anatomic path exam 2

Structure of artery vs vein

• artery → thick wall w/ high elastin to absorb high pressure from blood leaving the heart

  • tunica intima

    • endothelium

    • internal elastic lamina

  • tunica media

    • smooth m.

    • external elastic lamina

    • elastic fibers

  • tunica adventitia

    • vasa vasorum

    • lymph

    • nn.

    • CT

• vein → large lumen + little muscle + few elastin allows more blood to pool and prevent backflow

  • tunica intima

    • just endothelium

  • tunica media

    • smooth m.

  • tunica adventitia

    • vasa vasorum

    • some CT

3 types, fxns, and examples of the diff. endothelium in capillaries

• continuous endothelium = tight jxns allow strict control of transfer of water, gases, ions

  • ex) blood brain barrier, mm, lung, bone

• fenestrated endothelium = pores allow transfer of small molecules, lim. protein

  • ex) renal glomeruli, intestinal villi, endocrine glands

• discontinuous/sinusoidal endothelium = large gaps allow free transfer of proteins, blood cells

  • ex) liver, spleen, bone marrow, lymph nodes

What is endothelial activation?

• localized response of endothelial cells

• endothelial cells undergo changes to enter a proinflammatory state

What are the 5 categories of mediators produced by endothelium w/ examples?

• vasodilation/vasoconstriction

  • vasodilation ex: NO

  • vasoconstriction ex: endothelin

• hemostasis (antihemostatic + prohemostatic)

• inflammatory mediators

  • cytokines

  • cell adhesion molecules

• growth factors

  • for smooth muscle + fibroblasts

  • colony stimulating factors

• fibrinolysis

  • fibrinolytic components

Basic structure + mechanism of lymphatic vessel

• overlapping endothelial cells

• large interendothelial gaps

• external pressure moves fluid into lymph vessel

• intravascular pressure hold overlapping edges to prevent fluid escaping vessel

What does in = out regarding the microcirculation?

• amt of fluid leaving arteriole end of capillary = amt of fluid entering venule end + lymphatic vessel

What is the interstitium made of and what is its general fxn?

• general fxn: structural framework for cells + supp microvasculature

  • allow diffusion of gases to/from cells up to 1mm away from capillary

• includes ECM

  • collagen

  • adhesive glycoproteins

  • absorptive glycosaminoglycans + proteoglycans

Is most of the water in the body intracellular or extracellular?

• 2/3 intracellular

• 1/3 extracellular

2 ways stuff moves across plasma membranes? What stuff falls under each category?

• free mvmt

  • nonpolar = lipid soluble substances

  • gases, water

• carrier-mediated

  • polar = lipid insoluble substances

  • ions, glucose, AAs

What is edema? What are the 4 basic mechanisms of edema w/ examples?

• edema = accumulation of fluid (transudate) in extravascular space

  • transudate = water, clear, low in protein + cells

  • never primary process, edema is always secondary process

1) decreased plasma oncotic pressure

• ex) hypoproteinemia

2) increased capillary hydrostatic pressure

• ex) venous obstruction, heart failure causing more fluid back up in circulatory system causing inc. capillary hydrostatic pressure

3) lymphatic obstruction

• ex) lymphatic obstruction/compression

4) increased vascular permeability aka inflammatory edema

• ex) inflammatory agents

How to recognize edema grossly + microscopic?

• grossly

  • swollen

  • pits on pressure

  • spongy

  • pale

  • cool to touch

  • ± pain

• microscopic

  • expansion of INTERcellular spaces

  • pale eosinophilic fluid

What is dehydration? What are the consequences? How do you recognize?

• dehydration = inadequate amt of body water (incl. extracellular + intracellular fluid)

• consequences:

  • decreased CO

  • decreased blood volume

  • decreased tissue perfusion

  • decreased renal fxn

  • 10-12% dehydration can be fatal

• CBC/chem signs:

  • increased PCV = increased solids in blood

  • hyperproteinemia = increased albumin

• clinical signs:

  • skin tenting

  • tacky gums

  • sunken eyes

  • increased CRT

Pathogenesis of edema in glomeular amyloidosis?

• chronic inflammatory state → inc. SAA → persistent SAA elevation → conversion to amyloid A → deposition of amyloid A fibrils in glomeruli → impaired glomerular filtration → protein loss thru kidney → hypoproteinemia → decreased vascular oncotic pressure → fluid builds up in interstitium + abdomen → edema + ascites (edema in abdominal cavity) + hydropericardium + hydrothorax

What is hemostasis? Describe the general normal hemostatic process

• hemostasis = arrest of bleeding

  • balance b/t coagulation/clotting + fibrinolysis

1) primary hemostasis = transient vasoconstriction + formation of primary platelet plug

• if very minimal vascular injury → proceed to step 4) healing/tissue repair

2) secondary hemostasis = generation of fibrin clot

3) fibrinolysis = breakdown of fibrin clot

4) healing/tissue repair

Role of endothelium, platelets, and coagulation cascade in normal hemostasis

• endothelium

  • healthy → prod. anticoagulant factors

  • damaged → prod. procoagulant factors

• platelets = phospholipid membranes that have anucleate cytoplasmic frags of megakaryocytes (precursor cell) + cytoplasmic granules + surface receptors

  • Gp1b surface receptor → binds von Willebrand Factor → adherence of platelet to endothelial wall

  • Gp2b-3a surface receptor → binds fibrinogen

    • fibrinogen = initial bridge b/t platelets (precursor to fibrin which is the actual glue) → necessary for platelet aggregation

• coagulation cascade = series of enzyme reactions that results in fibrin

  • tissue injury (extrinsic pathway) → endothelial cells release tissue factor (TF) → more enzyme rxns → activated thrombin turns fibrinogen into fibrin

    • fibrin = mortar/glue for platelet bricks

Major events of primary hemostasis

• primary hemostasis = transient vasoconstriction + platelet plug formation

• transient vasoconstriction:

  • vascular injury → endothelium releases endothelin-1 (vasoconstrictor mediator) → transient vasoconstriction

    • slows things down to buy time for bricks (platelets) to build-up

• platelet plug formation:

  • platelets adhere directly to subendothelial matrix

  • endothelial cells release vWF → platelets bind vWF via their Gp1b surface receptor → stronger glue

  • platelet activation + granule release → trigger fibrinogen binding

    • thromboxane A2 → platelet aggregation, vasoconstriction

    • ADP → triggers fibrinogen binding

Major events of secondary hemostasis + coagulation factors involved in fibrin formation

• secondary hemostasis = if primary hemostasis insufficient → generation of polymerized fibrin clot

  • endothelial cells release tissue factor (TF) → initiates extrinsic coagulation cascade

  • thrombin → converts fibrinogen to fibrin

    • fibrin polymerizes → cements platelets into secondary hemostatic plug

What is the result of the coagulation cascade?

thrombin converts fibrinogen → fibrin

Major events of fibrinolysis + clinical relevance of its end products?

• fibrinolysis = breakdown of fibrin clot

  • anticoagulant + fibrinolytic factors released → lim. hemostatic process + facilitate thrombus dissolution

  • antithrombin → inactivates thrombin → stops fibrinogen from being converted into fibrin

  • tissue plasminogen activator (tPA) → converts plasminogen into plasmin

  • plasmin → blows up clot → fibrin degradation → prod. fibrin degradation products (FDPs)

  • D-dimers = important FDP that can be measured to determine if fibrinolysis is happening → testing for DIC, septicemia, PTE

What do elevated D-dimer levels indicate?

breakdown of cross-linked fibrin is occurring

Endothelin definition/fxn

• primary hemostasis

• vascular injury → endothelium releases endothelin-1 = vasoconstrictor mediator → transient vasoconstriction

  • slows things down to buy time for bricks (platelets) to build-up

TF definition/fxn

• tissue injury → endothelial cells release tissue factor (TF) → activates coagulation cascade enzyme rxns via extrinsic pathway → activated thrombin turns fibrinogen into fibrin

3 important endogenous anticoagulants/coagulation inhibitors + how they work?

• antithrombin (AT)

  • main anticoagulant

  • inhib. most coagulation factors

• tissue factor pathway inhibitor (TFPI)

  • stored in platelets → released at injury sites

  • prevents start of excessive thrombin generation

• protein C

  • thrombin + thrombomodulin activates protein C → inhib. some coagulation factors

  • occurs on healthy, undamaged endothelium

  • prevents excessive clotting spread→ keeps clotting where we want it

vWF definition/fxn

fibrin definition/fxn

thrombin definition/fxn

plasminogen definition/fxn

tPA definition/fxn

FDP definition/fxn