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Natural History of Disease
Review
75
Medical
Professional
08/06/2011

Additional Medical Flashcards

 


 

Cards

Term
What is incidence rate?
Definition
the number of newcases per unit of population per unit of time
Term
What is prevalence rate?
Definition
the total number of cases per unit of population at a given time
Term
What is mortality rate?
Definition
the number of deaths per unit of population per unit of time
Term
What are the stages of most diseases?
Definition
  1. Susceptibility
  2. Asymptomatic disease
  3. Clinical Disease
  4. Disability
Term
What is susceptibility?
Definition

The stage of a disease where pathologic changes are not detectable but risk factors are


Note: primary prevention is relevant

Term
What is asymptomatic disease?
Definition

stage of a disease where symptoms have not appeared but pathologic changes or indicators are detectable


Note: secondary prevention/early intervention is relevant

Term
What is clinical disease?
Definition

The stage of a disease where symptoms have appeared and a diagnosis is possible if a physician is consulted. The patient may or may not be significantly disabled, depending on the patient


Note: interventions resulting in iatrogenic disease must be prevented

Term
What is disability?
Definition

The significant phase of disease in which it interferes with the performance of one or more of the patient’s valued roles


Note: Tertiary prevention ( control of disability and rehabilitation) is relevant

Term
What is the root of atherosclerosis?
Definition

athere = "gruel” referring to the lipid accumulation

sclerosis = “hardening” referring to the thickening of the arterial intima

Term
Describe the growth of atherosclerotic plaques?
Definition
does not occur in a smooth linear fashion, but rather discontinuously, with periods of relative quiescence interrupted with periods of rapid evolution occurring over a period of many years, usually many decades
Term
Areas of the Circulatory System and Corresponding Clinical Syndromes in Atherosclerosis
Definition

 

Coronary arteries – angina pectoris, myocardial infarction
Arteries to the CNS – transient ischemic attack, stroke
Peripheral circulation – intermittent claudication, gangrene
Splanchnic circulation – mesenteric ischemia, bowel infarction
Renal circulation – renal artery stenosis, secondary hypertension and atheroembolic disease

 

Term
Typical regions of atherosclerosis formation (usually focally, sparring adjacent regions)
Definition
Coronary arteries – proximal LAD
Arteries to the CNS – carotid bifurcation
Renal circulation – proximal portions of the renal arteries
Term
Where do lesions of atherosclerosis occur?
Definition
at branch points of arteries, which are regions of disturbed blood flow, suggesting that local fluid dynamic factors may contribute to the focal distribution of lesions
Term
What can atherosclerotic lesion cause?
Definition
stenosis (causing flow limitation), arterial occlusion, ectasia/aneurysm (dilation) that can cause ruture or dissection
Term
What are chronic expressions of atherosclerosis?
Definition
angina pectoris, intermittent claudication, mesenteric ischemia
Term
What are the acute events of atherosclerosis?
Definition
MI, sudden cardiac death, CVA, bowel infarction
Term
What are the 3 layers of artery wall?
Definition
intima, media, adventitia
Term
Describe arterial intima layer
Definition
lined with a monolayer of endothelial cells in contact with the blood that are embedded in extracellular matrix
Term
Describe arterial media layer
Definition
layers of smooth muscle cells that are invested with collagen- and elastin–rich extracellular matrix that are separated from the intima by the internal elastic membrane
Term
Describe arterial adventitia layer
Definition
contains the nerve fibers and small vessels (vasavasorum) that supply blood to the arterial wall
Term
Describe healthy endothelium
Definition
Tight cobblestone sheath that controls the passage of substances from the plasma to the underlying artery wall by specific transport mechanisms;

also secretes substances like prostacyclin that inhibits platelet aggregation and   Factor VIII that is necessary for clotting

Term
What initiates atherosclerosis?
Definition

insult to the endothelium that initiates plaque buildup.

Insult can be due to metabolic, mechanical or immunologic

 

This causes loss of endothelial cells to function normally, or to attach to each other, or to attach to underlying connective tissue

Term
What is fatty streak?
Definition
initial lesion of atherosclerosis where there is an accumulation of lipoprotein particles in the intimal layer of the artery, where they bind to constituents of the extracellular matrix (usually proteoglycan)
Term
Two ways lipoprotein attachem to ECM is modified
Definition
lipoprotein oxidation and nonenzymatic glycation
Term
What is lipoprotein oxidation?
Definition
Both the lipid and the protein moieties of the LDL particles participate in oxidative modification.
Lipid moieties are changed to hydroperoxides, lysophospholipids, oxysterols and aldehydic breakdown products of fatty acids.
The apoprotein changes include breaks in the peptide backbone and in the derivatization of certain amino acids residues
Term
What is nonenzymatic glycation?
Definition
in sustained hyperglycemia (diabetes) nonenzymaticglycation of apolipoproteins and other arterial proteins likely occurs that may alter their function and their propensity to accelerate atherogenesis
Term
The second step of fatty streak formation?
Definition
Recruitment of leukocites, especially mononuclear cells (monocytes and lymphocytes)
Term
What are ICAM1, VCAM1, P selectin?
Definition
receptors for leukocytes on the surface of endothelial cells
Term
What is Lysophosphatidylcholine
Definition
A constituent of oxidatively modified LDL that can augment expression of VCAM-1
Illustrates the link between the accumulation of lipoproteins in the intima with leukocyte recruitment
Term

How can hemodynamic forces influence the cellular events that initiate atherosclerotic lesions and explain their focal distribution at certain sites predetermined by altered blood flow

Definition
Ordered laminar shear of normal blood flow augments the production of NO by the endothelium, which has vasodilator properties and, at low levels produced by the arterial endothelium, can act as a local anti-inflammatory, limiting VCAM-1 expression.

Sites of predilection for forming atherosclerotic lesions, e.g. branch points, often have disturbed laminar flow and are unable to suppress VCAM-1 expression

Term
What role do cytokines play in atherosclerosis?
Definition
Since  modified lipoproteins can induce cytokine release from vascular wall cells, IL-1 or TNF-α can induce or augment the expression of VCAM-1 and ICAM-1 on endothelial cells.


Term
What is the 3rd step of atherosclerosis?
Definition
After the interaction leukocytes and endothelial cell receptor, the monocytes and lymphocytes penetrate the endothelial layer and take up residence in the intima. This migration may result from the action of oxidized LDL which may promote the chemotaxis of leukocytes
Term
What is the fourth step of atherosclerosis?
Definition
mononuclear phagocytes differentiate into macrophages and transform into lipid-laden foam cells after uptake of lipoprotein particles by receptor mediated endocytosis
Term
What is the 5th step of atherosclerosis?
Definition
 
 
 
 
 
 
 
Some lipid-loaded macrophages may leave the artery wall to clear lipid from the artery.
 
Some lipid-loaded foam cells within the expanding intimal lesion will perish; some of the cell death may result from apoptosis and result in the necrotic core of an atherosclerotic plaque.

Lipid accumulation and the propensity to form atheroma will ensue if the amount of lipid entering the artery wall exceeds that exported by mononuclear cells or other pathways

Term

What is the 6th step of atherosclerosis?

Definition

Formation of fibrous cap and lipid core:

Macrophages loaded with modified lipoproteins, like intrinsic vascular wall cells, may elaborate cytokines and growth factors that can stimulate smooth muscle cell proliferation and production of extracellular matrix

 

IL-1 and TNF-α in plaques can induce local production of growth factors like Platelet derived growth factor and Fibroblast growth factor

 

IFN γ from activated T-cells within lesions,  can inhibit smooth cell proliferation and synthesis of interstitial forms of collagen.
Reactive oxygen species can modulate growth of smooth muscle cells, activate inflammatory gene expression and annihilate NO radicals, decreasing the effect of this endogenous vasodilator
macrophage may be activated to express the inducible form of the enzyme that can synthesize NO and produce relatively large cytotoxic amounts of NO radicals (low level is beneficial; overproduction is deleterious) 
Term
What are ways to remove lipid from atheroma?
Definition
Export by phagocytes and reverse cholesterol transport mediated by HDL
Term
What other factors can modulate atherogenesis?
Definition
Male gender and postmenopausal state, diabetes mellitus, hypertension, Lp(a) (apoprotein (a) molecule bound to apolipoprotein B moiety of LDL. Apoprotein (a) has homology with plasminogen which may inhibit fibrinolysis by competing with plasminogen), homocysteinemia (promote thrombosis), tobacco, antecedent inflammatory states, viral and microbial pathogens, immune/autoimmune reactions
Term
fatty streak commonly precedes the development of more advanced atherosclerotic plaque, but do all fatty streaks progress to yield atheroma?
Definition

No, not all the time. The lipid in the fatty streak is mainly  cholesterol oleate. It is usually sessile and causes no obstruction or symptoms 

 
Term
When is fatty streak 1st present in people?
Definition
It is present in the aorta by age 10.  It increases to occupy 30-50% of the aortic surface by age 25. It does not appear to extend further by aging.
In coronary arteries, fatty streaks are usually observed by age 15 and involve more area with increasing age; they may be an indicator of clinically raised lesions later in life.
In cerebral arteries, fatty streaks develop during the 3rd and 4th decades               
 
 
 
 
 
 
 
 
Term

True or False?

Arrival of smooth muscle cells and their elaboration of extracellular matrix probably provides a critical transition, yielding a fibrofatty lesion in place of a simple accumulation of macrophage derived foam cells

Definition
True
Term
What is the 7th step of atherosclerosis?
Definition

Rupture of plaque and cause thrombus. In advanced fatty streaks, microscopic breaches in endothelial integrity may occur. Microthrombi rich in platelets can form at such sites of limited endothelial denudation, due to exposure of the highly thrombogenic extracellular matrix of underlying basement membrane  

Activated platelets release numerous factors that can promote the fibrotic response and alter smooth muscle function.

Most microthrombi resolve without clinical manifestation by a process of local fibrinolysis, resorption and endothelial repair

 

 

 

 

 

 

Term
What are fibrous plaques?
Definition

palpably elevated areas of intimal thickening and are the most characteristic lesion of advancing atherosclerosis          

 

 

 

consist of a central core of extracellular lipid and necrotic cell debris covered by a fibromuscular layer.
The plaque is much thicker than is the normal intima and is mainly cholesterol ester.
The principal esterified fatty acid is linoleic acid rather than oleic acid.

Plaque cholesterol ester composition differs from fatty streaks but resembles plasma lipoproteins                       

 

 

 

 

 

 

 

Term
When do fibrous plaques appear?
Definition
appear in men before women and in the aorta before the coronary arteries and much later in the vertebral and intracranial cerebral arteries
Term
What are other advances of atherosclerosis?
Definition

Hemorrhage and Calcium Deposit:

As atherosclerotic lesions advance, abundant plexi of microvessels develop in connection with the artery’s vasavasorum.
These microvascular networks may contribute to complications of the atheromatous plaque by providing surface area for leukocyte trafficking to and from the atheroma, and furnishing a foci for intraplaque hemorrhage.

Atherosclerotic plaques also accumulate calcium. Proteins specializing in binding of calcium, such as osteocalcin, osteopontin and bone morphogenetic proteins, also occur in atherosclerotic lesions  

During the initial phases of atheroma development, the plaque usually grows outward in an abluminal direction.
The growing atheroma does not encroach on the arterial lumen until the burden of atherosclerotic plaque exceeds approximately 40% of the area encompassed by the internal elastic lamina.

With increasing necrosis and accumulation of extracellular lipid, the arterial wall progressively weakens and ruptures of the intima can occur, causing aneurysm and hemorrhage 

Arterial emboli can form when fragments of plaque dislodge into the lumen.
Thrombosis occurring on top of an atherosclerotic plaque further decreases the size of the arterial lumen.
Flow limiting stenosis and impaired organ function result from gradual occlusion as plaques thicken and thrombi form.

The hypoxic stimulus of repeated bouts of ischemia characteristically induces the formation of collateral vessels, such as the coronary arteries  

 

 

 

Term
The percentage of coronary artery luminal stenosis that must occur before a patient develops symptoms of coronary disease?
Definition
Up to 60-70%. 
Term
What is the first sign of CAD
Definition
Acute MI, 25% are usually fatal.
Term
The minority with the highest age-adjusted heart disease death ratio (minority/non-Hispanic white) is
Definition
African American
Term

In addition to modified lipoproteins, what other factors can regulate the expression of adhesion molecules for leukocyte recruitment in fatty streaks?

Definition
Il-1 and TNF-alpha
Term
What are the risk factors for lung carcinoma?
Definition
Tobacco (90%), asbestosis, air pollution, pitchblend / radon, metals (nickel and silver mostly), chemical products
Term
What are the different types of lung carcinoma?
Definition
Squamous cell carcinoma, Small cell carcinoma (Oat cell) (Note: these 2 types have lesion in center of CXR)
AdenocarcinomaLarge cell carcinoma
Other – epidermoid, carcinoid, bronchial gland tumors, and mesotheliomas
Term
What are the symptoms of lung carcinoma
Definition
Change in pulmonary habits, Cough, chest pain, rust-streaked sputum, purulent sputum, hemoptysis, dyspnea
Local complications – superior vena cava obstruction, shoulder / arm pain, recurring pneumonitis or pleural effusions, CHF or arrhythmias, hoarseness
Extra-pulmonary manifestations – endocrine, neuropathy / myopathy, skin rashes, clubbing of fingers, migratory thrombophlebitis, anemia initial metastatic presentation
Term
What are the risk factors of breast carcinoma?
Definition
Gender
Age
Geographic location
Prior radiation
Benign breast disease – atypical hyperplasia, sclerosingadenosis
Exogenous hormone usage – HRT
Menarche before age 12, menopause after 50, first pregnancy after age 30 or nulliparity
Previous history of breast cancer
Family history of breast cancer in a sister, mother, or daughter
Family history of  BRCA-1, BRCA-2, Li-Fraumeni syndrome
Other – high socioeconomic class, high dietary fat intake
Term
What are the types of breast carcinoma?
Definition
Invasive ductal – more than 80%
Infiltrating lobular – approximately 10%
Medullary – 5%
Other – papillary, mucous, squamous cell, Paget’s disease, sarcomas, carcinosarcoma
Term
What are the symptoms of breast carcinoma?
Definition
painless lump or mass, skin dimpling, nipple retraction, bleeding from the nipple, reddening of the skin, ulceration, pain, fixation to the chest wall, enlarged axillary nodes
Term
Where is the breast carcinoma usually found?
Definition

Upper outer quadrant – 50%

  Central portion – 20%

  Medial quadrants – 20%

  Lower outer quadrant – 10%

Term
What is the least sensitive screening method of breast carcinoma?
Definition

Breast Self Examination

 

Overall sensitivity in the BCDDP trial was 26%
Most sensitive (41%) for women 35-39
Least sensitive (21%) for women 60-74
Term
What are the prognosis (prediction) of breast carcinoma?
Definition
Stage of the disease
Node positivity
Estrogen and progesterone  receptor positivity
Measures of tumor growth rate (flow cytometry)
Histologic classification (nuclear grade)
Molecular changes in the tumor (HER-2/neu)
Term
What is the second most common cancer in US for male and female?
Definition

Colorectal cancer

Note: Second highest mortality for both male and female in US

Term
What are the risk factors of colorectal cancer?
Definition
Personal history of adenomatous polyps
Personal history of ulcerative colitis
Personal or family history of polyposis coli (familial adenomatouspolyposis of the colon) or of hereditary nonpolyposis colon cancer (HNPCC or Lynch syndrome)
Personal or family history of colorectal cancer
Ureterosigmoidostomy
Streptococcus bovisbacteremia
Other – increased dietary fat, decreased dietary fiber
Term
What are the symptoms of colorectal carcinoma?
Definition
Right colonic lesions with unexplained iron-deficiency anemia and GI tract bleeding, asymptomatic abdominal mass, tumor obstruction in the ileocecal valve (rare) producing a small bowel obstruction.

Sigmoid colon tumor present with obstruction from circumferential growth and gross blood per rectum observes


Tumors in the rectum exhibit rectal pain, gross blood per rectum, tenesmus with a feeling of incomplete rectal evacuation

 

Term
Where are colorectal carcinoma usually found?
Definition
-Cecum and ascending colon – 16%
-Transverse colon – 8%
-Descending colon – 6%
-Sigmoid colon – 20%
-Rectum - 50%
Term
What are the prognosis of colorectal carcinoma?
Definition
Depth of tumor penetration into the bowel wall
Presence of regional lymph node involvement
Presence of distant metastasis
Term
What is the most common cancer in male in US
Definition
Prostate cancer
Term
What are the risk factors of prostate carcinoma?
Definition
Age
Race
Family history
Environmental factors ?
Term
What are the types of prostate carcinoma?
Definition

Adenocarcinoma 

Other – squamous cell and transitional cell
Term
What are the symptoms of prostate carcinoma?
Definition
Earlysymptomaticobstruction – difficulty starting the urinary stream, unexplained cystitis / dysuria, hematuria, and dribbling.
Advancedsymptomaticpresentation – bladder outlet obstruction symptoms with urinary retention, ureteral obstruction with anuria, azotemia, anorexia or bone pain from bony metastatic disease.
Earlydetection - finding a small asymptomatic nodule on rectal examination or finding an unsuspected carcinoma in a surgical specimen after a TURP for benign prostatic hypertrophy
Term
What is the prognosis for prostate carcinoma?
Definition
Local extension beyond the capsule rarely produces symptoms.
Between 35 – 75% of the patients have metastatic disease to the surrounding lymph nodes or bone at the time of diagnosis.
In addition to the stage of the disease at the time of diagnosis, the prognosis is also determined by the grading of the tumor.
Term
What is the ACS recommendation for Breast Cancer for early detection?
Definition

Breast self exam – starting in the early 20s

Clinical breast exam – every 3 yrs, ages 20-39

       annually, starting at age 40*

  Mammography – annually, starting at age 40

Term

What is the ACS recommendation for Colorectal Cancer for early detection?

Definition

For men and women over age 50:

 

  Flexible Sigmoidoscopy – every 5 years, starting at age 50

  FOBT or FIT           -   annually, starting at age 50 

  Colonoscopy            -  every 10 years, starting age 50

  Double Contrast Barium Enema – every 5 years, starting at age 50  

  Computed Tomography Colonography – every 5 years, starting age 50

 

Term

What is the ACS recommendation for Prostate Cancer for early detection?

Definition

Digital rectal exam (DRE) and PSA annually

Term

What is the ACS recommendation for Cervical Cancer for early detection?

Definition

 

 

 

 

 

 

 

 

 

For women 18+

Pap test should begin app. 3 yrs after a woman begins having intercourse, but no later than age 21.

Screening should be done every year with conventional Pap tests or every 2 yrs using liquid-based Pap tests.

At or after age 30, women who have had 3 normal Paps in a row may get screened every 2 to 3 yrs.

Women age 70 and older who have had 3 or more normal Paps and no abnormal Paps in the last 10 yrs and women who have had a total hysterectomy may choose to stop cervical cancer screening

Term

What is the ACS recommendation for  for early detection in people with average risk and asymptomatic?

Definition
For men and women age 20+, every 3 years from ages 20 to 39 years and annually after age 40
Term

Incidence rates and death rates for prostate cancer are much higher in which of the following minorities?

Definition
African American
Term
The most likely location for a breast carcinoma to develop in a woman 
Definition
Upper Outer Quadrant
Term
Of the following types of colonic polyps, the type that is most likely to become malignant is
Definition
Adenomatous
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