Exam 3 Flashcards
For most cancers, the stage is based on 3 main factors:
- Tumor size and invasion
- Lymph node involvement
- Metastasis
TNM System:
T (1-4) - size and invasiveness of primary tumor.
N (0-3) - lymph node involvement
M (0-1) - tumor metastasis
—M0 = no evidence of metastasis
Grading:
Tumor grading is a system used to classify cancer cells in terms of how abnormal they look under a microscope and how quickly the tumor is likely to grow and spread. Look at cell characteristics.
After biopsy, tissue is examined for:
- Degree of Differentiation
- Extent of pleomorphism
- Frequency of mitosis/mitotic figures (growth fraction)
Grade (numbers)
G1: well-differentiated (low grade)
G2: moderately differentiated (intermediate grade)
G3: poorly differentiated (high grade)
G4: undifferentiated/anaplastic (high grade)
*grading systems are different for each type of cancer
Goals of cancer treatment fall into three categories:
- Curative (tries to completely irradiate)
- Controlling (tries to slow progression)
- Palliative (not aimed at a cure, tries to reducing suffering; pain management)
Cancer Treatments (listed)
Surgery Radiation therapy Chemotherapy Immunotherapy Bone marrow and stem cell transplants Gene Therapy Antiangiogenesis therapy Combination therapy
Surgery (cancer treatment)
removal of tumor - try for clean (negative) margins of resection
(take out whole area around with normal cells so there is a margin on normal cells around the tumor)
Radiation Therapy (cancer treatment)
ionizing radiation
localized beams of radiation directed toward tumor site
Chemotherapy (cancer treatment)
Anti-neoplastic chemicals. Tends to lose effect with time. Some tumors are resistant.
(works systemically - targets all labile cells, cells dividing at a high rate)
side effects: hair loss, nausea, fatigue, etc.
Interferes with mitosis of bone marrow
-bone marrow suppressed so it affects RBCs, WBCs, and platelets
Immunotherapy
attempts to use immune system to fight tumor
- interferon or interleukin 2 (IL2)
- monoclonal antibodies - block signals, mark for destruction
- vaccines - prophylactic (prevent virus = prevent cancer, for example, HPV) and therapeutic (teaches immune system to go and attack cancer by pulling cancer cells out and developing the vaccine and inserting it back in)
Bone Marrow and Stem Cell Transplants (cancer treatment)
Use other people’s marrow and/or stem cells to help cure certain diseases
Gene Therapy (cancer treatment)
Alteration of one’s genetic material to fight or prevent disease
(replace mutated genes to cure cancer)
(modify virus and insert to replace mutated DNA)
Antiangiogenesis Therapy (cancer treatment)
Target VEGF pathway
blocks VEGF receptors so blood vessels aren’t growing in tumors
Combination Therapy
Use of two or more therapies. Surgery and/or radiation first, followed by chemotherapy.
(most common/likely)
Prostate (Background Information
- Prostate gland is an encapsulated gland that secretes additional fluids into the seminal fluid
- It lies between the urinary bladder and the superior surface of the UG diaphragm
- The prostate gland can be broken down into various lobes; some of which are the anterior, posterior, and median lobes (which have clinical significance)
Anterior Lobe (prostate gland)
Fibrous and normally non-pathological in nature
Median Lobe (prostate gland)
Is famous for benign prostatic hyperplasia (NOT CANCER)
The lobe may undergo hyperplasia resulting in obstruction of the urethra and the visceral neck of the urinary bladder. (enlarges upward and closes in on urethra, squeezing off urethra)
Benign Prostatic Hyperplasia (BPH) - Signs and Symptoms
Urinary frequency, dysuria (difficult urination), and infection due to retention (cannot completely empty the bladder)
This condition begins at about 45 years of age, and occurs in 80% of all men by 80 years of age
BPH - Treatment
Take meds to shrink
Less than 10% require TURP
Posterior Lobe (prostate gland)
Most predisposed to malignant transformation (carcinoma of the prostate)
Prostate Cancer Statistics
Most common cancer in males (1 in 6 men)
Second most common cause of cancer-related deaths in males
Prostate Cancer Etiology
Poorly understood, but genetics and testosterone play a role
Risk factors include age (>70, rare before age 65), race (black people have higher risk), and heredity (dad/brother with cancer = 2x risk)
Prostate Cancer Pathology
85% originate in posterior lobe
Metastasizes through lymphatic vessels into adjacent structures: rectum, bladder, pelvic structures, vertebral column, liver, others.
Most often slow growing
Prostate Cancer Diagnosis
Medical History
Rectal (digital) exam
Confirmed by biopsy
PSA - positive test indicates potential problems and further testing is needed (can have false positives - 2/3 who have elevated PSAs do not have cancer)
Prostate Cancer Treatment
Surgery
Radiation (can use permanent seeds)
Watchful Waiting (keep an eye on it and make decisions based on how fast it is growing)
- It is usually treated with a combination of radiation and hormone therapy with some type of surgery to remove the cancerous tissue.
- Depends on age of patient and characteristics of the tumor (grade of tumor)
Prostate Cancer Prognosis/Staging
Depends on detection stage of tumor growth
- T1 = not palpable - detected by biopsy
- T2 = tumor palpable (10 year survival rates as high as 80%)
- T3 = invasion outside capsule
- T4 = indications of metastasis (10 year survival rates from 50-0% depending on specific case)
*In general, the earlier you catch it, the better the survival rate
Prostate Cancer Screening
Offer men 50 or older get digital rectal exam (DRE) and PSA test/year.
- Make an informed decision about screening
- Stop screening at 75
Prostate Cancer (general overview)
Very common
Most often slow growing
PSA results are questionable
Treatment has many side effects
Cervical Cancer
A highly preventable type of cancer (highly treatable)
Incidence of cervical cancer is declining due to:
Early detection and now, prevention
Cervical Cancer Etiology
Considered a STD.
Virtually all are caused by infection with Human Papilloma Virus (HPV) passed through skin to skin contact
asymptomatic
In 90% of cases, the immune system clears HPV within two years
Low risk HPV results in genital warts
HPV Infection
Mainly asymptomatic
In 90% of cases, the immune system clears HPV within two years
Low risk HPV results in genital warts
Types 16 and 18 (high risk HPV) cause 70% of all cervical cancers
Cervical Cancer Risk Factors
Sexual intercourse at early age (higher risk because of likelihood of more partners)
Multiple sex partners
Smoking
Cervical Cancer Signs and Symptoms
Asymptomatic, vaginal bleeding, pain during intercourse, metastatic signs and symptoms depending on site
Cervical Cancer Pathogenesis
A squamous cell carcinoma-
- Exocervix
- Endocervix
- Transformation zone
Exocervix
Projects into superior vagina and is covered with stratified squamous epithelium
Endocervix
Portion towards uterine body and is lined with columnar epithelium
Transformation Zone (cervix)
Where two epithelia meet. Site of most cervical carcinomas
Stages of Cervical Intraepithelial Neoplasia (CIN)
PRE-CANCEROUS
CIN 1 = mild dysplasia. Low grade lesion
CIN 2 = Moderate dysplasia. High-grade lesion
CIN 3 = Severe dysplasia in >2/3 of cells; carcinoma in situ (CIS)
Stages of Cervical Carcinoma and Prognosis
Stage 0 = CIS
-5 year survival up to 100%
Stage 1 = tumor confined to cervix
-5 year survival ~85%
Stage 2 = Invasion to adjacent structures; not reaching pelvic wall or middle third of vagina.
-5 year survival ~75%
Stage 3 = Invasion to lower 1/3 of vagina or wall of pelvis.
-5 year survival ~35%
Stage 4 = Extension to bladder or rectum or structures beyond pelvis
-5 year survival ~10%
Cervical Cancer Diagnosis/Screening
Pap smear detects dysplastic cells in exo- and endocervix
HPV testing
Cervical Cancer Treatment (listed)
Depends on progression of pathology
Cone Biopsy/Leep Procedure
Hysterectomy
Pelvic Exenteration
Cone Biopsy/Leep Procedure
Used to examine a portion of both exo- and endocervical tissue
Hysterectomy
Removal of uterus
Used in cases of advanced cancer
Pelvic Exenteration
Removal of all pelvic viscera
Last resort to reduce tumor burden
-Can include radiation along with surgery
Cervical Cancer Prevention
- Avoid HPV (and detect)
- Gardasil - protects against high and low risk; for boys and girls from age 9-26
- Lifestyle - ABC’s - Prevent precancerous from becoming cancerous - EARLY DETECTION!
- pap smear at age 21
- pap and HPV testing at age 30
- >65 can stop
1/2 of all cervical cancers are diagnosed in women who have never been screened (US)
Breast Cancer
70% of cases occur in women over age 50
Etiology (Breast cancer)
Idiopathic
Specific Genetic Link: BRCA-1 and BRCA-2 genes
-80% chance of developing cancer in their lifetime
Human epidermal growth factor receptor-2 (HER-2/neu) amplified in up to 30% of breast CA which indicates an aggressive tumor
p53 mutations
Other:
- family history of breast cancer
- radiation exposure
- premenopausal women over age 45
- obesity
- early onset menses/late menopause
- never pregnant
- first pregnancy after age 35
- high fat diet
- endometrial or ovarian cancer
- alcohol use
Breast Cancer Classification
Classified by tissue of origin and location of the lesion
Lobular CA is within the lobes
Ductal CA is within the ducts = MOST COMMON FORM
Inflammatory CA (rare) grows rapidly and causes overlying skin to become edematous, inflammed, and indurated
Also classified as invasive vs non-invasive
Invasive Breast CA
Breaks through the duct walls and encroaches on other breast tissue
90% of breast cancer
Non-invasive Breast CA
Remains confined to ducts
Signs and Symptoms (Breast Cancer)
Thickening of the breast tissue, painless lump or mass
Nipple retraction or discharge, skin changes, redness
Growth rates vary - may take up to 8 years for lump to become palpable
Can spread via lymphatic or bloodstream to lungs and other breast
Diagnosis (Breast Cancer)
Breast self exam
Mammography can detect lumps too small to palpate
Fine needle aspiration or biopsy
Hormonal receptor assay (estrogen dependent?)
Ultrasound: fluid or solid?
Chest X-rays for Mets
Scans of bones, brain, liver, etc.
Breast Cancer Stages
Stage 1 = T1N0M0
Stage 2 = A. T2N0M0, B. T1N1M0
Stage 3 = A. T3N2M0, B. T1N3M0
Stage 4 = T3N3M1
Breast Cancer Treatment (listed)
Lumpectomy Partial mastectomy Total mastectomy Modified radial mastectomy Hormonal Therapy Herceptin
Lumpectomy
For small well defined lesions. Followed by radiation.
Partial Mastectomy
Remove tumor and region of normal tissue. Followed by chemo or radiation
Total Mastectomy
Removal of entire breast. Followed by chemo or radiation
Modified Radial Mastectomy
Removal of entire breast, lymph nodes, lining of chest wall muscles. Chemo and radiation follows.
Hormonal Therapy
Lowers levels of estrogen (tamoxifen)
Herceptin
Antibody that selectively binds to the HER-2 oncogene. Inhibits proliferation of tumor cells that overexpress HER-2
Hemodynamic disorders arise from:
disruptions in normal blood flow
Hemostasis
Normal hemostatic mechanism to maintain the fluidity of the blood in the vascular system and yet allow the rapid formation of a solid plug to close a vessel defect.
Clotting at an appropriate site
Involves fibrin formation when we have the threat of blood loss
Thrombus
Solid mass of platelets, cells, and fibrin formed within an intact vessel.
Clotting at an inappropriate site.
Thrombus Morphology - Arterial
Granular and friable mass
Attached to endothelium
Lines of Zahn - striations (layers)
-formed during flow
“White Thrombus”
(lots of fibrin, few RBCs)
Thrombus Morphology - Venous
Dark red, long, may form cast
Loosely attached to endothelium
Due to stasis
“Red Thrombus”
Post-mortem clot - blood stops flowing, forms “jelly” like clot
Embolus
Abnormal mass moving in the blood stream
Embolism
Sudden occlusion of an embolus
May be solid, liquid, or gas
Most common will be thromboemboli
Factors that Predispose Thrombosis
Virchow’s Triangle:
- Endothelial damage (vessel)
- Stasis or turbulence of flow/disturbance in flow
- Hypercoagulation (blood)
Endothelial Damage
Disruption in the endothelium leads to exposure of subendothelial collagen
(blood (platelets) stick to collagen)
More common in arteries than in veins
-Hemodynamic Stress, atherosclerosis, trauma
Endothelial Damage can occur in the veins due to inflammation, iatrogenic (caused by medical intervention), or trauma
Hemodynamic Stress (endothelial damage)
Wear and tear
Flow of blood stressing and causing endothelium to tear
Hypertension damages endothelium and exposes collagen
Athersclerosis (endothelial damage)
Vascular disease
Deposition of fatty plaque (under endothelium) thickens wall
Blood doesn’t flow smoothly and can damage endothelium more
Trauma (endothelial damage)
Physical injury
ex) crushing type injury, smoking, bacteria
Disruption in Normal Flow
The two most common are turbulence of flow and stasis of flow
Bifurcations: splitting/branching
Plaque (atherosclerosis)
Aneurysms (bulging wall of blood vessel - worried about it rupturing)
Atrial Fibrillation
Arrhythmia leading to stasis
blood not flowing effectively - can lead to thrombus formation - thrombus can move
Stasis
Sluggish flow allows for clotting factors to accumulate and increases blood contact with endothelium
Mural Thrombus
Thrombi can form over an infarcted region on the ventricular wall
Saddle Thrombus
Straddles the bifurcation of pulmonary trunk
Venous Thrombosis/Thrombophlebitis/DVT favored by:
Virchow’s Triad - p501
- post op recovery, bed rest, CHF
- trauma, IV drug use
- travel
- pregnancy
Small can be asymptomatic
Large can cause edema, pain, cyanosis, ischemia
DVT Complication
Pulmonary Embolism (PE)
Massive PE can cause cardiovascular collapse (CV) and/or pulmonary collapse
A significant cause of mortality
Treatment and Prevention of DVT
Early ambulation
Pneumatic compression
Anticoagulants/thromboembolytics - like heparin
Vena cava filter (not common)
Hypercoagulability States
Birth control pills Pregnancy Cancer Liver disease Genetic Defect
A general rule: In arteries, thrombi can form in areas of injury or turbulent flow. In veins, thrombi form in areas of stasis.
Sequela of Thrombosis
- Resolution/Dissolution
- Infarction
- Embolus
- Aneurysm
Resolution/Dissolution (Sequela of Thrombosis)
Rapid shrinkage or complete lysis
-via natural anticoagulants, i.e. plasmin (dissolves fibrin)
Infarction
Region of necrosis caused by ischemia. A thrombus can either narrow or occlude the lumen of a vessel leading to ischemia/infarction
Examples: MI or CVA, renal artery, mesenteric artery, leg
Occlusion of the coronary arteries
Myocardial Infarction (MI)
Occlusion of the cerebral arteries
Cerebral Vascular Accident (CVA) - stroke
Infarction Outcome Depends On:
- Tolerance to Hypoxia
- Tissue Vasculature
- –Anastomoses (connections) allow for an alternate route (ex: Circle of Willis) - Rate of Occlusion
- –Slow occlusion allows for collateral circulation to develop - Occlusion Duration
- –length of ischemia (advertisement: D2B time 55 minutes and decreasing)
Embolism
The sudden occlusion of a traveling mass (embolus)
Sites of Origin and Probable Embolism Site
Systemic - brian, kidneys, liver, intestines, basically anywhere
Venous - end up in LUNGS
Aneurysm
Localized dilation of a blood vessel
Most common in the aorta (because of high pressure)
Types of Aneurysms (listed)
Berry
Fusiform
Dissecting
Berry Aneurysm
Small spherical dilation usually found in Circle of Willis
lots of turbulence, more of a tendency to clot
Fusiform
Entire circumference of vessel
dilation of entire vessel; common in aorta, especially abdominal aorta
Dissecting
(pseudoaneurysm)
Layers of the vessel wall separate and fill with blood
(walls separate and blood flows between; chisel on vessel wall; common in aorta due to high pressure)
Can sometimes lead to ruptured aorta and blood flows into pericardial sac which leads to cardiac tamponade
Cardiac Tamponade
Blood filled pericardial sac and compresses heart -> cardiac arrest
Pathogenesis/Etiology (Aneurysm)
Congenital Defect (born with it - not common)
Trauma (crushing injuries, car accident, weakening of vessel walls, etc.)
Infection (bacteria, for example, syphilis used to do this)
Atherosclerosis - most common
Signs and Symptoms (aneurysm)
Asymptomatic (most often)
Sequela and Hemodynamic Effects (aneurysm)
Thrombus
Compression
Rupture
Treatment of Aneurysms
Grafts (takes the pressure off the aneurysm)
Endovascular Coiling (put in coil to fill in aneurysm)
Clipping (cut it off)
Meds to Prevent Enlargement
Watchful Waiting
Signs and Symptoms of Blood Disease
Fatigue (RBC) Pallor (RBC) Infection (WBC) Tachycardia (RBC) Hyperphea/Dysphea - increase respiration rate/trouble breathing (RBC) Angina (RBC, platelets) Cyanosis (RBC) Petechia - tiny red spots (platelets) Purpura - purple-ish bruises (platelets) Ecchymoses - large bruises (platelets) Shortness of Breath (RBC) Bruising (platelets) Jaundice (RBC)
Erythrocyte Disorders
Result when numbers are either excessive or inadequate - a balance must exist between production and destruction
Erythropoiesis
Production of RBC’s (formed in red bone marrow - myeloid tissue)
Hemocytoblasts differentiate into erythrocytes under the influence of the hormone EPO (erythropoietin) released from the liver or kidneys
Abundance of reticulocytes = red bone marrow working hard
Reticulocytes
Immature Red Blood Cells
RBC Destruction
RBC’s live 120 days before becoming fragile and inflexible. They are destroyed in the liver and spleen
Fate of RBC Components
Heme-
- Fe+ - keep in body
- Pigment - get ride of (if backs up = jaundice)
Globin-
-Amino Acids (recycled - kept in body)
Polycythemia
Elevated number of RBC’s
Primary Polycythemia
Increase in RBC’s due to hyperactivity of the myeloid tissue
- Example: Polycythemia Vera - idiopathic, (genetic mutation?)
- Signs and symptoms include: hyper viscosity, sluggish flow, and thrombosis
Secondary Polycythemia
Increase in RBC’s due to an increase in demand for oxygen
- Examples: smokers (decrease oxygen, so EP increases), altitude (kidneys don’t receive enough oxygen so kicks up EPO)
- Due to artificial or natural increase in EPO (EPO dependent)
Anemia
Lower than normal oxygen capacity of the blood
Condition, not a disease, of RBC or hemoglobin deficiency
Etiology (anemia)
- <Hb (do not have hemoglobin)
Categories of Anemia
- Deficiencies
- Problems with the bone marrow
- Hemolytic
Anemia - Fe deficiency
- Hemorrhagic due to chronic blood loss
- menorrhagia, ulcers, CA - Insufficient dietary intake
- Pregnancy
May see hypochromic cells (pale RBC’s) or microcytic cells (smaller than normal RBC’s)
Anemia - Vitamin B12 Deficiency
Due to inadequate diet (nutritional) or inability to absorb vitamin B12
May see macrocytic/megablastic (really big) or normochromic (normal color)
Problems with Bone Marrow
Aplastic - due to defect in the red bone marrow resulting in a decrease in stem cell population, due to radiation, chemicals, toxins, chemotherapy, or idiopathic. Or autoimmune.
Results in pancytopenia - all formed elements decreased (biggest concern = opportunistic infections)
Best Treatment = bone marrow transport
Pernicious Anemia
Lack of gastric intrinsic factor for absorption
“deadly”
(cannot absorb Vitamin B12 from body)
Treatment - Vitamin B12 injections to bypass gastric
Hemolytic
Rapid destruction of RBC’s due to genetic defect, immune destruction, or mechanical forces
(mechanical forces - generally someone on heart/lung machine or constant pounding on foot = destroyed RBC. Example = army marching and runners)
Two Examples:
- Sickle Cell Anemia
- Erythroblastosis Fetalis
Sickle Cell Anemia
Inherited Disorder = defective hemoglobin (Hb)
Incidence
- 50,000 black Americans affected
- 1 in 12 are carriers in US
- 1 in 3 are carriers in Africa
Sickle Cell Anemia Description
A single amino acid substitution results in deformed hemoglobin causing the RBC to sickle when deoxygenated. The deformed RBC obstructs blood flow in microcirculation causing occlusion and tissue hypoxia.
Sickle Cell Anemia Etiology
Genetic - Autosomal Recessive Gene Disorder
Sickle Cell and Malaria
If a person is heterozygous for sickle cell (sickle cell trait) they are protected from malaria and they do not have severe symptoms of sickle cell anemia. Thus this genetic mutation has been favored (a case of balancing selection).
(mutation that was selected)
Signs and Symptoms (Sickle Cell Anemia)
Sickle Cell Crisis
Sickle Cell Crisis Induced by:
Exertion (RBC’s live 20 days), Illness, hypoxia, acidosis, dehydration.
People have severe anemia pain (from vessel obstruction) organ damage, and hyperbilirubinemia (too much bilirubin in blood)
(will have infarctions because of cells sticking)
Sickle Cell Anemia Treatment
No cure unless bone marrow transplant works.
Prevent vasocclusive crisis - hydroxyurea and EPO’s, bone marrow transplant
Sickle Cell Anemia Prognosis
50% survive until 50
Erythroblastosis Fetalis
Another type of hemolytic anemia
If mother who is Rh- but sensitized (has anti-Rh antibody) becomes pregnant with Rh+ baby = agglutination
(Never opposite)
Erythroblastosis Fetalis Prevention
RhoGAM - binds with fetal antigens in mom before antibodies can be produced
(prevents sensitization)
Leukocytosis
Over 10,000 WBC’s present indicates infection
Leukopenia
White cell depletion
Usually involves neutrophils
(Normal count is 4-7,200)
Fewer than 1,800 means increased risk of opportunistic infections
Leukemia
Primary malignant tumors of the leukocyte precursors in the marrow
Do not produce tumor masses
Disseminated CA (released in blood and cells travel throughout the body)
General Pathogenesis and Signs and Symptoms of Leukemia
Rapid proliferation of non-functional WBC’s
- spill into blood
- infiltrate organs
Signs and Symptoms
- fatigue (anemia; WBC’s take up space)
- infection (WBC’s not functioning)
- bleeding (decrease in platelets)
- pain (infiltrating organs; bone marrow very active and expanding; necrosis of bone
Stem Cell Harvest
- Extract directly from bone
- Extract from blood-peripheral blood stem cell harvest
- Give G-CSF (granulocyte - colony stimulating factor)
- -causes bone marrow to become active and release in blood
Types of Bone Marrow Transplants
- Allogenic - 1 patient and 1 donor match MHCs/HLAs
- two people, may have rejection
- best chance for a cure IF there is a good match - Autologous - patient and donor are same = no rejection
- cleans out bone marrow and injects healthy cells back into blood
Albumins
Plasma Protein
Made by liver
Function: maintain osmotic pressure in blood (“sucking” fluid toward blood vessel)
Hypoalbuminemia
“not enough albumin in blood”
= ascites
Ascites
Abnormal accumulation of fluid in the abdominal cavity
Seen in: starvation, cirrhosis, kidney
Platelets Function
Repair slightly damaged blood vessels and initiate the clotting reaction
Thrombocytopenia
Decreased number of circulating platelets
For symptoms to occur = 10,000-20,000/mL
(Normal Range = 150,000-400,000/mL of blood)
Number must be REALLY low for symptoms
Etiology of Thrombocytopenia
- Decreased production
- -In malignancy (ex leukemia) normal marrow cells are replaced with malignant cells impairing platelet synthesis
- -suppression of bone marrow activity (radiation, meds)
- -aplastic anemia (defective bone marrow) - Increased pooling in the spleen
- Decreased survival/lifespan of platelets.
–can result from an autoimmune response following a viral illness, certain medications, or be idiopathic
(most are idiopathic)
Splenomegaly
Enlarged spleen
Up to 80% of platelets may be contained in the spleen
1/3 platelets held in spleen normally
Idiopathic Thrombocytopenia Purpura
Auto Ab formation against platelets = petechiae and purpura
(most often occurs after viral infection)
(most often in kids <5 years old)
Goes away on its own - no treatment needed - no sequela
