5. WATER • 60% of body
• 2/3 of body water is INTRA-cellular
• The rest is INTERSTITIAL
• Only 5% is INTRA-vascular
• EDEMA is SHIFT to the INTERSTITIAL
SPACE
• HYDRO-
– -THORAX, -PERICARDIUM, -PERICARDIUM
• EFFUSIONS, ASCITES, ANASARCA
18. Transudate vs Exudate
• Transudate
– results from disturbance of Starling forces
– specific gravity < 1.012
– protein content < 3 g/dl
• Exudate
– results from damage to the capillary wall
– specific gravity > 1.012
– protein content > 3 g/dl
50. NORMAL platelet on LEFT, “DEGRANULATING” ALPHA
GRANULE ON RIGHT AT OPEN WHITE ARROW
51.
52. PLATELET PHASES
• ADHESION
• SECRETION (i.e.,
“release” or “activation”
or “degranulation”)
• AGGREGATION
53. PLATELET ADHESION
• Primarily to the
subendothelial ECM
• Regulated by vWF, which
bridges platelet surface
receptors to ECM collagen
54. PLATELET SECRETION
• BOTH granules, α and δ
• Binding of agonists to
platelet surface receptors
AND intracellular protein
PHOSPHORYLATION
55. PLATELET AGGREGATION
• ADP
• TxA2 (Thromboxane A2)
• THROMBIN from coagulation
cascade also
• FIBRIN further strengthens
and hardens and contracts the
platelet plug
56. PLATELET EVENTS
• ADHERENCE to ECM
• SECRETION of ADP and TxA2
• EXPOSE phospholipid
complexes
• Express TISSUE FACTOR
• PRIMARYSECONDARY PLUG
• STRENGTHENED by FIBRIN
62. ENDOTHELIAL “INJURY”
• Jekyll/Hyde disruption
–any perturbation in the dynamic
balance of the pro- and
antithrombotic effects of
endothelium, not only physical
“damage”
65. ABNORMAL FLOW
•NON-LAMINAR FLOW
• TURBULENCE
• EDDIES
• STASIS
• “DISRUPTED” ENDOTHELIUM
ALL of these factors may bring
platelets into contact with
endothelium and/or ECF
66. 1˚ HYPERCOAGULABILITY
(INHERITED)
• COMMONEST: Factor V and
Prothrombin defects
• Common: Mutation in prothrombin gene,
Mutation in methyltetrahydrofolate gene
• Rare: Antithrombin III deficiency, Protein C
deficiency, Protein S deficiency
• Very rare: Fibrinolysis defects
74. D.V.T. • D. (CALF, THIGH, PELVIC) V.T.
• CHF a huge factor
• INACTIVITY!!!
• Trauma
• Surgery
• Burns
• Injury to vessels,
• Procoagulant substances from tissues
• Reduced t-PA activity
75. ARTERIAL/CARDIAC THROMBI
• ACUTE MYOCARDIAL INFARCTION =
OLD ATHEROSCLEROSIS + FRESH
THROMBOSIS
• ARTERIAL THROMBI also may send
fragments DOWNSTREAM, but these
fragments may contain flecks of
PLAQUE also
• LODGING is PROPORTIONAL to the %
of cardiac output the organ receives,
i.e., brain, kidneys, spleen, legs, or the
diameter of the downstream vessel
77. Disseminated Intravascular Coagulation
D.I.C.
• OBSTETRIC COMPLICATIONS
• ADVANCED MALIGNANCY
NOT a primary disease
CONSUMPTIVE coagulopathy, e.g.,
reduced platelets, fibrinogen, F-VIII and
other consumable clotting factors,
brain, heart, lungs, kidneys,
MICROSCOPIC ONLY
78.
79. EMBOLISM
•Pulmonary
• Systemic (Mural Thrombi and
Aneurysms)
• Fat
• Air
• Amniotic Fluid
80. PULMONARY EMBOLISM
• USUALLY SILENT
• CHEST PAIN, LOW PO2, S.O.B.
• Sudden OCCLUSION of >60% of
pulmonary vasculature, presents a HIGH
risk for sudden death, i.e., acute cor
pulmonale, ACUTE right heart failure
• “SADDLE” embolism often/usually fatal
• PRE vs. POST mortem blood clot:
– PRE: Friable, adherent, lines of ZAHN
– POST: Current jelly or chicken fat
81.
82.
83. SYSTEMIC EMBOLI
• “PARADOXICAL” EMBOLI
• 80% cardiac/20% aortic
• Embolization lodging site is
proportional to the degree of flow
(cardiac output) that area or organ
gets, i.e., brain, kidneys, legs
84. OTHER EMBOLI
•FAT (long bone fx’s )
•AIR (SCUBA bends)
•AMNIOTIC FLUID,
very prolonged or difficult
delivery, high mortality
85.
86.
87. INFARCTION
• Defined as an area of necrosis*
secondary to decreased blood
flow
• HEMORRHAGIC vs. ANEMIC
• RED vs. WHITE
–END ARTERIES vs. NO END ARTERIES
• ACUTEORGANIZATIONFIBROSIS
88. INFARCTION FACTORS
• NATURE of VASCULAR SUPPLY
• RATE of DEVELOPMENT
–SLOW (BETTER)
–FAST (WORSE)
• VULNERABILITY to HYPOXIA
–MYOCYTE vs. FIBROBLAST
• CHF vs. NO CHF
98. SEPTIC shock
• OVERWHELMING INFECTION
• “ENDOTOXINS”, i.e., LPS (Usually Gm-)
• Gm+
• FUNGAL
• “SUPERANTIGENS”, (Superantigens are polyclonal
T-lymphocyte activators that induce systemic inflammatory
cytokine cascades similar to those occurring downstream
in septic shock, “toxic shock” antigents by staph are the
prime example.)
99. SEPTIC shock events*
(overwhelming infection)
• Peripheral vasodilation
• Pooling
• Endothelial Activation
• DIC
* Think of this as a TOTAL BODY
inflammatory response
100. ENDOTOXINS
• Usually Gm-
• Degraded bacterial cell wall products
• Also called “LPS”, because they are Lipo-
Poly-Saccharides
• Attach to a cell surface antigen known as
CD-14
Areas of increased vascular permeability or areas of increased blood vessels will appear “edematous”
Arterial pressure, venous pressure, colloid oncotic pressure, and competent lymphatic vessels are the main factors of edema
CHRONIC congestion usually implies necrotic or damaged tissued due to chronic lack of adequate perfusion. CONGESTION is more associated with edema than HYPEREMIA is because DECREASED VENOUS FLOW, rather than INCREASED ARTERIAL FLOW, is the prime feature which differentiates CONGESTION from HYPEREMIA.
CONGESTION, as a common CLINICAL term, is often used interchangeably with the term EDEMA or HYPEREMIA
ACUTE passive CONGESTION (HYPEREMIA) of the lung, PRECEDES ACUTE PULMONARY EDEMA
Pulmonary edema occurs only when the pulmonary capillary pressure rises to values exceeding the plasma colloid osmotic pressure, which is approximately 28 mm Hg in the human. Because the normal pulmonary capillary pressure is 8 to 12 mm Hg, there is a substantial margin of safety in the development of pulmonary edema.
At pressures of 12 to 18 mm Hg, the vessel borders become progressively hazier because of increasing extravasation of fluid into the interstitium. This effect is sometimes evident as Kerley B lines, which are horizontal, pleural-based, peripheral linear densities. As PCWP increases above 18 to 20 mm Hg, pulmonary edema occurs, with interstitial fluid present in sufficient amounts to cause a perihilar &quot;bat wing&quot; appearance.
Air bronchogram and Kerley B findings
Heart failure cells are hemosiderin laden macrophages. Blood escapes into the alveolar space because chronic congestion causes the thin walled alveolar capillaries to burst..
Note the thickening of the alveolar septae. This is caused by chronic pulmonary congestion and edema.
CHRONIC passive CONGESTION (HYPEREMIA) of the lung, is characterized by hemosiderin laden macrophages due to breakdown of RBCs
CHRONIC passive CONGESTION (HYPEREMIA) of the liver, is classically also termed “NUTMEG” liver, and is associated with necrosis in the CENTRAL part of the hepatic lobule. This can progress to cirrohisis, and therefore if the congestion is cardiac in origin, the type of cirrhosis is called CARDIAC cirrhosis
Flattened gyri often signify edema. Why? Ans: compression against the calvarium
1) Falx, 2) Cingulate, and 3) Cereballar tonsillar levels of edema
This parallels the changes in color of bruises and the difference in chemistry makes possible differences in MRI appearances and enables TIMING to be estimated
EPI-dural, SUB-dural hematomas
Splenic, renal? hematoma
CT can only show the DENSITY of the hematoma, MRI can show its chemistry and evolution, and therefore help ESTIMATE the time of hemorrhage
The differentiation between hemorrhage and thrombus is often a moot point in clinical medicine. The differentiation between a post-mortem from a pre-mortem clot is often crucial diagnostically.
A new Hollywood epic
Endothelial cells have a Dr. Jekyll and Mr. Hyde personality
Endothelial cells have a Dr. Jekyll and Mr. Hyde personality
Endothelial cells have a Dr. Jekyll and Mr. Hyde personality
Megakaryocyte “pinching” off platelets
Guess which ones are the DENSE granules?
NOTE particularly at the three processes of inhibition in red: TFPI (Tissue factor pathway inhibitor), Antithrombin (III), Protein C
Endothelial cells have a Dr. Jekyll and Mr. Hyde personality
Endothelial cells have a Dr. Jekyll and Mr. Hyde personality
Hypercoagulability is anything which accelerates the cascade, or inhibits its inhibitors
Most (80%) of systemic arterial thrombi come mural thrombi, most of the rest (20%) come from the aorta
DEEP PELVIC VEIN THROMBUS, the prime source of pulmonary emboli, the other source would be deep pelvic veins. SUPERFICIAL veins do NOT usually embolize to the lungs.
Because DVT is the major source of PE, the risk factors for BOTH are identical.
Lines of Zahn, gross and microscopic, top, is evidence to prove a clot is PRE-mortem.
Clots appearing like current jelly or chicken fat are said to be POST-mortem.
In general, post mortem clots are rather AMORPHOUS and have no binding texture when you squeeze them
FAT (marrow) embolism in a pulmonary artery
FAT (marrow) embolism in a pulmonary artery
RED (HEMORRHAGIC) PULMONARY INFARCT, and ANEMIC (WHITE) SPLENIC INFARCT
WEDGE SHAPED SCARRED INFARCT following the distribution of a end artery branch of the renal artery. FIBROSIS implies that it is old (months to years)
DAD is also called “shock” lung
Myocardial Necrosis. Note the lower field contains intact myocardium, while the upper field exhibits coagulation necrosis of myocardium. In shock the hypoperfusion is greatest in the subendeocardium, which is perfused mainly in diastole.