinoma)

a malignancy arising from mesenchymal cells

(e.g. osteosarcoma, chondrosarcoma) 

-characteristic on the basis of clinical and histologic features.

- clinical feature used to determine whether a neoplasm is benign or malignant is the potential of the neoplasm to metastisize or move to lymph nodes and other organs.

**in general benign neoplasms stay confined to the tissue of origin, while malignant neoplasms have the potential to move throughout the body

that the malignant cells be able to degrade the surrounding tissue, or stroma, with proteolytic enzymes

Ex: Metalloproteinases: attack the basement membrane

Ex: Serine proteinases and cystine proteinases: attack extracellular matrix proteins 

the extent to which the malignant cells resemble their mature counterparts

- the less the malignancy is identifiable in comparision to a mature prototype, the more "undifferentiated" it is

-the "grade of malignancy" is based on it's degree of differentiation. A well differentiated tumor is "low-grade", a poorly differentiated tumor is "high-grade"

- 

it's degree of differentiation

- a well-differentiated tumor is "low-grade"

- a poor-differentiated tumor is "high-grade" 

-a complete loss of differentiation of cells

-anaplastic cells vary widely in their size and morphologic appearance and bear no resemblance to their mature counterparts 

- the nuclei are larger than normal, and the ratio of the nucleus to the cytoplasm is increased (increased N:C ratio)

-there may be more than one nucleus

- the nucleus and/or the cell itself has irregular contours

-nuclei are dark

-nucleoli are prominent

-mitotic figures are increased 

-noncontiguous spread of malignancy

-ability to move in a noncontiguous fashion to lymph nodes or other organs 

1.invasion

2. intravasatuib

3. Intravascular circulation

4. Extravasation

5. Local growth in the metastic location

6. Angiogenesis 

- destruction of and movement through adjacent tissue

-invasion requires that the malignant cells be able to degrade the surrounding tissue, or stroma, with proteolytic enzymes

-metalloproteinases: attack the basement membrane

-serine proteinases and cystine proteinases: attack extracellular matrix proteins.

6 Steps of metastasis:

1. invasion

2. intravasation

3. Intravascular circulation

4. Extravasation

5. Local growth in the metastatic location

6. Angiogenesis 

 Describe the Intravasation step of metastasis.

-movement into lymphatic or blood vessels

-this requires the ability to destroy the capillary or lymphatic basement membrane and to bore holes through or between endothelial cells

-enzymes destroy basement membrane or endothelial cells

6 steps of metastasis:

1. Invasion

2. Intraversion

3. Intravascular circulation

4. Extravasation

5. Local growth in the metastatic location

6. Angiogenesis 

- circulating lymphocytes destroy most of the tumor cells that gain entry into the blood stream. Single cells are more likely to be eliminated than clusters of cells.

-clumps of tumor cells surrounded by platelets (tumor emboli) are more likely to survive in the blood stream

6 steps of metastasis:

1. invasion

2. intravasation

3. intravascular circulation

4. extravasation

5. local growth in the metastatic location

6. angiogenesis 

- movement out of the lymphatic vessels or blood vessels

-the flow of lymph or blood can carry tumor emboli to organs far removed from the site of the primary malignancy.

-extravasation can occur in lymph nodes, if the tumor emboli intravasated to lymphatics, or into the organs, if they were present in the blood steam

-matastasis most commonly occur in organs that receive a high volume of blood flow, such as the lungs or the liver

6 steps of metastasis:

1. invasion

2. intravasation

3. intravascular circulation

4. extravasation

5. local growth in the metastatic location

6. angiogenesis 

- the malignant cells must be able to avoid growth-inhibiting signals and mechanisms of the host tissue, such as protease inhibitors

6 steps of metastasis:

1. invasion

2. intravasation

3. intravascular circulation

4. extravasation

5. local growth in the metastatic location

6. angiogenesis 

- angiogenesis is the introduction of growth of new blood vessels.  Without a supply of oxygen, the metastatic tumor cannot grow.

6 steps of metastasis:

1. invasion

2. intravasation

3. intravascular circulation

4. extravasion

5. local growth in the metastatic location

6. angiogenesis 

Determined by assessing:

   - the extent of local growth

--size of the neoplasm

--extension to surrounding tissue

-lymph node metastases

--number of involved lymph nodes

--size of lymph node metastases

-distant organ metastases

**stage is correlated with survival

**stage determines treament 

1. Tertiary prevention: early detection, effective treament (most cancers are treated with a combination of surgery, radiotherapy and chemotherapy...these treatments can cause nausea, fatigue, abdominal pain, infections, hair loss)

-prostate: yearly PSA levels for men beginning at the age of 50

- Breast: screening mammorgraphies for women over 40

-Colorectal: yearly fecal occulut blood testing and colonoscopy every 5 years.

-lung: no effective screening tool

-cervix: PAP smear 

2. Secondary Prevention: risk factor management

- smoking is the leading cause of lung cancer

-health care giver advice to patients to stop smoking has declined over the last 2 decades

-colon cancer: linked to diets high in fat, low in vegetables, and to a sedentary lifestyle

-sex, age, family history

-Breast cancer: estrogen exposeure, high socioeconomic status

-Prostate cancer: dietary fat, smoking, african-american.

3. Primary Prevention: avoiding the development of risk factors to begin with 

any injury or disease producing physiological derangement in the body that results in the death of the individual

examples: gunshot to the head, drowning, drug overdose, etc.

actual hysiological derangement that is produced by he cause of death that results in death

Examples: hemorrhage, arrhythmia, asphyxia, etc.

Suicide

Homicide

Accident

Undetermined

Natural

death occurring under circumstances that neither the victim nor anyone else knowingly brought about and the resulting death was not reasonably foreseeable

victim dies of natural causes and no non-natural event caused or contriuted to the death

** this is most of what forensic pathologist's see

muzzle of the weapon is in contact with the target

muzzle imprint or muzzle stamp

- carcinoma=histogenesis is from epithelial cells which, for the most part, are cells that normally come in contact with the environment outside the body

muzzle of the weapon is not in contact but is close enough that unburned poder leaving the barrel with the bullet retains enough energy to cause microabrasions (stippling) of the skin

occurs from intermediate range gunshot wound

microabrasions

1. attachment

2. Degradation

3. migration 

actual alkaloid extracts of opium

morphoine and codeine

- the pathologic counterpart of ARDS

-non-specific pattern of pulmonary parencymal reaction to a variety of acute insults 

any medication inding to opioid receptors found in the brain or GI tract

endogenous(produced w/i the body):  endorphins, enkephalins

exogeneous (semisynthetic or fully synthetic): semi:heroin, oxycodone, hydrocodone. fully: methadone, fentanyl, propoxyphene

frothy fluid discharge from the mouth and nose caused from profound pulmonary edema

three settings this is seen in: opioid toxicity, drowning, head injuries

ethylene glycol

when injested it can result in severe toxicity and death

 toxic intermediates: oxylate, oxalic acid

vitreous humor

what is it? where is it collected from??

fluid collected from the posterior chamber of the eye. 

vitreous ethanol level lags the blood by 2 hours

most likely still drinking around the time of death

vitreous ethanol level is lower than the blood ethanol level

death while in the elimination phase

ethanol levels were falling during death and the individual had not ingested ethanol immediately prior to death

vitreous ethanol is higher than the blood ethanol level

200x greater affinity for hemoglobin than oxygen

50% saturation of hemoglobin by CO is enough to say that was the cause of death

this is helpful in determining whether someone in a fire died before, or during the fire.

still warm? short postmortem interval (have only been dead a few hours)

part of rigor mortis

1st 12 hours: rigor strenghtens with muscles becoming stiffer and stiffer

middle 12 hours: rigor remains fixed and firmly established (difficult to 'break')

3rd 12 hours: rigor passes, becoming less stiff

pooling of the blood

when you can't determine whether stiffness is 1st or 3rd 12hour, check this~~

bloodsettles in gravity dependent ares of the body due to stasis or lack of circulation.  The blood becomes 'fixed' and will not blanch

potasium levels can be measured (potassium is usually maintained by pumps, but after death it is able to leak into the extracellular matrix...vitreous fluid...so they will rise linearly after death)

glucose levels can also be evaluated (can check for diabetes as a cause of death) glucose levels should fall near to zero within several hours after death

desiccation (drying) of the skin and internal organs with reservation of structures.

arrid and dry environments

classic example of fibrotic interstitial lung disease

typically presents with: progressive dyspna and dry cough

clinically: exertional dyspnea, restrictive defect (low TLC), hypoxemia on exercise and tachypnea

Stages of idiopathic pulmonary fibrosis

Usual interstitial pneumonia (UIP) aleolar walls are thickened with extensive fibrosis and extreme abnormalities in alveolar architecture

Desquamative interstitial pneumonia (DIP) milder type of the disease characterized by minimal fibrosis, alveolar inflammation and fullness of the alveoli with macrophages.  (type 2 pneumocytes have been desquamated)

The partial pressure of CO2 in the arterial blood

- it is determined by the relationship between CO2 production (VCO2) and elimination (i.e. alveolar ventilation)

if alveolar ventilation is increased, PaCO2 will decrease proportionately(provided that VCO2 remains stable) 

fever, sepsis

Medications (aspirin, progesterone, xanthines) 

Metabolic acidosis

Maximum exercise

Hypoxemia

Anxiety 

What's the defintion of hypoxemia?

Also, there are several mechanisms of hypoxemia, what are they? 

Reduction of arterial P02

hypoventilation

low ventilation/perfusion (V/Q)

right-to-left shunt 

Resistence- the airflow through extrathoracic and intrathoracic airways

Elastance - opposing stretching the lung and thorax. 

emphysematous lungs are larger and more compliant

fibrotic lungs are smaller and less compliant (elastic recoil is greater) 

it's the measure of how much you force out after a forced inspiration in one second, over the total amount you can force out. 

If you have a reduced FEV1/FVC, that's the hallmark of obstructive defect 

extensive allergic alveolitis

pulmonary inflammation secondary to immune reaction to inhaled organic dusts

acute: occurs a few hours after exposure to an antigen. 

chronic: slowly progressive, the lung reveals inflammation with multinucleated giant cells forming scattered "loose" granulomas.

group of interstitial pulmonary diseases caused by inhalation of inorganic dusts.

Examples:

Siliocosis, asbestosis

an example of pneumonoconioses

it is caused by the inhalation of silicon dioxide (silica) which occurs in mining, sand blasting, and foundries

inhilation causes pulmonary inflammation and fibrosis.

a pneumoconioses

fibrotic pulmonary disease secondary to inhalation of asbestos fibers which occurred in mining, insulation, tile production, and ship building.

inhaled asbestos fibers deposit in the distal airway and alveoli are injested by macrophages.

large fibers penetrate into the interstitial space and become coted w/ iron rich protein and are called the asbestos bodies.

pleural plaques, pleural effusion and mesothelioma

also associated with increased risk for bronchogenic carcinoma

lethal cancer in the pleural space

no effective therapy

Lung cancer is classified into: (4)

1. squamous cell carcinoma

2. adenocarcinoma

3. large cell carcinoma

4. small cell carcinoma

small cell carcinoma

what is it?

what therapy?

highly malignant cancer, a majority of patients have metastatic disease at the time of diagnosis

chemotherapy

starts off as being more localize and mestasizes over time.

surgical resection