MHD Lecture 6 & 7 - Circulation & Neoplasia I Flashcards
Hypermia & Congestion both refer to what?
Which one is described by the following:
- Active process
- state an example - Tissues appear “redder”
ex: inflammation
- excercising skeletal muscle
Which one is:
- Passive
- state an example - Systemic process (CHF) vs isolated process (deep vein thrombosis)
- Acute vs Chronic
- Tissues have abnormal “red-blue” color (since associated with venous blood)
- increased intravascular blood volume
in tissue, an organ, or body part - Hyperemia
ex: arteriolar dilation & increase blood flow (rubor)
CONGESTION:
passive –> impaired outflow of venous blood from tissue
(veins do not dilate because of the active influence of a sympathetic discharge or chemical mediator)
How does hepatic congestion result due to CHF?
systolic dysfunction
- poor pumping of heart, right side starts to get weak and blood cannot pump so there is a back flow of blood = pooling of blood in the liver (HEPATIC CONGESTION)
What is:
A series of regulated processes that
a) maintain blood in a fluid clot-free state in normal vessels
&
b) rapidly form a localized hemostatic plug at the site of vascular injury
HEMOSTASIS
_____ is Flow of blood from a ruptured blood vessel
Blood may flow into tissue, into a body cavity (pleura, pericardia, peritoneal space, join space) or outside the body.
Why?
Hemorrhage
WHY?
- stabbed/lacerated
- Congested leading to focal hemorrhage
- Aortic aneurism (aorta starts to bulge)
What are 2 ways a hemorrhage can form?
What is the only clinical correlation in which hemorrhage is NORMAL?
What does seriousness depend on?
Bleeding occurs when large or small blood vessel is disrupted by:
- mechanical force
- pathologic process
(congestion, inflammation, neoplastic erosion of vessel, ROS –> lead to DNA damage)
**Abnormal hemostasis causes a predisposition to bleeding
- MENSTRUAL BLEEDING
- Seriousness depends on site as well as rate/amount of blood loss
(intracerebral hemorrhage vs. subcutaneous hematoma)
____ is the result of movement of fluid from vasculature into interstitial spaces or body cavities.
Accumulation of abnormal amounts of fluid in interstitial spaces or body cavities.
EDEMA
- normally prevented by balance between hydrostatic & plasma oncotic pressure & take up by lymphatics
What are 5 causes of edema?
Can you name some examples that might cause these?
- Increased hydrostatic pressure
-CHF
Local = impaired venous return post DVT - Decrease colloid osmotic pressure, due to reduced plasma albumin
- hypoalbuminemia
- liver disease
- malnutrition
- nephrotic syndrome = increased loss - Lymphatic obstruction
- neoplasm - Increased vascular permeability
* *inflammation** - Sodium Retention
- Renal failure
(retaining sodium & pulling fluid in which overwhelms the circulature)
What is an example of a state of malnutrition that causes full body edema?
Kwashiorkor
Malnutrition, liver disease, and nephrotic syndrome all lead to decreased ______
Heart failure leads to:
- plasma albumin
- a) increased capillary hydrostatic pressure
b) decreased renal blood flow & thus renin-ATII system active
= EDEMA
What is the difference between exudate & transudate?
exudate:
- high protein content
- white & red cells
- *vasodilation**
transudate:
- low protein content
- few cells
- CHF, venous outflow obstruction
- decreased plasma oncotic pressure due to liver disease, kidney disease (loss of protein)
Define the following:
Formation of blood clot within an intact vessel.
Is this always a pathologic process?
Thrombosis
- yes
What are the 3 key elements of hemostatic processes?
- Vascular Wall – endothelial cells must be intact
- Platelets
- Coagulation Cascade
What are 3 mechanisms of thrombosis?
- Endothelial injury
ex: inflammation
- advanced atherosclerosis
- Altered blood flow:
Clinical examples:
a) turbulence (atherosclerotic vessel narrowing)
b) stasis (atrial fibrillation - not pumping regularly due to conduction abnormality)
- Hypercoagulable state:
- Predisposition to easy clot formation
Clinical examples:
Inherited: Protein C deficiency
Acquired: woman who smokes and uses oral contraceptives; disseminated cancer
What is the most important factor in Virchow’s triad in thrombosis?
endothelial integrity!!!
What are the fates of a VENOUS thrombus? (4)
- Resolution
- Embolization to lungs
- Organization
- incorporated into the blood vessel - Organized & recantized
- new blood vessels
What is an embolism?
What are the 4 types?
Intravascular substance (solid, liquid, gas) which is carried by blood from point of origin to distant site.
- Fragments of thrombi
(thromboembolism) - Amniotic fluid
- Amniotic fluid enters placental membranes and/or uterine vein rupture. - Air (gas)
- medical procedures like air trapped during bypass surgery, or cerebral artery during near surgery - Fat & Marrow embolism
- soft tissue crush injury where marrow vascular sinusoid releases microscopic fat globules
- severe trauma to bone
Embolus derived from a lower-extremity deep venous thrombus lodged in a
pulmonary artery branch is called___
Saddle pulmonary embolism
56-year old woman develops a popliteal venous thrombosis after hip replacement surgery. She recovers and returns to her job as a teacher. Three months later, which of the following term would describe the process mostly likely seen in the popliteal vein? A. Acute inflammation B. Granulomatous inflammation C. Embolization D. Organization (at 3 month mark) E. Propagation
D. organization
_____ is an area of ischemic necrosis (cell death as result of cell injury) caused by occlusion of vascular supply to affected tissue
Infarction
-Majority of infarcts are associated with thromboembolism and involve arterial occlusions.
Which type of infarct is the following:
- Arterial occlusion
- Solid organ with end-arterial circulation (not dual)
- Heart, liver, spleen, kidney
- Ischemic
WHITE (pale) infarct
What are the 4 things associated with red infarcts?
- Venous occlusions
- Ovarian torsion - Tissues with dual circulations
- Lung - Loose tissues
Lung*** = air spaces, not very solid
- When flow re-established after infarction
- S/p angioplasty of arterial obstruction
What is characterized by systemic hypo perfusion with resultant
- impaired tissue perfusion
- cellular hypoxia
Shock
Can be caused by diminished cardiac output or by reduced effective circulating blood volume
What are the 3 major types of shock?
- Cardiogenic
- low C.O. output due to myocardial pump failure - Hypovolemic
- low C.O. due to loss of blood or plasma volume - Septic
- vasodilation and venous blood pooling from microbial infection
A 65-year old previously healthy man is hospitalized for bilateral pneumonia. On hospital day #8 he is found to have swelling and tenderness of his left leg. An ultrasound examination reveals findings consistent with acute left common femoral vein thrombus. Which of the following conditions is most likely to have contributed the most to this finding? A. Protein C deficiency B. Prolonged immobilization C. Hypertension D. Left ventricle mural thrombus E. Chronic alcohol use
B) prolonged immobilizaton
On sectioning of an organ from a 69-year old woman at the time of autopsy, a focal wedge-shaped area that is firm is accompanied by extensive hemorrhage, giving it a red appearance. The lesion has a base on the surface of the organ. In which of the following situations did this lesion most likely develop? A. Spleen with embolized mural thrombus B. Kidney with septic embolus C. Liver with hypovolemic shock D. Heart with coronary thrombosis E. Lung with pulmonary thromboembolism
E) lung with thromboembolism
Define:
Neoplasia
Tumor
- New monoclonal growth
- Disorder of cell growth
- triggered by series of acquired mutations of single cell & its clones
What are 2 basic components of all tumors?
- Parenchyma
- neuroectodermal, epithelial, or mesenchymal in origin - Stroma
- connective tissue, blood vessels, immune system cells
- support growth and spread of neoplasm
What is the immune peroxidase stain?
Immuno peroxidase stein
- antibody for antigen colored with peroxidase stain so appears brown
Rare tumors containing cells from more than one germ layer are called ____
Teratomas
What mesenchymal tissues only have malignant parenchymal cell types?
Lymphoid tissue (lymphoma)
Hematopoietic Cells
leukemia
What are “mixed tumors” that are derived from 1 germ cell layer?
example?
Single neoplastic clone capable of divergent differentiation
- Derived from 1 germ cell layer
- More than 1 neoplastic cell type
SALIVARY GLAND:
- clone capable of epithelial & myoepithelial differentiation
(still of one germ cell layer, but one clone took a divergent path)
PLEOMORPHIC ADENOMA
- neoplastic epithelial cells scattered in neoplastic mixed stroma
What type of cells make up epithelium?
Stratified squamous cells
Epithelial lining of glands of ducts
adenoma, adenocarcinoma
What are teratomas?
Totipotential germ cells that differentiate into any cells in th body
-neoplasms originate in gonads, abnormal midline embryonic rests
name some mixed tumors
Derived from one germ cell layer:
Salivary glands
Derived from more than one germ layer:
Gonads –> totipotential germ cells
= teratoma if benign
immature teratoma, teratocarcinoma
The following tissues are of what origin: fibrous tissue chondroid osteoid blood vessels smooth muscle skeletal muscle
MESENCHYME
What are some characteristics of malignant neoplasms?
3 most important?
Well-differentiated to very de-differentiated (anaplastic)
Pleomorphic (variation in nuclear size and shape)
Abnormal nuclear morphology
- High N/C ratio (1: 1 )
- Hyperchromatic
- Prominent nucleoli
Mitoses *
How is anaplastic tissue defined?
- High N:C ratio
- Prominent nucleoli
- Pleomorphic
If a keratin pearl is present, what type of cell is this?
Squamous cell!
Dysplasia is_____
Principally found in ____
What characteristics?
What does one unique aspect that demarcates it from BENIGN tumors?
What is the normal N: C ratio?
Are they reversible?
“disordered growth”
EPITHELIUM
- pleomorphism
- Hyperchromatic nuclei
- High N/C ratio
- Mitotic figures above basal layer!!!
- Disorderly maturation
DOES NOT PENETRATE THE BASEMENT MEMBRANE
Nuclear to cytoplasmic ratio (N:C ratio) – normal cells generally have a N:C ratio of 1:4 or 1:6. This ratio may approach 1:1 in malignant cells
__ yes reversible, if factors can be removed
When dysplastic cells involve the entire THICKNESS of an epithelial surface, it is referred to as _____
carcinoma in situ (“preinvasive cancer”)
What is anaplasia?
What is seen histologically?
Anaplasia – “backward differentiation” – loss of the structural and functional differentiation of the cells from which a neoplasm is derived
- failure of normal differentiation
- marked nuclear and cellular pleomorphism
- numerous mitotic figures extending toward
the surface
BASEMENT MEMBRANE INTACT
Which are reversible:
dysplasia or anaplasia?
If the full thickness of squamous has been invaded, but the basement membrane is intact is this dysplasia or anaplasia?
DYSPLASIA
- precursor to malignancy
** DYSPLASIA*
Squamous Carcinoma In-Situ
- no tumor in sub epithelial stroma, BM intact
What is a squamous cell carcinoma?
What is metaplasia?
Invasion of malignant cells into STROMA
- past BM
–>a cell that has adapted by changing their cell type (columnar to squamous cell CERVIX & the LUNG)
can revert back to normal cells!
What are 3 pathways of dissemination of metastasis ?
Which is most typical of carcinomas?
Which is more typical of sarcomas?
- Seeding within natural body cavities
- Lymphatic spread
- more typical of carcinomas (epithelial) - Hematogenous spread
* typical of sarcomas (mesenchyme)
Cancer is the ____leading cause of death in the US
What cancer have we essentially wiped out due to screening?
2nd
have essentially wiped out squamous cell carcinoma due to screening PAP SMEAR
(so mortality rate for cervical cancer has decreased)
What are carcinogens?
_____: Major cause of preventable deaths in US
LUNG, upper airway, bladder, pancreas, kidney, and esophagus
Agents that damage DNA increasing the risk for cancer
Tobacco
+alcohol
What is a huge US epidemic?
Proposed mechanisms?
obesity
- many cancers associated with it
- Elevated insulin levels (elevated growth factors)
- Increased estrogens
- Decreased adiponectin
- Proinflammatory state
What are some occupational exposures that could lead to cancer?
- lung cancer
- Bladder cancer
- Mesothelioma, lung cancer
- Polycyclic hydrocarbons in COAL
- tar, mineral oils, car exhaust - Aromatic amines and azo dyes in dye & rubber industry
- Asbestos exposure in construction, ship building
- sunlight, radiation, sexual exposures
Most cancers in ____ years old
what are most common?
> 55
carcinomas
cancer accounts for more than 10% of deaths in children
What are some hereditary variables involved in cancer for the following:
- Autosomal dominant cancer syndromes
(2) - Autosomal recessive (1)
- Familial Cancers of uncertain inheritance
- Familial adenomatous polyps of colon: nearly 100% develop colon cancer (benign neoplasms– > become dysplastic –> become dysplastic in situ –> carcinoma)
- Familial retinoblastoma:
100,000 times risk of cancer than in general population
RECESSIVE:
1. Xeroderma Pigmentosum
Uncertain inheritance:
1. Evident familial clustering (colon, breast, ovary, brain)
- Pattern inheritance unclear
What are 3 acquired predisposing conditions to cancer?
How?
1.Chronic Inflammation
- chronic tissue injury
- -> due to ROS which leads to DNA damage and metaplasia
- Precursor Lesions
Barrett esophagus, squamous metaplasia of bronchus, endometrial hyperplasia
- Immunodeficiency
- particularly T cells
