Path Final Additional cards Flashcards
What is hypertrophy?
1) General increase in the bulk, not due to tumor formation2) increase in size of cells not #
What happens to tissue once it stretches or stress is put on a tissue?
It will adapt to the stress
What is atrophy or hypotrophy?
wasting of tissue from death and reabsorption of cells, diminished cellular proliferation, decreased cellular volume, pressure, ischemia or malnutrition that leads to lessened function or hormonal changes
What causes atrophy in the brain?
Aging and reduced blood supply
How does a brain that has undergone atrophy appear grossly?
The brain has narrowed gyri and widened sulci
What causes atrophy of the thyroid gland?
Longstanding autoimmune disease
What is hyperplasia?
increase in # cells excluding tumor formation
What causes endometrial hyperplasia?
Estrogen.
What causes calluses on the heels of feet?
Stresses due to constant wear on feet (ie: tight shoes)
What is BPH?
Benigh Prostatic hyperplasia
What is hypoplasia?
incomplete development of tissue (ie: neural fold defects)
What is metaplasia?
reversible replacement of one differentiated cell type with another differentiated cell type (ie: barrett’s esophagus where cells have migrated from the stomach to the esophagus due to constant stress)
What is anaplasia?
A change in the structure of cells and a change in their orientation to each other.
What is aplasia?
The defective development, or congenital absence of an organ or tissue
What is dysplasia?
Abnormal tissue growth with loss of cell orientation, shape, and size
What is dysplasia?
Abnormal tissue growth with loss of cell orientation, shape, and size
Dysplasia is always what?
Pre-cancerous
What type of cell injury is found with lysosome swelling and rupture?
Irreversible as necrosis will occur
What cell injury occurs when fat calcification begins?
Irreversible
What happens to reversible damaged cells when looking at them with light microscope?
They have fatty changes (steatosis).
Is nuclear clumping the same as nuclear condensation?
NO!
What is the difference between necrosis and apoptosis?
Necrosis- common after ischemia and chemical injury CELL SWELLING. Apoptosis- is programmed cell death and CELL SHRINKAGE.
Does necrosis or apoptosis has neighbor or adjacent cell inflammation?
Usually necrosis
What happens to the plasma membrane during necrosis?
It is disrupted
What happens to the plasma membrane during apoptosis?
Intact/altered.
What happens with the cells contents with necrosis ?
enzymatically digested
What happens with the cells contents with apoptosis?
intact and packaged to be phagocytosed
What causes necrosis?
Inavriably pathologic
What causes apoptosis?
Often physiological
What does serum CK-MB check for?
Cardiac tissue ischemia
What does serum CK-BB check for?
Brain Tissue ischemia
What does serum CK-MM check for?
Generic muscle ischemia
What does cytochrome c do once it is outside of the mitochondrial membrane?
It induces secondary apoptotic effects
What are the sources of internal calcium?
1) mitochondrial damage2) cell injury (external calcium enters cell)3) ER damage
Where will Vitamin E be doing free radical protection?
In the membranes.
Glutothione is stored mostly where and to do what?
Stored in the retina to protect against all redox reactions.
What is the role of P-450?
Detox. It is enzymes that increase the solubility of compounds and help excrete them.
What is the down side of P-450?
While detoxing it can make some reactive oxygen intermediates which can injure cells.
Where are the P-450 enzymes found?
In the Smooth ER of hepatocytes.
What process is NADPH oxidase found in?
Pentose Shunt
Is iron required in the human body?
yes but excess can cause oxidative changes
Is copper required in the human body?
Yes but only in trace amounts
Free radical injury is induced through what?
membrane lipid peroxidation, protein modification, DNA breakage.
How are free radicals degraded?
Through enzymes, spontaneous decay, and antioxidants.
Why is homogenated milk bad for us?
Xanthine oxidase is better absorbed in body and causes more free radicals in circulation
Reperfusion after anoxia (an abnormally low amount of oxygen in the body tissues) induces what?
Free radical production.
What are some free radicals found in the body?
Super oxide, peroxide, hydroxide and nitrous oxide
What are some antioxidants that neutralize the free radicals in the body that are found in the cytosol?
Superoxide dismutaseGlutathionePeroxidaseFerritinCeruloplasminQuercitin
What is the function of ferritin?
Moves iron around the body
What is the function of ceruloplasmin
Transports copper around the body
Where is quercitin found?
in orange peel (white part)
What can initiate injury via free radicals?
Radiation exposure, metabolism of drugs (phase I), redox reaction, nitric oxide, transition metals, leukocyte oxidative burst
How do free radicals cause cell injury?
Through membrane lipid peroxidation, protein modification and DNA breakage
What are the different types of necrosis?
1) Coagulative2) Liquefactive3) Caseous4) Fat5) Fibrinoid6) Gangrenous
Coagulative necrosis happens with necrosis to what areas?
Heart, liver, and kidney.
Coagulative necrosis is a result of what?
Protein denaturation.
What will coagulative necrosis look like?
Preservation of basic cell outline for several days.
Liquefactive necrosis happens where?
Brain
Liquefactive necrosis is characteristic of what 2 things?
- Bacterial infection. 2. CNS stroke.
Liquefactive necrosis is a result of what?
Enzymatic digestion.
Gangrenous necrosis is associated with what area?
Limbs and GI tract.
Gangrenous necrosis usually results in what?
limb with loss of blood and Coagulation necrosis.
What is wet gangrene?
Coagulation necrosis with liquifactive action of bacterial infection and attracted leukocytes.
Caseous necrosis occurs due to what?
It is seen in tuberculosis infections.
What is the appearance of caseous necrosis?
Cheesy white appearance.
Caseous necrosis is a distinct form of which type of necrosis?
Coagulative necrosis
What is makes caseous necrosis a special form of coagulative necrosis?
Tissue architecture is obliterated unlike coagulative necrosis
How does Caseous necrosis look microscopically?
1) amorphus granular debris of fragmented coagulated cell2) amorphus granular debris enclosed within distinctive inflammatory border (granulmatous reaction)
Can scarring from caseous necrosis be seen via x-ray? And how long does scarring last?
Yes it can be seen in x-ray and the scarring remains with the patient for life
Fat necrosis occurs where?
In the pancreas
Is fat necrosis a typical necrosis pattern?
No
What will fat necrosis look like under microscope?
Foci of shadowy outlines of fat cells with basophilic calcium deposits surrounded by inflammatory reaction.
What will fat necrosis look like grossly?
Chalky area due to fat saponification
Is fat necrosis focal or widespread?
Focal area of fat destruction usually due to lipase release
What does P-450 do? What is an unfortunate result?
P-450 neutralizes toxins but creates free radicals
What is the stimulus for coagulative necrosis?
Hypoxia, toxins
What is the stimulus for apoptosis?
Physiologic and pathologic
What is the histology of the coagulative necrosis?
Cellular swellingcoagulative necrosisorganelle disruption
What is the histology for apoptosis?
Cellular shrinkageChromatin condensationApoptotic bodies
What is the DNA Breakdown in coagulative necrosis?
Random, diffuse
What is the DNA Breakdown in apoptosis?
Internucleosomal
What are the mechanisms of coagulative necrosis?
ATP depletionMembrane injuryFree radical damage
What are the mechanisms of apoptosis?
Gene activationEndonucleasesProteases
What is the tissue reaction of coagulative necrosis?
Inflammation
What is the tissue reaction of apoptosis?
No inflammationPhagocytosis of ABs
During what instances does apoptosis occur?
1) Embryogenesis2) hormone induction (menstruation)3) immune cell-mediated death4) injurious stimuli (ie: radiation, hypoxia)5) regulation of cell population and tumor suppression6) atrophy (ie: endometrial lining during menopause)
Which type of cell death is more controlled?
Apoptosis
Which type of cell death involves more cells?
Necrosis
What are the two types of pathologic calcification?
Dystrophic calcificationMetastatic calcification
Where does Dystrophic calcification occur?
Deposition occurring locally in dying tissue
What happens to the serum calcium level of the dystrophic calcification?
Nothing, it is normal serum calcium level
Is there any calcium metabolism pathology associated with dystrophic calcification?
No, no calcium metabolism pathology
What are some examples of dystrophic calcification?
Atherosclerosis of arteries, damaged heart valves
Where does metastatic calcification occur?
Deposition in otherwise normal tissue
What happens to the serum calcium level of the metabolic calcification?
Systemic elevation calcium levels in the blood and all tissues
What usually causes metastatic calcification?
Usually due to secondary hypercalcemia
What happens to calcium levels in injured cells with dystrophic calcification?
The calcium levels will increase due to release from ER and mitochondria
What happens to mitochondrial initiation with dystrophic calcification?
The mitochondrial permeability transition increases and therefore calcium diffuses through into the cell.
What is arachidonic acid?
Arachidonic acid is derived from phospholipids through the action of phospholipases
How is arachidonic acid metabolized?
1) Lipoxygenase pathway2) Cyclooxygenase pathway
What are the 5 arachidonic acid derivatives?
1) Leukotrienes2) Lipoxins3) Thromboxane4) Prostacyclin5) Prostaglandins
What is the function of leukotrienes?
Chemoxtaxis, vascular permeability and bronchospasm
What is the function of lipoxins?
vasodilatation, inhibition of neutrophil chemotaxis, and monocyte adhesion
What is the function of thromboxane?
Platelet aggregation, thrombosis
What is the function of Prostacyclin?
Opposes the effects of thromboxane
What is the function of Prostaglandins?
Smooth muscle contraction
Is Omega 3 fatty acids (fish oil) a good substrate for conversion?
No it is a poor substrate
Are animal fats good for conversion to substrate?
Yes, animal fat is a good substrate
Generally, what lymphokines are released with macrophage activation and lead to inflammation?
Interleukin-1 and Tumor Necrosis factor
What are the acute-phase reactions activated by interleukin-1 and tumor necrosis factor?
1) Fever2) increased sleep need3) decreased appetite4) Increased acute-phase proteins5) hemodynamic effects (shock)6) Neutrophilia (attract neutrophils)
What are the endothelial effects activated by interleukin-1 and tumor necrosis factor?
1) increased leukocyte adherence2) Increased prostacyclin synthesis3) Increased procoagulant activity4) decreased anticoagulant activity5) Increased Interleukin and platelet derived growth factor
What are the fibroblast effects activated by interleukin-1 and tumor necrosis factor?
1) increased proliferation2) increased collagen synthesis3) increased collagenase4) increased protease5) increased prostaglandin synthesis
What are the leukocyte effects activated by interleukin-1 and tumor necrosis factor?
Increased cytokine secretion (interleukin 6 and 8)
What does long term tumor necrotic factor production lead to?
Cachexia (wasting away syndrome)
What leads to the pathogenesis of fever?
TNF and IL-1 that changes the set point of internal temperature in the hypothalamus
What are two types of edema?
Exudate and Transudate
What is exudate made of?
It is rich in protein and blood cells and are typical of inflammation
What is transudate made of?
- Contains less protein and fewer cells
- an ultra-filtrate of plasma fluid
What is a typical cause of transudate?
Typical of hydrostatic or osmotic pressure pathology
What is the specific gravity of transudate?
Specific gravity is usually less than 1.012 and a protein content of less than 2gm/100mL
What are some factors towards the pathogenesis of Edema?
1) increase in hydrostatic pressure2) Increase in wall permeability3) Decrease oncotic pressure (decrease albumin concentration)4) Lymphatic obstruction
Is transudate hypocellular or cellular?
Hypocellular
Is transudate protein rich or poor?
Protein poor
What is the specific gravity of transudate?
Specific gravity <1.012
What is transudate due to?
Increased hydrostatic pressureDecreased Oncotic pressureNa+ retention
Is exudate hypocellular or cellular?
Cellular
Is exudate protein rich or poor?
Protein rich
What is the specific gravity of exudate?
Specific gravity >1.020
What is exudate due to?
Lymphatic obstruction or Inflammation
What are the 4 mechanisms of MMP regulation?
- 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?
3 days.
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?
Macrophages.
What type of scaring occurs with primary intention healing?
Minimal scarring
What type of scaring occurs with secondary intention healing?
Broader scar result of granulation
What type of scaring occurs with tertiary intention healing?
Wound is purposely left open
What type of injury is primary intention healing?
Little tissue loss.
Most surgical wounds heal by which intention?
Primary intention healing. (wound edges are directly next to each other)
How is a primary intention wound is closed?
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 and surgeons may pack the wound with gauze or use a drainage system.
How long will a tertiary intention scar be left open?
4-5 days.(where the wound is initially cleaned, debrided and observed before closure)
What is Keloid?
Excess collagen deposition in the skin forming a raised scar.
What is inflammation?
The reaction of the blood vessels, leading to the accumulation of fluid and leukocytes in the extravascular tissues
What is the function of inflammation?
A protective response- eliminate microbes and toxins- eliminate necrotic cells and tissues- prepare for tissue repair
What do neutrophils do?
First responder (acute inflammation) bacterial or fungal infection
What forms pus?
Increased activity and death of neutrophils
What general percentage of WBC’s do neutrophils make up?
60%
What do lymphocytes do?
Chronic inflammation- T cell and B cell response/activation
What general percentage of WBC’s do lymphocytes make up?
30%
What do monocytes do?
Long lived Phagocyte that present pathogen parts to T cells
What are monocytes when they are in tissue?
Macrophages
What general percentage of WBC’s do monocytes make up?
5-6%
What do eosinophils do?
Parasite and Allergic response
What general percentage of WBC’s do eosinophils make up?
2-3%
What do basophils do?
Allergic and antigen response and releasing the chemical histamine
What are basophils when they are in tissue?
Mast Cells
What general percentage of WBC’s do basophils make up?
<1%
What is the order from largest to smallest of the WBC’s?
NeutrophilsLymphocytesMonocytesEosinophilsBasophils(Never Let Monkeys Eat Bananas)
Where do T lymphocytes mature?
Thymus
Where do B lymphocytes mature?
Bone maroow
Are thrombocytes WBCs?
No they are platelets
What is the function of thrombocytes?
To plug up holes
What is the life span of an RBC?
120 days
What is the life span of WBC?
days to years
What is the life span of a platelet?
8 days
What are the two types of inflammation?
Acute and Chronic
What is the duration and onset speed of acute inflammation?
Rapid onset and short duration (min/hours/days)
Is there edema with acute inflammation?
Yes
What type of leukocyte is predominantly present with acute inflammation?
Predominantly neutrophils, but also eosinophils and antibody mediated
What is the duration and onset speed of chronic inflammation?
Slower onsetLong duration (wks, months, years)
What are some characteristic appearances of chronic inflammation?
Presence of new blood vessels, fibrosis, and tissue necrosis
What type of leukocyte is predominantly present with chronic inflammation?
Predominantly macrophages and lymphocytes
What are the key signs and symptoms of acute inflammation?
1) Redness2) Heat3) Swelling4) Pain5) Loss of function
What is the Latin term for redness?
Rubor
What is the Latin term for heat?
Calor
What is the Latin term for swelling?
Tumor
What is the Latin term for Pain?
Dolor
What is the Latin term for Loss of function?
Functio laesa
What vascular changes occur with inflammation?
1) Vascular dilation and increased blood flow (causing erythema and warmth)2) Extravasation and deposition of plasma fluid and proteins (edema)3) Leukocyte emigration and accumulation in the site of injury
What is the net flow of fluid of microvasculature in normal circulation?
Small flow out of the precapillary arteriole but returned in the precapillary venuole
What happens to the net flow of the microvasculature with acute inflammation?
Arteriole pressure is increased and the mean capillary pressure is increased due to arteriolar dilation. The venous pressure increases and the osmotic colloidal pressure is reduced due to protein leakage across the venule which results in an excess of extravasated tissue
What is oncotic pressure?
Pressure bringing in fluid into vasculature from tissue due to albumin concentration
What causes oncotic pressure?
Albumin concentration
What controls arteriole pressure?
Sphincters of muscles that clamp off blood flow
What collects the small flow out of the capillary bed?
Lymphatic system
What is hyperemia?
Increased blood flow
What occurs with the precapillary sphincter during normal circumstances?
The precapillary sphincters are closed
What occurs with the precapillary sphincter during acute inflammation?
The precapillary sphincters are open
During normal flow how are the RBC’s and platelets and neutrophils distributed?
Scattered
Where in a circulatory vessel is the flow the fastest?
The middle because of laminar flow
What is the term for the stacking of RBCs as they move towards laminar flow?
Rouleaux of RBC
What does marginalization of neutrophils refer to?
When the neutrophils are pushed aside and moving towards the endothelium
What is the rouleaux relation to erythrocyte sedimentation rate?
It elevates the ESR
What are the steps of leukocyte extravasation?
1) Margination2) Pavementing3) Extravascular migration
What is the main leukocyte of margination?
Neutrophils
What are the parts of the pavementing stage of leukocyte extravasation?
1) rolling2) tight binding3) diapedesis/migration
What are some parts of tight binding of the pavementing stage of leukocyte extravasation?
1) integrin activation2) stable adhesion
What occurs in extravascular migration?
Chemokines and cytokines direct the leukocyte to go to specific area
What are the 3 steps of phagocytosis of a particle?
1) recognition and attachment- microbes bind to phagocyte receptors2) engulfment- phagocyte membrane zips up around microbe3) killing and degradation- fusion of phagosome with lysosome- killing of microbes by lysosomal enzymes in phagolysosome
What 2 groups are the mediators of inflammation divided into?
1) plasma derived2) cell derived
Do mediators of inflammation act only on a single cell?
No, they are multifunctional and act on many cells and tissues
Are mediators of inflammation biochemically the same or diverse?
Biochemically diverse including biogenic amines, peptides and arachidonic acid derivatives
What is a histamine?
Biogenic amine that is from a cell derived source (stored in cell)
Where histamines released from?
Platelets and mast cells
What is the function of histamine?
Stimulates retraction of endothelial cells of the venules and leads to gaps therefore increased permeability
Is the action of histamine short or long and why?
The action of histamine is short because it is inactivated by histaminase
What vitamin stabilizes mast cells?
Vitamin C, during an acute response
What is bradykinin?
Plasma protein in the liver that is derived from kininogen through the enzymatic action of kallikrein?
what is Kallikrein do and what is it activated by?
Kallikrein acts on the clotting and fibrinolytic systems of the blood and activated by Hageman factor
What does bradykinin induce?
Pain
What is the relationship between bradykinin and histamine?
They both have a similar action
What were the mast cells called before they exited the blood vessel?
Basophils
What does neoplasia mean?
New Growth
What does tumor mean?
Swelling, formation of masses
What does cancer mean?
Tissue invasion appearance like crawling crab
What does oncology mean?
Study of Swelling
What does carcinoma in situ mean?
Means “in its place” but is a tumor that has not penetrated the basement membrane
Are all tumors a neoplasia?
Yes
Is a neoplasia always a tumor?
No, sometimes there’s no distinct mass as in leukemia or malignant disease of bone marrow
What are the 3 types of reversible plasias?
1) Hyperplasia2) Metaplsia3) Dysplasia
What are the 3 types of irreversible plasias?
1) anaplasia2) neoplasia3) desmoplasia
What is anaplasia?
Irreversible Abnormal cells lacking differentiation; like primitive cells equated with undifferentiated malignant neoplasms
What is desmoplasia?
Irreversible Fibrous tissue formation in response to neoplasm
What are the two classifications of tumors?
BenignMalignant
How are tumors classified?
Histologically
How do the growths of benign and malignant tumors differ?
Benign tumors are slow and expansive and malignant tumors are fast and invasive
Are both benign and malignant tumors metastatic?
No, Benign tumors are not metastatic
How do the external surface features of benign and malignant tumors differ?
Benign = smoothMalignant = irregular
Do both benign and malignant tumors have capsules?
No, only benign tumors have capsules
Are both benign and malignant tumors capable of necrosis?
No, only malignant tumors are capable of necrosis
Are both benign and malignant tumors capable of hemorrhage?
No, only malignant tumors are capable of hemorrhage
How does the architechture of benign and malignant tumors differ?
Benign = resembles normal tissue of originMalignant = Does not resemble normal tissue of origin
How does the cells of benign and malignant tumors differ?
Benign = well differentiatedMalignant = Poorly differentiated
How do the nuclei of benign and malignant tumors differ?
Benign = normal size and shape; uniformMalignant = pleomorphic (variable in shape)
How does the mitosis of benign and malignant tumors differ?
Benign = few in mitosisMalignant = many and irregular
What is a regular nuclear to cytoplasmic ratio?
1:06
What does a nuclear to cytoplasmic ratio of 1:2 or 1:3 signify?
It means they are neoplastic
What does metastasis mean?
Change in position
What are the main pathways of metastasis?
1) lymphatics2) blood (hematogenous spread)3) Seeding surface of body cavities (transcoelomic spread)
What are some other pathways of metastasis?
Intraepithelial
What are the steps of hematogenous metastatic cascade?
1) primary tumor2) metastatic clone evolves3) proliferation of the clone and invasion of vessel4) transport by circulation5) emobilization6) invasion7) new tumor formation at the site of metastasis
What is transcoelomic spreading?
Direct seeding of a cavity by neoplastic cells within that cavity therefore there is no plane of resistance to spreading
What is intraepithelial spread?
1) Tumor cells infiltrate between the cells of normal epithelium without invading the underlying stroma
What is the best example of intraepithelial spread?
Paget’s disease of the nipple where cells of ductal carcinoma in situ grow into nipple skin and resemble eczema
What is tumor-induced angiogenesis?
The biologic role of tumors to overcome limitation of nutrient and oxygen delivery
What do mesenchymal tumors with the -oma ending mean?
It stands for a mesenchymal benign tumor
What do mesenchymal tumors with the -sarcoma ending mean?
It means that it is a mesenchymal malignant tumor
What do epithelial tumors with the adenoma ending mean?
It is a benign epithelial tumor
What do epithelial tumors with the carcinoma ending mean?
It is a malignant epithelial tumor
What are the three exceptions to the “oma” being benign rule? Why?
LymphomaMultiple myelomaGliomaBecause they only exist via blood cells, lymph system and glial cells
What is common between squamous cell carcinoma and adenocarcinoma?
They both are surrounded by non-neoplastic stroma
What are some tumors of blood cells and lymphocytes?
LeukemiaLymphomaMultiple Myeloma
What are some tumors of neural cells?
GanglioneuromaNeuroblastoma
What are some tumors of glial and nueral suporting cells?
Glioma and meningioma
What are some germ cell tumors?
Teratoma, embryonal carcinoma and seminom/dysgerminoma
What are blastomas?
Blastomas are malignant tumors composed of embryonic cells originating from embryonic primordia
What is a teratoma?
Teratomas are derived from germ cells and contain tissues that are formed from all three germ layers: etoderm, mesoderm and endoderm
What are eponymic tumors?
These tumors carry the name of physicians who have described them first
What does Hodgkin’s disease affect?
lymph nodes
What does Ewing’s sarcoma affect?
Bones
What does Kaposi’s sarcoma affect?
Skin
What is tumor staging based on?
Clinical assessment during gross examination, surgery, x-ray examinations
What is the grading of tumors based on?
Based on histologic examination
What does the TNM system of staging take account for?
T = size of tumorN = presence of lymph node metastasesM = Distant metastases
What is the grading scale of the TNM system?
0-4 in each category TNM
What grading of M signifies metastases?
a 1 represents metastasis
What do the roman numeral stages of tumor range from?
0 to IV
What is a stage 0 tumor?
A carcinoma that is in situ
What is a stage I cancer?
Cancer that is localized to one part of the body
What is a stage II cancer?
A locally advanced (same as stage III but specific criteria differ according to diagnosis)
In Hodgkin’s disease what is the difference between stage II and stage III?
Stage II: lymph nodes on only one side of the diaphragmStage III: lymph nodes above and below the diaphragm
What is a stage IV cancer?
Canvers that have metastasized or spread to other organs or throughout the body
what is the Ann Arbor staging for? and what stages are there?
For lymphomas ranging from stage I - IV
What is a stage I in the Ann arbor staging?
Cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms
What is a stage II in the Ann arbor staging?
Cancer is located in two separate regions, an affected lymph node or organ within the lymphatic system and a second affected area, and that both affected areas a confined to one side of the diaphragm (ie: both are above the diaphragm or both are below the diaphragm)
What is a stage III in the Ann arbor staging?
Cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen
What is a stage IV in the Ann arbor staging?
Diffuse or disseminated involvement of one or more extralymphatic organs, including any involvement of the liver, bone marrow, or nodular involvement of the lungs
What does the tumor grades range from?
Grade I - III
What is tumor grading based on?
Histologic examination
What is a grade I tumor?
well differentiated
What is a grade II tumor?
Moderately well differentiated
What is a grade III tumor?
undifferentiated
Overall, which has more predictive value, grading or staging of tumors?
Staging
Is the difference between normal and malignant cells qualitative or quantitative?
Quantitative
Are cancer cells more or less adapted to survive unfavorable conditions and are they more or less differentiated than normal cells?
Cancer cells are less differentiated and more adapted to survive under unfavorable conditions as they require less oxygen to survive
In which gender has deaths from lung cancer plateaued? and which is continuing to rise?
Males = plateauFemales = rise
Is cancer the leading cause of death in the US?
No it is number 2, heart disease is 1st
Define Incidence
The number of new cases that have been registered over a specific time in a defined population
Define prevalence
The number of all cases, new and old, within a defined population at a defined time
Define Mortality
The number of deaths attributed to cancer during a specified period in a defined population
Define morbidity
number suffering from a disease that has been registered over a specific time in a defined population
What is the most important risk factor and most common initial symptom for lung cancer?
Smoking -> Cough
What is the most important risk factor and most common initial symptom for breast cancer?
Family history of cancer -> lump
What is the most important risk factor and most common initial symptom for colon cancer?
Family history of colonic polyps -> blood in stool
What is the most important risk factor and most common initial symptom for cervix cancer?
Promiscuity (early intercourse or multiple partners) -> vaginal bleeding (spotting)
What is the most important risk factor and most common initial symptom for uterus cancer?
Hormonal: imbalance and treatment -> vaginal bleeding
What is the most important risk factor and most common initial symptom for skin cancer?
Sun exposure -> sun lesion
What is the most important risk factor and most common initial symptom for prostate cancer?
Old age -> dysuria
What cancer has the highest incidence in men?
Prostate
What cancer is the second highest incidence in men and women?
Lung & bronchus
What cancer is the third highest incidence in men and women?
Colon & rectum
What cancer has the highest incidence in women?
Breast
What cancer has the highest mortality in men and women?
Lung & bronchus
What cancer has the third highest mortality in men and women?
Colon & rectum
What cancer has the second highest mortality in men?
Prostate
What cancer has the second highest mortality in women?
Breast
Where does metastatic cancers usually travel to?
LiverLungBrainBone
What does metastatic cancer usually indicate?
A poor pronosis
How does the insertion part of viral carcinogens?
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
What are the different types of human carcinogenic viruses?
DNA viruses and RNA viruses
What are some examples of human carcinogenic DNA viruses?
- Human Papilloma virus- Epstein-Barr virus- Hepatitis B and C virus- Kaposi’s sarcoma-associated herpesvirus
What are the types of HPV that can cause cervical, penile/anal carcinoma?
16 and 18
What can epstein-barr virus cause?
Burkitt’s lymphoma (B cell neoplasia)Nasopharyngeal carcinoma
What can Hepatitis B and C virus cause?
Liver cancer
What can Kaposi’s sarcoma-associated herpesvirus cause?
Kaposi’s sarcoma, a type of skin cancer
What is a type of RNA virus and what can it cause?
Human T-cell leukemia/lymphoma virus and it can cause adult T cell leukemia (HIV group)
What are human oncogenes?
Homologous to viral oncogenes and thus called cellular oncogenes
What do human oncogenes represent?
Represent activated normal genes (proto-oncogenes)
How does an oncogene function?
An oncogene has gained function and becomes a cancer-inducing agent
How many damaged allele does it require to activate an oncogene?
Only 1 damaged allele
What are different ways of transformation of proto-oncogenes into oncogenes?
1) point mutation2) gene amplification3) chromosomal rearrangement4) insertion of viral oncogene
What do tumor suppressor genes do?
Protect the cells against activated or newly acuired oncogenes
What happens to a tumor suppressor gene that has lost function?
It is no longer a cancer-inhibiting agent
How many tumor suppressor gene alleles out of the two need to be lost in order for expression of disease?
Both alleles
What are different types of Hereditary cancer?
1) Neurofibromatosis type 12) familial adenomatous polyposis coli3) Wilms’ tumor4) Skin tumors in xeroderma pigmentosum5) chromosomal fragility syndromes (Bloom’s syndrome, Fanconi’s syndrome)
What are some cells that pose an immune response to tumors?
1) Natural Killer Cell2) Macrophage3) Neutrophil4) B lymphocyte5) Cytotoxic T lymphocyte
What is the immunotherapy of Cancer?
1) some tumors involute spontaneously under the influence of immune factors2) BcG (attenuated tuberculosis bacillus of calmette and Guerin) is used for treatment of bladder cancer3) Tumor vaccines are used for treatment of melanoma and renal cell carcinoma
Should tumor markers be used as a primary tool for cancer diagnosis?
No
What should tumor markers be used for?
Confirming a diagnosis, to monitor for tumor recurrence and to monitor response to therapy
What is the Tg tumor marker detect?
Thyroglobulin. Thyroid cancers
What is active hyperemia?
Dilatation of arterioles leading to blushing, exercise, inflammation
What is passive hyperemia?
Venous back pressure; often associated with hydrostatic edema, cyanosis- heart failure - pulmonary edema and heart failure cells
What does a chronic passive congestion of lungs lead to?
Leads to edema and RBC extravasation into alveoli
What is a chronic passive congestion of lungs accompanied by?
Accompanied by anoxia & often results in pulmonary fibrosis
In a chronic passive congestion of the lungs, what does an alveolar macrophage do?
Alveolar macrophages take up RBC & degrade hemoglobin = hemosiderin accumulation
Cardiac hemorrhage is often what? And what is it caused by?
- often fatal
- MI, Gun Shot Wound, stabbing wound
What is an aortic hemorrhage caused by?
- MVA (organs kee moving at a high speed and rips off part of aorta via ligamentum arteriosum - weakness due to copper deficiency -> aneurysm
What will an arterial hemorrhage look like? What causes it?
- penetrating wound, fractured bones
- presents as a bright red, pulsating/squirting
What will cause a capillary hemorrage? What does it do to venous pressure?
- Trauma, weakness due to vitamin C (scurvy) -increase in venous pressure
With the venous, how does it present as a hemorrhage?
Dark/bluish color, oozing
In a hemorrage what are some signs and symptoms?
- Intracerebral hemorrhage
- Hematemesis or hemoptysis
- Cardiac hemorrhage
- Venous hemorrhage
- Aortic hemorrhage
- Capillary hemorrhage
- hematochezia or melena (from anus)
- Hematuria
What are some clinically important forms of hemorrhage?
- skin/surface hemorrhage
- large accumulation of blood in body cavities/space
- hemoptysis
- epistaxis
What are some different types of skin/surface hemorrhage?
- petechia
- purpura
- ecchymosis
What is a petechia?
<1 mm and speckles of blood vessels
What is purpura?
Between 1 mm- 1cm and larger blotches
What is ecchymosis?
Large/blotchy bruises
What are some large accumulation of blood in body cavities/spaces?
Hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis
What is a hemoptysis?
Respiratory tract/expectoration of blood
What is a epistaxis?
Nose bleed
What is hematemesis?
Vomiting blood
What is hematochezia
anorectal bleeding
what is melena
passage of black blood in stool
what is hematuria
blood in urine
What is metrorrhagia?
bleeding not related to normal monthly menses
what is menorrhagia?
Profound menstrual bleeding
What happens in a massive hemorrhage?
Blood loss, hypovolemic shock, exsanguination, death
If <500 ml of blood is lost what happens?
homeostatic compensation but it is reversible
If 1000-1500 ml of blood is lost what happens?
Circulatory shock
If >1500 ml of blood is lost what happens?
Lethal
What are some of the types of hemorrhage?
- Massive hemmorhage
- Hematoma
- Intracerebral hemorrhage
- Chronic hemorrhage
What can an intracerebral hemorrhage lead to?
Stroke, death
What can a chronic hemorrhage lead to?
Slow blood loss, iron deficiency anemia (70 ml for normal menstruation)
Which hemorrhage has a better outcome, Subdural or epidural hemorrhage?
A subdural hemorrhage because the lower pressure veins bleed more slowly than arteries
What Is the different types of pathogenesis causes of Edema?
1) Inflammatory2) Hydrostatic3) Oncotic4) Obstructive5) Hypervolemic
Why does inflammatory lead to the pathogenesis of edema?
Increases permeability & hyperemia
How does hydrostatic lead to the pathogenesis of edema?
Increased arterial pressure (hypertension)Increased venous back pressure (heart failure)
How does the oncotic pressure lead to the pathogenesis of edema?
Hypoalbuminemia due to:-loss/proteinuria- decreased protein synthesis
How does the obstruction lead to the pathogenesis of edema?
- Most often b tumor or chronic inflammation- Filaria (worm) -> elephantiasis
How does hypovolemia lead to the pathogenesis of edema?
Usually d/t sodium and water retention:- kidney function, renin, angiotensinogen, & aldosterone- Kidney disease -> increased renin release -> angiotensinogen -> increased aldosterone -> increased Na retention -> increased water retention
What are some clinical forms of edema?
1)Cerebral edema2) Pulmonary edema (d/t left-sided heart failure, post-surgery)3) Pitting edema of the lower extremities4) Periorbital (facial) edema5) Hydrothroax6) Hydropericardium7) Hydroperitoneum (ascites)8) Anasarca (Extremegeneralized edema)
What is TORCH(ES) syndrome?
a medical acronym for a set of perinatal infections (i.e. infections that are passed from a pregnant woman to her fetus).
When should we test for TORCH(ES) syndrome?
Early in pregnancy.
What will the T in Torches syndrome stand for and how do we get it?
Toxoplasma we get it from cat shit so stay away from Julie.
What will the O in TORCHES syndrome stand for?
Others that are less common like Epstein-Barr virus, Varicella virus, Listeria monocytogenes, leptospira.
What will the R in TORCHES syndrome stand for?
Rubella.
What will the C in TORCHES syndrome stand for?
Cytomegalovirus (CMV).
What will the H in TORCHES syndrome stand for?
Herpesvirus.
What will the (ES) in TORCH(ES) syndrome stand for?
Syphylis.
What does rubella cause?
1) Small (microcephaly)/strucuraly abnormal brain2) Heart defects.
What will Toxoplasma cause?
1) Microcalcification of basal ganglia and dilation of lateral ventricles (hydrocephalus)2) CNS defects.
What will cytomegalovirus (CMV) cause?
The same as Toxoplasma.
What will herpesvirus affect?
1) CNS defects2) Skin lesions.
What are 2 types of chromosomal anomalies?
Structural and numerical anomalies
What is Aneuploidy?
Loss or gain of chromosomes.
What are 2 types of aneuploidy?
Hyperdiploidy- 46+1 or 46+2. Hypodiploidy- 46-1 or 46-2.
What is monosomy?
Missing one chromosome
What is Trisomy?
Gaining an extra chromosome (3 of one chromosome)
What is the most common risk factor for Down syndrome?
Paternal age increases risk of having a baby born with down syndrome
What disorder is associated with Down syndrome?
Trisomy 21 (D= drinking age 21)
What disorder is associated with Edward’s syndrome?
Trisomy 18 (E = election age 18)
What disorder is associated with Patau’s syndrome?
Trisomy 13 (P = puberty age 13)
Of the 3 disorders Down, Edward’s and Patau’s, which one is most common?
Down Syndrome
What happens to a baby’s hands with down syndrome?
Simian crease.
Down syndrome or trisomy 21 leads to what mental issues?
Most commonly leads to mental retardation
How will down syndrome affect the head?
Flat facial profile and epicanthic folds
How will down syndrome affect the heart?
Congenital heart defects like septum primum due to endocardial cushion defects.
How will down syndrome affect the limbs and feet?
HypotoniaA gap between first 2 toes.
What is the life expectancy with edwards sydnrome aka trisomy 18?
less than 1 year.
What will edwards syndrome cause?
Severe mental retardation.
How will edwards syndrome affect the head?
1) Prominent occiput2) micrognathia (small jaw)3) low set ears.
How will Down syndrome affect the umbilicus and intestines?
Causes umbilical hernia and intestinal stenosis
What is the incidence of down syndrome?
1 in 700 births
How will edwards syndrome affect the heart?
Congenital heart defects will be present.
How will edwards syndrome affect the hands and feet?
Hands- Clenched hands Feet- Rocker-bottom feet.
What is the life expectancy with down syndrome?
45-50 years old
What is the incidence of Edward’s syndrome?
1 in every 8000 births
What some limb changes with Edward’s symptoms
Limited hip abductionRocker bottom feet
What is the incidence of Edward’s syndrome?
1 in 8000
What are some neurological issues with patau symptoms?
Microcephaly and mental retardation
What are some head changes with patau symptoms?
Cleft lip and palateMicrophthalmia
What are some limb issues with patau symptoms?
1) Polydactylyl2) Focker -bottom feel
What is the incidence of Patau syndrome?
1 in 15000
What is the life expectancy of Down syndrome?
45-50
What is the life expectancy of Edwards syndrome?
<1 year
What is the life expectancy of Patau syndrome?
<1 year
In which disorder(s), (Downs, Edwards, Patau) does mental retardation occur?
Yes, severe in Edwards and Patauand the most common cause is Down Syndrome
What are some other disease risks for Down Syndrome?
ALL, Alzheimer’s >age 35
What are two disorders that are caused by abnormalities of sex chromosomes?
1) Turner syndrome2) Klinefelter syndrome
Who can get turner’s syndrome and who can get Klinefelter’s syndrome?
They are abnormalities of sex chromosomes so only females can get Turners and Only males can get Klinefelter’s syndrome.
Pathogenesis of sex chromosome abnormalities are due to what?
Nondisjunction.
What is nondisjunction?
Failure of paired chromosome to separate.
How common is Turners syndrome?
1 in every 3,000 female births.
What are the symptoms of Turners syndrome? (It’s super long, sorry)
1) Short stature2) heart- shaped face3) low posterior hairline4) webbing of neck5) heart disease and coarctation of aorta6) broad chest and widely spaced nipples7) pigmented nevi (moles)8) cubitus valgus(elbows turned in)9) streak ovaries, hypoplastic uterus, amenorrhea10) peripheral lymphedema at birth.
Are Turner’s considered male or female?
Female presentation
What symptoms will Klinefelter’s syndrome present with?
1) Tall long arms and legs2) lack of beard body hair and pubic hair3) gynecomastia4) female like hips5) testicular atrophy.
Is Klinefelter syndrome considered male or female?
Male presentation (based on penis presentation)
What type of disorder is spherocytosis?
A congenital RBC membrane disorder. IT is an autosomal dominant disease.
What are 3 possible symptoms of spherocytosis?
anemia, jaundice, splenomegaly.
How is spherocytosis diagnosed?
requires demonstration of increased RBC osmotic fragility and negative direct antiglobulin test.
How often will spherocytosis patients less than 45 years old need a splenectomy?
Rarely.
With spherocytosis what causes RBC abnormalities?
Alterations in membrane proteins.
What alternations in membrane proteins of RBC happens with spherocytosis?
Surface area is decreased disproportionately to the intracellular content.
What will decreased surface area of a RBC membrane cause?
Flexibility needed for the cell to traverse the spleen’s microcirulation.
With western treatments how will spherocytosis be cured?
Splenectomy.
Presence of spherocytes in the peripheral blood smear suggest what?
- Hereditary spherocytosis (HS). 2. Autoimmune hemolytic anemia (AIHA).
When there are spherocytes in the peripheral blood smear how can you distinguish between hereditary spherocytosis or autoimmune hemolytic anemia?
Coomb’s test.
What will a negative and positive Coomb’s test mean?
Negative- Hereditary spherocytosis. Positive- Autoimmune hemolytic anemia.
Huntington’s disease is what type of disorder?
An autosomal dominant characterized by chorea and progressive cognitive deterioration.
How will Huntington’s disease be diagnosed?
Genetic testing.
What is treatment of Huntington’s disease like?
Supportative.
What type of relatives of patients with Huntington’s disease should be tested?
first-degree relatives.
Will Huntington’s disease effect males or females more?
Both equal.
What parts of the CNS will Huntington’s disease effect?
Caudate nucleus atrophies, medium spiny neurons in the corpus striatum degenerate, and levels of neurotransmitters gamma aminobutyric acid and substance P decrease.
What genes are effected with Huntington’s disease?
Gene on chromosome 4.
The gene on chromosome 4 (Huntington’s disease) will lead to what?
Abnormal repetition of DNA sequence CAG that codes for amino acid Glutamine.
The gene product of abnormal CAG codes that make glutamine leads to what?
a large protein called huntingtin and it has large stretches of polyglitamine residue.
How will the huntingtin protein lead to huntington’s disease?
Unknown.
The more CAG repetitions means what?
The earlier the disease begins and the more severe the effects.
What will huntington’s disease be like from generation to generation?
over time it leads to more severe phenotype and more CAG codes that make more polyglitamine residues.
How do Symptoms of Huntington’s disease develop?
Insidiously (inconspicuous or seemingly harmless way ).
When do Signs and symptoms of Huntington’s disease develop?
start between 35-50, but can develop before adulthood.
What are the signs and symptoms of Huntington’s disease?
Dementia or psychiatric disturbances, abnormal movements including tongue protrusion.
Death usually occurs how long after the first signs and symptoms of Huntington’s disease appear?
13-15 years.
What will the cause of death usually be with Huntington’s disease?
Coronary heart disease or pneumonia
What is the secondary or aquired immunodeficiency?
AIDS aquired immunodeficiency syndrome.
What will cause severe combined immunodeficiency, and what type of immunodeficiency is it?
It is primary and caused by a defect of lymphoid stem cells pre-B, Pre-T cells.
What is the most common type of primary immunodeficiency diseases?
Isolated deficiency of IgA.
What % of people have Isolated deficiency of IgA?
1 out of every 700 people
What is isolated deficiency of IgA like in the population?
Often asymptomatic.
What type of immunodeficiency disease is DiGeorge’s syndrome and what causes it?
It is a primary one caused by T-cell deficiency related to aplasia of thymus associated with aplasia of parathyroid glands.
What type of virus is HIV aka Human immunodeficiency virus?
RNA retrovirus.
AIDS infects what?
T helper Cells (CD4+).
Where is AIDS stored at?
Macrophages and related phagocytic cells.
What are the clinical presentations of HIV/AIDS?
acute illness, asymptomatic infection, persistent generalized lymphadenopathy.
What are 5 pahtologic findings in AIDS?
- Lymphadenopathy. 2. Kaposis sarcoma. 3. Nephrophaty. 4. Weakness. 5. oral thresh.
What type of infections happen with AIDS?
Opportunistic.
What 3 places are prone to opportunisitic infections?
- Lungs. 2. GI tract. 3. CNS.
What are the 3 tumors that develop with AIDS?
- Lymphoma of lymph nodes or GI tract. 2. Lymphoma of the CNS. 3. Kaposis sarcoma.
All antibodies are composed of what?
Light and heavy chains.
Which chains of antibodies are changeable and which chain is the same?
Light- same. Heavy are specific for each Ig.
What is another name for light and heavy chains?
Light-Fc. Heavy-Fab.
What is the largest Ig?
IgM.
What is the function of the IgM?
To neutralize microorganisms.
The IgM has how many complement binding sites?
five.
What is the first Ig to appear?
IgM.