It breaks down by internucleosomal (between the nucleosome.)
What is the tissue reaction like during apoptosis?
No inflammation phagocytosis of ABs
Give an example of a pathologic pathway that could lead to apoptosis?
Injurious stimuli like radiation or hypoxia.
What will Apoptosis look like when in agarose gel culture cells?
It will look like a ladder pattern of DNA fragment.
What will necrosis or coag. Necrosis look like when in agarose gel culture cells?
It will look like diffuse smearing of DNA.
What is the receptor and the ligand that will signal apoptosis?
Ligand- FAS. Receptor- TNF
When a cell undergoes apoptosis what will leak out of the mitochondria?
When apoptotic cells breakdown they break down into what?
What happens to apoptotic bodies and how?
They are phagocytosed and they have ligands on them for phagocytic receptors.
What wil execution caspases do?
Once a cell is told to undergo apoptosis from: injury, withdrawal from growth factors, ligand FAS and receptor TNF, or cytotoxic T cells then the execution caspases start the degradation of cytoskeleton and nuclear proteins.
The FAS ligand brings what together in close proximity?
Several FAS death domains.
With several FAS death domains in proximity what happens?
Autocatalysis of caspase and this leads to apoptosis.
Where is the brain of a cell?
What are 2 catagories of intracellular accumulations?
1. Exogenous material. 2. Endogenous metabolites.
What is hemosiderin?
An endogenous metabolite that is an accumulation of iron from RBC.
What is anthracosis?
Accumulation of a pigment that blackens the lings and the involved lymph nodes.
Give 2 examples of endogenous metabolites without using hemosiderin?
1. Lipids. 2. Pigment from tattoos.
What is steatosis?
Abnormal accumulation of triglycerides in parenchynmal cells also it is a fatty change.
Where will steatosis usually happen at?
The liver, but can happen in the heart, muscles, and kidneys.
Steatosis can be caused by what?
Alcohol abuse, toxins, protein malnutrition, Diaetes M., Obesity, and anorexia.
What will alcohol dehydrogenase do with alcohols?
It converts them into aldehydes or ketones.
What will alcohol dehydrogenase do with methanol and ethylene glycol?
Methanol- converts it to formaldehyde. Ethylene glycol- converts it to oxalic acid.
Under a microscope what will intracellular accumulations of Cholesterol and cholesterol esters look like?
What is an intracellular accumulation of cholesterol and cholesterol esters in arteries called?
What are xanthomas?
Intracellular accumulations of cholesterol in the skin and tendon masses.
What are reabsorption droplets?
Intracellular accumulations of protein in proximal renal tubles.
What are russell bodies?
excess secretory protein synthesis which leads to intracellular accumulations of protein that leads to a distended ER with large eosinophilic inculsions.
What is amyloidosis?
Aggregation of abnormal proteins.
What are some neuro diagnosis of Intracellular accumulations of protein?
Alzheimer's, Huntington's, parkinsons's, Maybe Diabetes M. Type II.
What will help protect agains intracellular accumulations of proteins?
What is the pattern of hyaline cartilage intracellular accumulation?
There is no specific pattern of accumulation due to the variety of alteration.
What will hyaline cartilage accumulations look like in a microscope?
Homogenous GLASSY pink appearance.
What are some examples of intracelluar hyaline accumulations?
Where will intracellular accumulations of glycogen be found at?
In clear vacoules within the cytoplasm.
What causes intracellular accumulations of glycogen?
Glucose metabolism disorders like Diabetes M., and Genetic disorders that lead to glycogen storage disease.
Glycogen accumulations have Numbers like GSD type I-V and these are associated with an enzyme deficiency and a type of disease for the next five questions give the enzyme deficiency and type of disease for the numbers given.
GSD Type I?
Glucose-6-phosphatase, Von gierke's disease.
GSD Type II?
acid maltase, Pompe's disease.
GSD Type III?
Glycogen debrancher, cori's disease or Forbe's disease
GSD Type IV?
Glycogen branching enzyme, Andersen disease.
GSD Type V?
Muscle glycogen phosphorylase, McArdle disease.
What is Lipofuscin?
An endogenous intracellular accumulation of a brown pigment.
What is melanin?
A black pigment.
Hemosiderin is what?
A accumulation of Iron from RBC and it is considered an endogenous intracellular accumulation of a golden-brown pigment.
What does dystrophic mean?
Bad growth or abnormal growth.
What is dystrophic calcification?
Abnormal growth of calcium.
Dystrophic calcification deposition occurs where?
Only locally in dying tissue.
Dystrophic calcifications happens under what serum levels of calcium?
Under normal serum calcium levels.
What calcium metabolsim pathology is present with dystrophic calcification?
Dystrophic calcification effects arteries and hearts how?
Besides pulling Ca2+ out of the body what else will EDTA pull out of the body?
Metastatic calcifcation deposits calcium where?
IN otherwise normal tissues.
What is blood serum like during metastatic calcification?
The Calcium levels in serum are high it is also high in tissues.
Metastatic calcification is usually due to what?
What is the most common cause of hypercalcemia?
What are the 4 pricipal causes of metastatic calcification?
1. Increased PTH from a primary tumor on the parathyroid glands. 2. Bone destruction. 3. Vitamin D related. 4. Renal failure leading to increased phosphate retention leading to secondary hyperparathyroidism.
Interstitial tissue of the vasculature, kidneys, lungs, gastric mucosa.
What is a pathologic calcification?
What is multiple myeloma?
Widespread lucencies in the bone.
Increased PTH leads to what?
Increased serum calcium.
Increased Calcitonin leads to what?
decreased serum calcium and increased bone calcium.
What is inflammation?
Reaction of blood vessels leading to accumulation of fluid and leukocytes in the extravascular tissues.
What 3 thing will inflammation do?
1. Eliminate microbes and toxins. 2. Eliminate necrotic cells and tissues. 3. prepare for tissue repair.
What are the components of acute and chronic inflammatory responses?
Circulating cells, portiens, blood vessel cells, and proteins of extracellualr matrix.
With inflammation what is the major WBC?
With inflammation there are how many more neutrophils than lymphocytes?
there are 2 neutrophils for every lymphocyte.
Neutrophil does what with inflammation and turns into what?
It is the first responder that works on bacterial or fungal infections and deaths turns them into pus.
A lymphocyte becomes what in tissue?
Lymphocytes work during what?
Monocytes do what are? What are they called in tissues?
They present pathogens parts to T cells, and they are called macrophages in tissue.
Eosinophils do what?
They work with parasite and allergic responses.
Basophils are what in tissues?
Basophils do what?
releasing histamines in response to allergic and antigen responses.
What is the Lifespan of a RBC?
What is the lifespan of a WBC?
Days to years.
What is the lifespan of platelets?
With acute inflammation what is the main WBC?
Which one is faster onset chronic or acute inflammation?
Which one lasts longer chronic or acute inflammation?
With chronic inflammation what is the main WBC?
macrohpages and lymphocytes.
What are the 5 signs and symptoms of acute inflammation?
1. Redness. 2. Heat. 3. Swelling. 4. Pain. 5. Loss of function.
With acute inflammation what happens to blood flow?
Vascular dilation and increased blood flow.
What is edema like with acute inflammation?
deposition of plasma fluid and proteins.
What will accumulate at the injury site of an acute inflammation?
Normal arteriol blood pressure is 32 mmHg what will it be during acute inflammation?
50 mm Hg.
The normal venous blood pressure is 25 mm Hg what will it be during acute inflammation?
30 mm Hg.
What is the net result of fluid flow with acute inflammation?
Net is an excess of extravasated fluid.
What is oncotic pressure?
Pulling in because concentration of proteins is higher in vasculature.
What is Rouleaux?
Stacking of RBC.
What is margination?
RBC go to center and White blood cells go to margins.
What is pavementing?
Rolling, tight binding, diapedisis
What will TNF and IL-1 do?
They are adhesion molecules for leukocytes.
Leukocytes can phagocytosis particles as they bind to what surface binding proteins?
Production of microbicidal reactive oxygen intermediates happens where?
Within phagocytic vesicles.
What are the 2 major mediators of inflammation?
Plasma derived and cell derived.
Histamine is released from what 2 cells?
Platelets and mast cells.
What is the action of histamine?
Stimulates retraction of endothelial cells of the venules which increases gaps and increases permeability.
How long will histamine action last and why?
Short action because it is inactivated by histaminase.
What Vitamin can stabilize Mast cells?
Vitamin C 2-3 grams.
What is bradykinin?
A hormone that causes inflammation.
Bradykinin has a similar action as what?
Bradykinin induces what?
Name the liver (the other would be cellular) derived chemical mediators of inflammation?
kinin system which is bradykinin, coagulation/ fibrionlysis system, anaphylatoxins, membrane attack complex.
The complement system is a group of what?
plasma proteins produced by the liver that circulate in an inactive form.
How is the complement system activated?
Through classical or alternative pathways.
Activation of the complement system leads to what?
formation of biologically active fragments, intermediate complexes, and terminal membrane attack complexes.
What are the 4 main functions of the activated complement derivatives?
1. Opsonization- facilitated phagocytosis of bacteria. 2. Anaphylaxis- histamine release with increased vessel wall permeability. 3. Chemotaxis- migration of leukocytes. 4. Cell lysis- through the action of MAC.
Activation of the complement system by different pathways leads to cleavage of what?
The functions of the complement system are mediated by breakdown of what?
C3 and other complement proteins, and by membrane attack complex.
What is the first step of the complement system?
What is the second step of the complement system?
Attachment of the opsonized bacterium to the PMN.
What is the third step of the complement system?
Formation of phagocytic vacuole.
What will cleave C3?
What is the classical complement pathway aka?
Mannose-binding lectin (MBL).
The classical and alternative complement pathways converge into what?
What happens to C3 when it is cleaved?
it becomes Ca and then Cb.
Factor XII is aka?
The 4 plasma mediator systems are triggered by what?
Activation of factor XII aka hageman factor.
Thrombin induces inflammation how?
By binding to protease-activated receptors on platelets, endothelium, smooth muscle, and other cells.
Arachidonic acid is derived from what?
Phospholipids through the action of phospholipases.
What 2 pathways is arachidonic acid metabolized into?
1. Lipoxygenase. 2. Cyclooxygenase.
The cyclooxygenase is aka?
What is leukotrienes?
an arachidonic acid derivative that does chemotaxis, vascular permeability, bronchospasm.
What is lipoxins?
an arachidonic acid derivative that does vasodilation, inhibition of neutrophil chemotaxis, monocyte adhesion.
What is thromboxane?
An arachidonic acid derivative that does platelet aggregation, thrombosis.
What is prostacyclin?
An arachidonic acid derivative that opposes the effects of thromboxane.
What is prostaglandins?
An arachidonic acid derivative that does smooth muscle contraction.
What type of oil is good for conversion to arachidonic acid?
What type of oil is not good for conversion to arachidonic acid, but good for omega 3?
In general arachidonic acid derivatives do what?
TNF and IL-1 will do what during acute inflammation?
Collagen, proteoglycans, and adhesive glycoproteins.
What vitamin is needed for HO-ization?
What is fibronectin?
2 glycoprotein chains held by disulfide bonds.
What binds ECM components and interacts with the cytoskeleton at focal adhesions complexes?
Angiogenesis by mobilizatin of ____ from the bone marrow.
EPC's from the bone marrow migrate to where?
Site of injury or tumor growth.
What do EPC's do at sights of injury?
They differentiate and form a mature network of vessels.
What are MMP's?
Matrix metalloproteinase. They help degrade collagen and other ECM proteins.
MMP's are dependent on what?
What are the 4 mechanisms of MMP regulation?
1. regulation of synthesis by growth factors or cytokines. 2. Inhibition of synthsis by corticosteroids or TGF-beta. 3. secreted in inactive form. 4. Blockage of the enzymes by specific tissue inhibitors of metalloproteinase.
The inflammation phase of wound healing lasts how long?
The granulation tissue phase of the healing process takes place when?
0.3 days until 10 days.
The wound contraction phase of the healing process takes place when?
3 days to 30 days.
What will clean up an injured site after the healing process?
What type of scaring occurs with primary and secondary and tertiary intention healing?
Primary- minimal scarring. Secondary- broader scar. Tertiary- wound is purposely left open.
What type of injury is primary intention healing?
Little tissue loss.
Most surgical wounds heal by which intention?
Primary inention healing.
A primary intention wound is closed how?
By sutures, staples or adhesive.
What is allowed to happen to the wound with secondary intention healing?
It is allowed to granulate.
Why can the healing process be slower with secondary intention healing?
Due to the presence of drainage from infection surgeons may pack the wound with gauze or use a drainage system.
How long will a tertiary intention scar be left open?
What is Keloid?
Excess collagen deposition in the skin forming a raised scar.
Stimulus from chronic inflammation activates what?
Macrophages and lymphocytes.
Activated macrohages and lymphocytes in chronic inflammation areas lead to what?
Production of growth factors, cytokines.
Growth factors cytokines in a chronic inflammation lead to what?
Increased collagen synthesis.
Increased collagen synthesis in a chronic inflammation leads to what?
Activated macrohages and lymphocytes in chronic inflammation do what to MMP's?
They decrease their activity.
What happens in chronic inflammation when MMP's decrease their activities?
IT will decrease the collagen degradation.
When collagen is not degraded or is allowed to be synthesised in chronic inflammation what happens?
What happens with an injury when the stimulus that caused the acute injury is removed?
Parenchymal cell death.
Parenchymal cell death with superficial wounds leads to what?
Regeneration- restitution of normal structure.
Parenchymal cell death with deep wounds leads to what?
Healing- scar formation organizatin of exudate.
What is neoplasia?
What is a tumor?
Formation of masses.
What is Cancer?
tissue invasion appearance like crawling crab.
What is oncology?
The branch of science dealing with neoplasia.
Will a tumor always be a neoplasia?
Is a neoplasia always a tumor?
What is hyperplasia?
Increase in number of cells.
What is metaplasia?
1 adult cell type is replaced by another.
What is dysplasia?
abnormal growth with loss of cellular orientation, shape.
What is anaplasia?
An IRREVERSIBLE abnormal cell lacking differentiation.
What is irreversible neoplasia?
a clonal proliferation of cells that is uncontrolled and excessive.
What is desmoplasia?
REVERSIBLE fibrous tissue formation in response to neoplasm.
What are the 2 clinical classifications of tumors and what are they like?
1. Benign- good. 2. Malignant- BAD.
What is the name of a slow and a fast growing tumor?
slow- bening. Fast- malignant.
Which type of tumor has metastases (transfer to other parts of the body)?
What is the external surface of benign and malignant tumors?
Benign- smooth, malignant- irregular.
What type of tumor will have a capsule?
What type of tumor will show necrosis?
What type of tumor will have hemorrhage?
Tumors can get up to how big before they need a new blood supply?
How will large tumors get new blood supply?
They release chemotaxic factors that induce angiogenesis.
What will the benign and malignant tumors look like microscopically?
Benign- look like normal tissue of origin. Malignant- does not resemble normal tissue of origin.
What will benign and malignant tumor cells look like microscopically?
Benign- well differentiated. Malignant- poorly differentiated.
What will benign and malignant tumor cell nuclei look like microscopically?
Benign- normal size and shape also uniform. Malignant- variable shape (Pleomorphic).
What will tumor cells mitoses be like for benign and malignant tumors?
Benign- few. Malignant- Many and irregular.
How many normal chromosomes do we have?
what do we look for in a vaginal smear?
Nuclear to cytoplasmic ratio.
What does metastasis mean?
What are the 4 main pathways of metastasis?
1. Lymphatics. 2. Blood. 3. Seeding surface of body cavity (transcoelomic spread). 4. Intraepitheilal.
What is the first step in the metastatic cascade?
a primary tumor.
What is the second step in the metastatic cascade?
Metastatic clone evolves.
What is the third step in the metastatic cascade?
Proliferation of the clone and invasion of vessel.
What is the 4th step in the metastatic cascade?
Transport by circulation.
What is the 5th step in the metastatic cascade?
Emboilization (getting caught).
Where wil emboilization most commoly take place?
At areas where vasculature gets funneled.
What is the 6th step in the metastatic cascade?
What is the 7th step in the metastatic cascade?
New tumor formation at the site of metastasis.
What is a clone?
A distinct subpopulation.
What is the biological role of tumor-induced angiogenesis?
TO overcome limitations of nutrient and oxygen delivery.
Seeding surfaces of body cavities is a direct seeding and what is the problem?
There is no plain of resistance to spreading.
What is mesenchyme?
cells of mesodermal origin that are capable of developing into connective tissues, blood, and lymphatic and blood vessels.
Mesenchymal tumors are named how (both benign and malignant?
Benign- use cell of origin + oma. Malignant- cell of origin + sarcoma
Epithelial tumors are named how (both benign and malignant?
Benign- use terms like adenoma and papilloma. Malignant- use terms like carcinoma.
Carcinoma implies what?
Epithelial origin but malignant
Sarcoma implies what?
It is of mesenchymal origin but malignant.
What would a benign and malignant tumor of fibroblast cells be called?
B- Fibroma. M- Fibrosarcoma.
What would a benign and malignant tumor of fat cells be called?
B- Lipoma M- Liposarcoma.
What would a benign and malignant tumor of blood vessels?
B- hemangioma. M- Hemangiosarcoma.
What would a benign and malignant tumor of smooth muscle cells?
B- Leiomyoma. M- Leiomyosarcoma.
What would a benign and malignant tumor of striated muscle be called?
B- rhadbomyoma. M- Rhabdomyosarcoma.
What would a benign and malignant tumor of cartilage cells be called?
B- Chondroma. M- Condrosacroma.
What would a benign and malignant tumor of squamous skin cells be called?
B- Epithelioma. M- Squamouse cell carcinoma.
What would a benign and malignant tumor of transitional epithelium be called?
A parasite that acts as a urinary bladder carcinogen.
What is opisthorchis sinesis?
A chinese live fluke that acts as a bile duct and liver carcinogen.
How can a virus cause cancer in DNA?
It integrates in the DNA.
Speaking of viral carcinogens what is transduction?
acute transforming RNA viruses in the form of cellular oncogenes.
Speaking of viral carcinogens what is insertion?
Slow transforming oncogenic RNA viruses; insert into the genome and activate a latent cellular oncogene, which is then capable of transforming the normal cell into a malignant cell.
Human papilloma virus aka HPV is what and what are the 2 types?
Invasive cervical carcinoma types 16, 18.
Epstein-Barr virus can be what type of carcinogen?
Burkett's lymphoma, nasopharangeal.
Hepatitis B and C viruses are what type of carcinogen?
Kaposi's sarcoma is associated with what?
What type of carcinogen is kapsoi's sarcoma?
What are RNA viruses that are carcinogenic?
Human T-cell leukemia/lymphoma virus (HTLV-1), Adult T cell leukemia which is in HIV group.
What are the 2 types of human oncogenes?
viral and cellular.
What is an oncogene?
A gene that is the cause of cancer.
An oncogene has gained what?
function and becomes a cancer-inducing agent.
How many alleles need to be damaged for a gene to become an oncogene?
A proto-oncogene transformes into an oncogene by going through what 4 steps?
1. point mutation. 2. Gene amplification. 3. Chromosomal rearrangement. 4. Insertion of viral oncogene.
How will the MYC oncogene be activated in Burkitt's lymphoma?
8 switches with 14.
What gene is associated with CML?
What gene is associated with burkitt's lymphoma?
What gene is associated with follicular and undifferentiated lymphomas?
What gene is associated with breast, ovarian, and gastric carcinomas?
What gene is associated with colon cancer?
What gene is associated with a lung tumor?
What gene is associated with neuroblastoma?
What gene is associated with herebitary papullary renal cancer?
What gene is associated with multiple endocrine neoplasia (MEN) types II and III?
What gene is associated with GI stomal tumor?
What do tumor suppressor genes do?
They protect genes against activated or newly acquired oncogenes.
What happens when a tumor suppressor gene has lost function?
it is no longer a cancer-inhibiting agent.
With tumor suppressor genes how many allels must be lost for expression of disease?
Name 2 of the best tumor suppressor genes?
p53, retinoblastoma gene (rb-1).
Retinoblastoma gene protects against what?
p53 protets against what type of tumor?
Numerous like brest and colon.
What type of tumor suppressor genes protect neurofibromatosis 1 and 2?
NF-1 and NF-2.
Wilms tumor (kidney) is protected by what tumor suppressor gene?
Familial adenomatous polyposis coli (intestine) is protected by what tumor suppressor gene?
Breast carcinoma and ovarian carcinoma is protected by what tumor suppressor gene?
Breast carcinoma is protected by what tumor suppressor gene?
Melanoma is protected by what tumor suppressor gene?
pancreatic cancer is protected by what tumor suppressor gene?
Colon cancer is protected by what tumor suppressor gene?
What is the generic way of naming Tumor suppressor genes?
D___ C. stands for deleted __name of area___ cancer
Name 5 types of hereditary cancers?
1. Neurofibromatosis type I. 2. Familial adenomatous polyposis coli. 3. Wilms tumor. 4. skin tumors in xeroderma pigmentosum. 5. Chromosomal fragility syndromes.
TNF does what?
Activates white blood cells.
Some cancers do what under the influence of immune factors?
What is used for treatment of bladder cancer?
Tumor vaccines are used for treatment of what type of carcinomas?
Melanoma and renal cells.
Tumor antigens may be used for what?
as tumor markers.
What should tumor markers be used for?
Not as primary diagnosis, but to confirm a diagnosis and to monitor therapy.
What is the tumor marker used to screen for prostate carcinoma?
What is the tumor marker used to screen for pancreatic cancer?
What is the tumor marker used to screen for testies?
What is the tumor marker used to screen for moles, and gestational trophoblastic tumors?
What is the tumor marker used to screen for ovarian, and malignant epithelial tumors?
What is the tumor marker used to screen for melanoma, neural tumors, and astrocytomas?
What is the tumor marker used to screen for metastases to bone?
What is the tumor marker used to screen for neuroblastoma, lung, and gastric cancer?
What is the tumor marker used to screen for hairy cell leukemia?
What is the tumor marker used to screen for pancreatic adenocarcinoma?
What is the tumor marker used to screen for thyroid cancers?
Leukemias and lymphomas cause what type of paraneoplastic syndrome?
gout, urate nephropathy.
Hypercalcemia is a paraneoplastic syndrome caused by what types of cancers?
squamous cell carcinoma of the lung, breast, renal
A venous thrombosis is a paraneoplastic syndrome caused by what type of cancer?
What are the 7 warning signals of cancer?
CAUTION= Change on bowel or bladder cancer, A sore that doesn't heal, Unusual bleeding or discharge, Thickening or lump in breast or elsewhere, Indigestion or difficulty swallowing, Obvious change in wart or mole, Nagging cough or hoarseness.
Psammos means what?
How are psammoma bodies seen?
with a microscope.
Psammoma bodies are seen with several cancers and appear as what?
Laminated, concentricm calcific spherules.
psammoma bodies are though to arise from what?
infarction and calcification of papillae tips. And calcification of intralymphatic tumor thrombi.
Deaths from lung cancer is on the rise or fall for males and females.
Plateaued in males and is rising for females.
What is the first and second leading cause of death in the USA?
1. Heart disease. 2. Cancer.
What is incidence?
The number of new cases at a defined time.
What is prevalence?
All cases new and old at a defined time.
What is mortality?
Deaths attributed to something.
What is the most common sign of colon cancer?
Blood in stool
What is the most important risk factor for colon cancer?
What is the most important risk factor for breast cancer?
What is the most common sign of cervix cancer?
What is the most important risk factor with cervix cancer?
What is the most common sign of uterus cancer and what is the most important risk factor?
Vaginal bleeding, and hormonal imbalance.
What is the most common sign of skin cancer and what is the most important risk factor?
Skin lesion, sun expsoure.
What cancer has the most incidence ( New cases) amoung Males and Females?