Pathology E3 Flashcards
tissue edema
intercellular fluid
anasarca
severe generalized edema
pulmonary edema
intraalveolar fluid
pleural effusion
fluid accumulation in pleural space
ascites
fluid accumulation in peritoneal cavitiy
transudate
increased hydrostatic pressure
clear
sterile
few benign cells
specific gravity <1.012
low protein content =<1 g/dl
fluid glucose ~ serum glucose
pleural effusion
hydrothorax
exudate
malignancy/inflammation
turbid/bloody
inflammatory cells
+ bacteria/other malignant cells
specific gravity >1.02
protein content >1g/dl
fluid glucose < serum glucose
hyperemia
increased blood flow (perfusion)
congestion
decreased blood outflow
hyperemia and congestion both can be considered as a ….
local increase in blood volume
can be acute and chronic
acute pulmonary congestion
sudden/acute pulmonary capillary engorgement and dilatation
leakage of fluids –> alveolar edema and filling of alveolar spaces with edema fluid
May be seen in sudden cardiac/ventricular arrhythmia w/ LV insufficiency
chronic pulmonary congestion
chronic capillary engorgement –> slow leaking of edema fluid into alveolar spaces and alveolar microhemorrhages
hemosiderin-laden macrophages –> heart failure cells
may be seen w/ ongoing LV insufficiency
hemosiderin-laden macrophages
heart failure cells
Petechiae
small punctate bleedings from capillaries
thrombocytopenia
Purpura
small bleedings slightly larger than petechiae, associated w/ blood extravasation from small arterioles
vasculitis
Ecchymoses
lg cutaneous bleedings
trauma
suspect abuse
hematoma
collection of blood in soft tissue or body cavities
shock
disordered microcirculation leading to
tissue hypoperfusion and ischemia
referring to end of capillary and venous
hypOperfusion
decreased flow of oxygenated blood due to obstruction of artery
ischemia
blood flow insufficient for metabolic requirements
infarct
ischemic necrosis
most common causes of hypOperfusion and ischemia
atherosclerosis
thrombosis/embolism
dec of arterial blood flow resulting from narrowing (stenosis/thrombosis) of arteries, can be acute and chronic
syndromes of acute ischemia
myocardial - angina pectoris
cerebral - TIA
leg muscles - claudicatio intermittens
Myocardial ischemia
(Angina Pectoris)
ischemic pain of heart muscle
coronary blood flow does not meet myocardial oxygen demand
most freq cause –> coronary artery stenosis
cerebral ischemia
transient ischemic attack (TIA)
most freq cause –> dec arterial blood supply due to arterial occlusion
presentation=short temporary dysfunction of brain (neurologic deficit)
ischemia of leg muscles
claudicatio intermittens
peripheral vascular disease (PVD)
dec. blood flow to lower extremity
chronic ischemia
organ atrophy
reduction in organ size due to apoptotic cell loss
fx influencing outcome of ischemia
Duration of hypoxia or anoxia Tissue tolerance Capacity of cells to regenerate Systemic Factors Type of arterial supply Collateral circulation
infarct
ischemic necrosis of tissue
caused by occlusion of arterial supply or venous drainage
most frequently via thrombosis or thromboembolic event
progression of tissue during MI
early MI (6-12 hr) - loss of cross striations, nuclei not present. Extensive hemorrhage at border of infarction (accounts for hyperemic border)
(12-2 hr)
(3 days): neutrophilic infiltrates w/ prominent necrosis and hemorrhage. extensive acute inflammatory cell infiltrates. myocardial fibers so necrotic that outlines are barely visible
1-2 weeks: granulation tissue. healing of infarct becomes more prominent, w/ capillaries, fibroblasts, macrophages (filled w/ hemosiderin)
More weeks: scar tissue
Hemostasis
response to vascular injury resulting in formation of a hemostatic plug
a well balanced well-regulated process.
- maintains blood fluidity in normal vessels
- provides hemostatic plug thrombus at the site of vascular injury. Clot is designed to seal the mural defect as a part of hemostasis.
response to vascular injury phases
- Arteriolar vasoconstriction
- Activation of platelets (primary hemostasis)
- Activation of coagulation cascade (secondary hemostasis)
- Activation of fibrinolytic system
endothelium functions
innermost cellular lining of blood vessels
Regulation of blood pressure Regulation of immune factors Regulation of inflammation Regulation of tissue fluid homeostasis Hormone synthesis Produces procoagulant and anticoagulant factors (regulation of blood clotting)
magacaryocytes
fragments of magacaryocytes –> platelets
platelet contents
ADP/ATP
epinephrine
serotonin
^ via dense bodies
fibrinogen von willebrand factor
^ via alpha granules
intrinsic coagulation cascade
activation by Factor XII present in the plasma
coagulation cascade
Set of enzymes that lead to formation of fibrin (insoluble) out of fibrinogen (soluble)
fibrinogen cleavage by THROMBIN –> insoluble molecules form (fibrin –> end of coagulation cascade)
extrinsic coagulation cascade
activation by Tissue Factor (TF)
thrombosis
pathologic activation of clotting mechanism w/ formation of thrombus (clot)
in uninjured vasculature (could be venous or arterial)
results in vascular occlusion after minor injury
thrombus –> NOT a hemostatic plug
small can be resolved via fibrinolytic mechanisms
hemostasis
Activation of platelets + humoral coagulation system (clotting factors)
Virchow’s triad
endothelial injury
abnormal blood flow
hypercoagulability
lead to thrombosis
risk fx for arterial thrombosis
coronary artery and MI
endothelial injury
exposes ECM –> activation of platelets and coagulation cascade
physical disruption not req. Endothelial dysfunction can be via DM, smoking, hypercholesterolemia
turbulence
at vascular bifurcation sites or areas of arteriosclerotic plaques
stasis
slowing of blood
hyperviscosity
increased cellular elements of blood
hypercoagulability
(thrombophilia)
disordered in coagulation pathways –> predisposed to thrombosis
caused by abnormal factor of coagulation cascade
Inherited and acquired thrombophilia
suspect if ... over 60 y/o (or earlier) or FHx spontaneous and/or massive DVT/VTE cerebral/visceral vein thrombosis VTE provoked by pregnancy/OCP/HRT
can be primary (hereditary) or secondary (acquired)
less important than endothelial injury/stasis
rare
Risk fx of hereditary thrombophilia
Mutation in Factor V = Factor V Leiden Prothrombia G20210A Gene Mutation Antithrombin III Deficiency Protein C Deficiency Protein S Deficiency Hyperhomocystinemia
Protein C
Protein S
deficiencies can lead to…
natural anticoagulant system
degrade factor V, factor VIII
undegradable coagulation factor
Acquired Risk Factors for Thrombosis
immobilization major surgery, fracture, burns Malignancy Myocardial Infarct Heparin Antiphospholipid antibody syndrome Pregnancy, contraceptives/estrogen Smoking
Fate of thrombi (3)
Thrombolysis
- If thrombus lyses in 1-5 days, clots removed by fibrinolytic system
Organization
- If thrombus has not lysed in 1-5 days
- Remodeling and recanalization of thrombus
Embolization
- Detachment and travel within circulation
(Embolus: detached intravascular mass carried by the blood to distant sites)
embolization
embolus trey transported until lodges in blood vessel
emboli can originate from venous or arterial circulation
pulmonary embolsm
Venous thrombi –. emboli that lodge in the pulmonary arterial tree
Over 80% of patients with PE have proven DVT
Most PEs originate from the lower limbs
Over 50% patients with DVT have silent PEs
DVT is a serious cause of morbidity and mortality
paradoxical embolism
emboli that cross from venous–> arterial circulation via septal heart defects
patent foramen ovale: hole in the wall between the heart’s upper chambers
arterial thromboembolism
Emboli originating within arterial circulation
Arise from chambers of the heart or heart valves 80% of the time
Other Examples of Emboli
Amniotic fluid emboli
Septic emboli (cardiac valve vegetations)
Air emboli
Fat emboli (trauma; motor vehicle accidents)
gangrene
infarct frequently affects structures like digits, extremities or sacral skin (nose)
dry coagulative necrosis –> dry gangrene
bacteria colonizing lesion –> wet gangrene
involves gas prod bacteria –> gas gangrene
infarct resolution process
necrosis - inflammation - repair
- 6-12 hr post injury –> nuclear and cytoplasmic changes of necrosis become visible
- 12-24 hr –> acute inflammatory rxn (neutrophil influx) develops pat infarct margin in the viable connective tissue
- By 1 week, macrophages and new capillaries invade the infarct from margins establishing granulation tissue, begins to lay down collagen
- 2-3 mo. infarct is converted to loose scar tissue which gradually matures to dense/contracted
Major risk fx of atherosclerosis
Age Sex (females more protected) Family history Genetic abnormalities Hyperlipidemia Hypertension Smoking Diabetes C-reactive protein
Minor risk fx of atherosclerosis
Obesity Physical inactivity Stress
Homocysteine (plasma >100 umol/L) Postmenopause Alcohol Lipoprotein (a) (alt form of LDL)
Unsat. Fat intake
non-modifiable risk fx of atherosclerosis
age
sex (men>women)
genetic
Modifiable risk fx for atherosclerosis
- HLD (high LDL, low HDL)
genetic defects in lipoprotein metabolism/genetic or acquired disorders like diabetes or hypothyroidism - HTN
- smoking
- DM
- C-reactive protein
A 44-year-old woman has a family history of heart disease. Her father and mother both developed congestive heart failure and myocardial infarction as a result of extensive coronary atherosclerosis. A dietary modification to include consumption of which of the following is most likely to reduce her risk for ischemic heart disease?
A. 40% of total caloric intake as fat
B. A diet high in saturated fat
C. 10% of total caloric intake as saturated fats
D. Fat found in beef products
E. Trans-fats
C.
An increased incidence of atherosclerosis has been correlated with all of the following except:
A. hypertension
B. diabetes mellitus
C. increased serum high-density lipoprotein (HDL) concentration
D. hyperuricemia
E. Use of oral contraceptives
C.
Principal point of physiologic resistance to blood flow
Arterioles
describe longitudinal section through the normal aorta with an elastic tissue stain
intima is at the top, while the thick aortic media demonstrates parallel dark elastic fibers
smc fibers are between the elastic fibers
vascular wall components
Endothelial cells Smooth muscle cells Extracellular matrix: -Elastic elements -Collagen -Proteoglycans
Weibel-palade bodies
3 mm long membrane-bound bodies that represent the storage organelle for von Willebrand factor
Endothelial Cell Properties and Functions
Maintenance of permeability*
Regulation of thrombosis,
thrombolysis and platelet adherence*
^most important
Extracellular matrix production (collagen, proteoglycans)
Modulation of blood flow and vascular reactivity
Regulation of inflammation and immunity
Regulation of cell growth
Metabolism of hormones
ECM is part of clot
smc functions
Vasoconstriction and dilation
Synthesis of collagen, elastin and proteoglycans (for matrix)
Elaboration of growth factors and cytokines
Migration to the intima and proliferation
Smooth muscles form which layer of arterial wall?
A- INTIMA
B- MEDIA
C- ADVENTITIA
endothelial cells form which part of arterial wall?
intima
Arteriosclerosis = hardening of the arteries
Used to describe 3 distinct patterns:
- Atherosclerosis
- Mönckeberg medial calcific stenosis
- Arteriolosclerosis
Mönckeberg medial calcific stenosis
in medium-sized muscular arteries (>50 years old)
(media)
calcifications in the media; note that the lumen is unaffected by this process
when calcified muscular arteries show up on a radiograph of the pelvic region in an older person
most clinically INsignificant
Atherosclerosis (where are plaques comm. found?)
formation of intimal lipid rich fibrous plaques
Plaques commonly found at bifurcation points of arteries
(Turbulent flow/eddy currents vs. smooth,
laminar flow
Shear stress at high flow rates)
Arteriolosclerosis (which diseases associated w/?)
disease of SMALL arteries and arterioles, association with hypertension and diabetes mellitus
Atherosclerosis affects largely
elastic and muscular arteries
Hypertension and Diabetes affect primarily
small arteries and arterioles
hyperplastic arteriolosclerosis
Leakage of plasma proteins, excessive extracellular matrix production. Arteriolar wall is markedly thickened.
Narrowed lumen impairs glomerular blood supply.
ONION-SKIN appearance
more comm. in benign HTN, DM, elderly
Hyaline Arteriolosclerosis
Lamellar re-duplication of intimal smooth muscle cells. ECM goes out of lumen and deposits in wall
Severe benign hypertension, accelerated hypertension
May be accompanied by fibrinoid necrosis
more comm. in diabetic kidneys
(does not have layer of cells like hyper plastic, instead just has thick pink material)
MALIGNANT HYPERTENSION
Extremely high blood pressure (typically >180/120) that develops rapidly, causes organ damage + papilledema.
Tx: medical emergency
Causes: h/o Hypertension, missing dose of medication Collagen vascular disease Renal disease Tumors of adrenal glands Cocaine
Complications: Aortic dissection Coma Pulmonary edema Heart failure Renal failure
Which type of vessels are most affected by atherosclerotic changes?
- Elastic arteries
- Small arteries
- Capillaries
- Muscular arteries
A. 2 and 3
B. 4 and 1
C. 1 and 2
D. 1 and 3
B.
Precursors of Atheromatous Plaque
- Fatty streaks
- Intimal thickening (intimal cell mass)
- white, at branch points
- contain smc and CT but NOT lipid (trying to heal trauma)
Fatty streaks
Appear in aorta of children younger than 1 year of age and all children older than 10 years
Flat
Multiple yellow, flat spots (<1 mm), later elongated streaks
Precursors of atheromatous plaques
Composed of lipid filled foam cells with T lymphocytes and extracellular lipid (low density and very low density lipoproteins)
Foamy macrophages
macrophages w/ fat
precursors of Atheromatous Plaque
Progression of Atherosclerotic Lesions
Isolated Macrophage –> Fatty Streaks
Intimal Thickening –> Extracellular Lipids –> Atheroma –> Fibroatheroma –> complex lesion
Precursor lesion for atheroma is –
A Thrombus B Fatty streak C Calcification D Hemorrhage E Exudate F Ulceration
B
Atheromatous Plaque
Characteristic lesion of atherosclerosis
Raised focal plaque within the intima with a lipid core and a covering fibrous cap
Form 0.3-1.5 cm, sometimes larger masses
More common in abdominal aorta and its major branches
Atheromatous Plaque 3 principal components
Cells: Smooth muscle cells, macrophages, leukocytes
CT, ECM – collagen, elastic fibers, proteoglycans
Intracellular and extracellular lipid deposits
CHL clefts indicate
an acute injury not a chronic injury
SEQUELAE OF ATHEROSCLEROSIS
- Nothing happens
- Slowly decreasing blood supply
- Fibrous cap breaks causing thrombo embolism
- Hemorrhage from vaso vasorum in adventitia causing lumen occlusion
- Ulceration of surface
- Calcification
- Aneurysm/arterial rupture (balloon shaped protrusion of vessel wall)
clinical phases of atherosclerosis
aneurysm and rupture
occlusion by thormbus
critical stenosis
anterior descending coronary artery w/ marked atherosclerosis with narrowing. In general, the worst atherosclerosis is _____, where arterial blood flow is _______________.
worst atherosclerosis is proximal, where arterial blood flow is more turbulent
Which arterial layer is involved in atherosclerosis?
intima and media
What type of arteriosclerosis is least significant clinically?
Mönckeberg medial calcific stenosis
What is the early pathological lesion of atherosclerosis?
intimal thickening
What are the two risk factors for arteriolosclerosis?
HTN, DM
Where is arteriolosclerosis usually found?
kidneys
What is the most common cause of aneurysms?
atherosclerosis
Where do atherosclerotic aneurysms occur?
abd aorta
vasculitis
Inflammation of and damage of vessel wall, typically arteries are involved
vasculitis etiologies
Autoimmune processes ( immune complex deposition, ANCA, or antibodies against endothelial cell antigens ) Infection
Giant cell temporal arteritis sx causes location tx
large cell
Arteries, esp. cranial
Cause unknown. Poss immunologic basis, responds to steroids
Pain and tenderness over temporal area of head and may include jaw pain
Involvement of branches of the ophthalmic artery may lead to sudden loss of vision
Usually >50-60 yrs old
Associated with polymyalgia rheumatica; elev. ESR (60)
Giant cells and lymphocytes; intimal fibrosis
TX: 60mg prednisone
Polyarteritis nodosa
medium vessel
Necrotiz inflamm of renal arteries
30% of those with PAN have Hep B antigen in serum
Immune cells mistake antigens on blood vessel for hep B
Systemic (multi-organ) and segmental involvement of small and medium arteries
Usually young adults, most commonly males
Thromboangiitis obliterans (Buerger’s Disease)
Intermediate and small arteries, sometimes veins typically of the extremities (hands and feet)
Usually young adults, before age 35
Strong association with heavy cigarette SMOKING
Occlusive thromboses with microabscesses
Abdominal Aortic Aneurysm (AAA)
Intrinsic or acquired defect in wall
Most comm assoc with atherosclerosis
Typically involves aorta below renal arteries and above iliac bifurcation
Other forms:
Vasculitis
Trauma
Infections (mycotic)
Risk of AAA rupture is directly related to the size…
- Nil for 4cm AAA
- 1% per year for 4-5cm AAA
- 11% per year for 5-6cm
- 25%per year for 6cm and larger
AAA RUPTURE TRIAD
- Abrupt onset of severe back pain
- Hypotension
- Pulsative mass
Berry Aneurysms
Bifurcations of circle of Willis
0.5 - >3 cm
May be multiple
Etiology…
Genetic factors
Cigarettes
Hypertension
Syphilitic Aneurysm
cardiovascular manifestation of tertiary syphilis
Typically affects ascending aorta and arch in males 40-55 y/o
Obliterative endarteritis of vasa vasorum leads to ischemic fibrosis of aortic media
Vasculitis with prominent plasma cell infiltrate
Compression/erosion of airways, esophagus, bone; rupture
Aortic Dissection
Entry of blood into wall of the aorta through a tear in the tunica intima and the subsequent pushing apart of the wall layers (tunica media)
Occurs in weakened aortic wall
presenting sx: abrupt onset of severe chest pain and/or back pain between the shoulder blades, pair described as “tearing pain”
Aortic Dissection Risk Factors
- Older age
- CHRONIC Hypertension
- Connective tissue disorders
- Association with Marfan syndrome(defect in fibrillin), Ehler-Danlos syndrome(defect in collagen), coarctation, bicuspid aortic valve - Cystic medial degeneration- most frequent pre-existing histologically detected lesion
Most frequent pre-existing abnormality in aortic dissection
Cystic Medial Degeneration
Cystic Medial Degeneration
Separation and loss of elastic elements in aortic media; cyst-like spaces filled with mucopolysaccharide rich matrix
Sequelae of aortic dissection
Rupture into surrounding soft tissues Rupture into pericardial space (hemopericardium) Rupture into pleural space (hemothorax) Re-entry into aortic lumen Compression of branch ostia
