describe hydrostatic pressure as a form of normal fluid exchange.

describe what occurrs at the arteriolar and venular ends. 

pressure of water influenced by the activity of the heart as a pump, and elasticity and recoil of blood vessels. 

ateriolar end of capiliary bed: OP < HP. therefore, fluid moves OUT of capilaries through pores, and the junctions between endothelial cells. 

- fluid that has moved termed ultrafiltrate (made of water, salts and small organic molecules)

venular end of capillary bed: OP> HP. therefore, fulid moves INTO capillaries (most ultrafiltrate retunred. any remaining fluid drains from tissue via lymphatic system which eventually drains into blood). 

what is edema?

what is pitting edema?

edema is the accumulation of excess fluid is the tissue spaces. 

pittig edema is when the skin is affected 

the clincial effect of an edema is effusion (tissue fluid accumulation in body caviites). list 4 areads in the body this can occur. 

does it affect function of organs?

1. pleural space (between surface of lung and lining of chest wall)
2. pericaridal space (membranous sac which surrounds heart
3. peritoneal cavity (abdominal cavity, limited by diaphragm, abdominal walls and pelvic floor. speicies name ascites. 
4. anasarca (whole body edema)

these all affect function of organs! 

name and describe the two imortant causes of locailzed edema 

what's the two other causes? 

venous obstruction

- when venous drainage obstructed, fluid will leave capillaries normally at arteriolar end (HP>OP). but can't return to capillaries as easily at venular end as HP is still >OP. 

- veins are thinner walled than arteries, so they're more easily effected by obstruction. (extend of edema depends on size of vessle, how completely its obstructed and extent of vollateral circulation. 

- cause of more immediate edema, but lymph can also cause edema over time (since responsible for remvoing only remaining fluid and proteins) 

lymphatic obstruction

- accumulation of small protein molecules over time will lead to increaesd tissue colloid (substance microscopically dispersed evenly throughout another substance) OP (normally zero), which favours fluid to remain behind because plasma OP is insuffiecnt to pull fluid back into capillaries which leads to edema. 

two other causes:

acute inflammation and actue allergic reactions due to increased capillary permeability. 

congestive heart failure is caused by which form of edema?

it is a pathophysiologic condition caused by anything which? give 3 examples. 

describe what occurs during right and left ventrical failure. 

formed from generalized edemia. 

caused by anything which decreaseds cardiac output. 

1. decreasing contractility of heart muscle

2. mecahinical abnormaility

3. electiral disturbance (arrhythmias)

right venrtiral failure -> venous blood "backs up" -> generalized increase in venous pressure -> as if there is body wide venosu obstruction -> systemic edema! (most noticable in lowe parts due to grav)

left ventircal failure -> blood builds up in pulmonary circulartion (pulmonary venous congestion) -> increased HP -> fluid leaves capillaries (normal fucntion is at low HP) -> moves into alveolar spaces -> pulmonary edema! (will interere with gas exhcnage in lungs) -> dyspnea (sensation of shortness of breath) varies from mild to severe. 

hypoproteimemia (abnoramly low protein in blood) symptoms.

is second major cause for which type of edema?

causes?

effectt? 

low levels of serum protein and decpresed plasma OP.

second major cause for generalized edemia

insufficient dietary protein intake, decreased synthesis of albumin in liver, increased loss of albumin into intestine or into urine (albumin is snythesized in liver and is major determinant of plasma OP). 

because of decreased plasma OP, there is overall decrease in plasma volume leading to decreased glomerular filtration 

what common result of both heart failure and hypoproteinemia determine the volume of the edema? 

outline process

sodium and water retention 

decreased cardiac out -> decreased glomerular filtartion pressure in kidney -> renin proudction by juxtaglomerular apparatus -> increased aldosterone proudction in adreneal cortex -> increased Na resportion and water retention by distal tubules. 

passive process resulting from impiared venous return to tissue. can occur systemically (cardiac failure) or locally (venus obstrution). 

Blue -red colour (cyanosis). closely related to development of edema. 

regarding chronic passive congestion of the liver, what occurs during:

long lasting congestion

gross changes

microscopic changes 

long lasting congestion -> chronic passive congestion -> poorly oxygenated blood -> chronic hypoxia -> parenchymal cell degeneration/death and capilary rupture -> hemorage -> RBCs debris -> hemosiderrin 

gorss changes: loss of cells -> central lobular regions grossly red-brown and slighly depressed, surrounded by unconjugated tan, somtimes fatty liver. 

microscopic changes: heptaocyte drop out, hemorrgage, macrophgaes, maybe heptic fibrosis. 

define hemorrhage 

caused by? 

presence of blood in interstial tissues due to injury to blood vessels 

ruputre of vessel wall due to:

- vascular injruy, such as truama

- atherosclerosis (artey wall thickens from accumulating fat)

- inflammatory or neoplastic erosino of vessel wall 

or  could be caused by:

- cut, surgery or sponteous hemorrage wihtout trauam (ie nose bleed) 

petechiae: small, pinpoint focal hemorrhages

purpura: 3-5mm, oval to irregularly shaped

ecchymoses (bruises): larger area

hematoma: large "blood blister" where blood pooled within a tissue 

volume of blood loss (> 20% leads to hypovolemic shock)

rate of blood loss

amount of iron lost

site of hemorrhage 

list, in detail, the geneal sequence of events for normal hemostasis [make bleeding stop] (4 main steps)

which three genreal componenet are this sequnce dependent upon?

1. transient arteriolar vasoconstriction

- attributable to neurgoencic mechanisms

- augemneted by local secretion of endothelin

- trasient effect only - need activation of platelets and coagulation 

- caused by contraction of smooth muscle in the vessel wall 

- effective for hemostasis in small vessels, but not for large ones. 

2. formation of hemostatic plug (1o hemostasis)

- platelets adhere to exposed extracellular matrix  via vonWillebrand factor -> shape change and activation -> release of secretory granules (ADP and Thromboxane, TXA) -> recruitment of more platelets (Aggregation) -> hemostiac plug

3. foramtion of fibrin clot (2o hemostasis)

- tissue factor (membrane-bound procoagulant factor synthesized by endothelium), in conjugation with platelet factors, activates coagulation cascade -> activation of thrombin -> conversion of fibrinogen to fibrin + additional platelet aggregation and granule release _> fibrin polymerization 

4. formation of permanetn plug

- polymerized fibrin and platelet aggregates

- release of tPA (tissue plasminogen activator) and thromboulin (intereres with coagulation casade) limits the hemostaitc process to the site of injury 

dependend on:

- vascular wall, platelets and coagulation cascade. 

antithrbomic properites

1. antiplatelt effects: endothelium must be intact to prevent platelets from meeting highly thrombenic subednotheial extracellular matrix. non-activated platelets will not adhere. If activated, then prevented from adhering by enothelial prostacyclin (PGI2) and NO(potent vasodilators and inhbitors of platlet aggreation; syntheisis stimulated by factors proudced during coagulation. 

2. antiocagulant properites: mediated by membrane-associated, herpin like molecules and thrombomodulin (has specfic hormone receptor, which converting thrombin to an anticoagulant enzyme from a procoagulantenzyme) 

3. fibrinolytic properites: tPA to clear fibrin deposits from enodthelial surfaces 

prothrombotic properties 

- synthesis of vonWillebrand factor (which platelets adhere to)

- enothelial cells are induced by cytokines or bacterial endotoxin to secrete tissue factor

- binding to activated coagulation factors to augment their activities 

- secretion of inhibitors of plasminogen activators (which degrad fibrin clots) 

what are platelets

what two protaglandins are their function modulated by?

smaller than RBCs, appear as membrane bound smooth disks, lacking nucleous. 

function modulated by:

- PGI2 (enothlium derived)- vasodilator, inhibits aggregation

- TXA2 (platelet-dervided)- vasoconstrictor, activates aggregation 

1. adesion and shape change: mediated by interaction with vWF, which acts as a bridge between platelet surface receptors and exposed collagen

2. secretion: released Ca important for coagulation cascade; ADP is potent mediator of platelet aggregation, and also augments ADP release from other platelets. 

- surface expression of phosphlipid complex provides critical nucleation and binding sites for Ca and coagulation facots in intrinsic clotting pathway 

- injured or activated enothelial cells release TF to activate extrinsic coagulation cascade 

3. aggregation: ADP and TXA2 important stimuli for aggregation (set up autactalytic reaction, leading to enlarging platelet aggregate: 1o plug). Concurrent activation of coagulation leads to generation of thrombin, which binds to platelet surface receptors and further aggregation, leading to 2o plug 

to form thrombin (which allows conversion of soluble fibrinogen into insoluble fibrin) 

produce fibrin: to allow clot formation 

intrinsic pathway:

- initiated in clincial lab by activation of F XII

extrsinsic pathway:

- Activated by TF, a cellular lipprotein present at site of injruy 

calcium ions

phospholipid surface

vitamin K for synthesis of prothrombin and clotting factors VII, IX and X. 

through natural anticoagulatnts (antithrombin and proteins C and S)

and fibiolysis 

- Proenzyme plasmoinogen is incorperated into developing clot. its later activated to plasmin through either factor XII (dependent pathway or via action of plasminogen activators)

- tPa(From enothlial cells) is a useful theruapetic agent to manage thrombosis

- plamsimn acts to break down fibrin and also interferess with polymerization. Fibrin breakdwon products are themselves weak anticoagulants. 

clincal mainifestation: tendency to bleed excesively following minor trauma

defiecny of coagulation factors

-  hemophilia A (factor VII)

- vWF disease (reeduced levels or vWF + deficeint factor VII complex) 

increased anticoagulation activity

- induce factor defiences (ingestion of vit K antagonsists by cattle -> sweet clover poisoning) 

clincial manifesations: "small bleeds" in skin, particulary petechiae and purpura

thrombocytopenia (decreased platelet numbers) due to:

- deficent proudction or maturation in bone marrow

- abnormal distrubtion within body

- increased destruction

abnormailites of platelet function

- varitey of congential diseases

- can be induced by asprin 

clotting: protective

thrombosis: no benefiical effect; clotting within a vessel 

area of atttachment to the underlying vessel/heart wall, frequently firemest at the point of origin.

lines of zaha: laminations produced by pale layers of platelets and fibrin that laternate with darker layers containing more RBCs. 

differeniate between arterial thrombi and venous thrombi.

(thrombi = blood clot)  

arterial thrombi 

- usually begin at site of enothelial injury or turbulence

- grow in retrograde direction from point of attachment

- usually ooclusive, superimposed on antheroslerotic plaue (swelling in artery walls) 

- gray- white and fribale, composed of tangled mesh of plateles, fibrin, RBCs, and degerenateing leukocytes

venous thrombi

- occures in sites of stasis (normal flow of a body liquid stop) 

- extend in direction of blood flow, toward heart

- invaribly occlusive 

- contains more enmeshed RBCs

-affect lower extermities 

changes in vessel wall

alterations in normal blood flow 

changes in blood 

regarding chages in vesell wall as a cause of thrombosis:

affects arteris or veins?

describe actue and chronic injuries

arteris

acute injuries: trauama or surgery, inflammation, lack of blood supply 

chronic injruy: more common -> atherosclerosis

atherosclerosis:

- characterized by thickening of loss of elastiicty of aterial walls due to intimal lesions (intermost layer of artery or vein), atheromas (artery wall thickens), that protude into and obstruct vascular lamina, weaken the underlying media and may undergo serious complicatiions 

-princiaply affects large artieres

-claincal significance:

- can cause:

- symptomatic atherosclerotic disease involing arteries supply the heart (mycardial infraction_, brain (cerebral infarction), kidneys (aortic aneurysms) and lower extremeites (peripheral vascular disease)

-compromise of blood flow in smaller arteries, leading to ischemic injury in distal organs

- thrombus formation that further obsturcts blood flow

- aneurysm foramtion, due to weakening of vessel walls

- embolsim

alterations in normal blood flow (a cause of thrombosis) effects the arteries or veins? 

what effect does turbulence have?

thrombisis induced by slowing of blood stream more common where?

both trubulence and stasis favour thrombis by:

veins 

trubulence: causes endothelial injury or dysfunction and forms counter currects and local pockets of stasis (normal flow of a body liquid stops), a major factor in development of venous thrombi

induced by slowing of blood stream 

more common in veins

trublence and stasis favour thrombosis by:

- disrupting laminar flow and brining platelets into contact with endothelium

- preventing dilution of actiavted clotting factors by fresh flowing blood

- retarding inflow of clotting factors inhibitors and  permitting build up of thrombi

- promoting endothlial cell activation, predispoing local thrombosis, leuckcyte adehsion, ect. 

changes in blood (hyperqualability) happens mostly to veins or atteries?

things that icnrease viscotiy of blood or alters normal balnace of clotting and fibrinolytic mechanisms aids or weakens thrombosis?

describe the roles of polychthemia and hypercoagulability

veins

aids

polycythemia

- increased number of RBCs -> increased viscocity of blood

- contriubtues to small vessel stasis 

- 1o polychthemia: increase in total RBC mass as result of autonomous proliferation of myeloid stem cells (granulocyte precursor cell in bone marrow)

- 2o polycythemia: RBC progenitors are normal but proliferate in response to increased levels of eythropoietin

- appropriate physicologycal polycthemia: deficient oxygenenation of blood 

- inappropriate: non physioloigcal increase in erythroproetin levels are seen with certain renal tumours (place of its secretion) and use of endurance athletes 

Hypercoagulatbility

- is any alteration in balance of clotting and fibrinolytic mechanisms which favour thrombosis. 

- genetic causes: mutations in factor V or prothrombin; deficiens in antithrombin III, proeins S or C

- acquired causes: immoblization, heart attack, tissue damage cancer, prothetic cardiac valves. Pathogensisis 

propagation: accumulation of increased platelets, eventually obstructing some critical vessel 

embolization: dislodging and trasport to other sites in vasculature  

dissolution: removal by fibrionlysis

organiztion and recanalization: inflammation and fibrosis, then reestablisment of blood flow OR incorption into a thickned vascular wall 

- causes obstruction of arteris and veins

- possible soruce of emboli (detached intravascular mass capable of clogging arterial capillary into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body) 

what is an embolism? 

describe an embolous which starts in the vein. 

describe and embolous which orginates from thrombus (99%) in left AV valve. 

list the other sources of embolous. these sources cause? 

a free floating intravascular solid, liquid, or gaseous mass that is careid by blood to site different from its origin 

an embolus that orginates in vein will embolize in vascular bed in lung. ocurs because it suualyl comes up from lower extremities and carried up, passing through right side of heart into pulmonary vasculature

an embolous hwich orginates from thrombus in left AV valve coule emboize to vartiery of sites, deping on relative blood flow. mostly goes to lower extremeites (75%) and brain (10%)

other srouces: ulcerated atheroscletoric plaques, aotric aneruysms, fragmentation of valvaular vegaetion. all cause ifnraction of tissue in distrubtion of obsturcted vessel. 

fractures of long bones (Fatty marrows), soft tissue truama or burns, sever skeleteal injuries. microemboli cause occlusion of microvasculature; FFAs cause local toxic injury to enothelium 

how do air embolisms occur?

what is decompression sickness?

obstetric procues or as consequnce of chest wall injury. need > 100 mL of air to prouce clinical effect.

- affects both major and minor vasculautre. 

decompression sickness: exposure to sudden change in atmospheric pressure. formation of gas baububle with sketal muscle and supporting tissue 

-tear in placental membrane and rupute uterine veins 

- progresses into pulmonary edema + changes of diffuse alveolar damage.

clinical blockage of aterial lumen, preventing blood from reaching the tissue.

effects depend on:

- size of embolus, availibity of colleteral circulation and vulnerability of tissue to ischemia 

1. widespread fibrin depostion -> widespread impaired tissue perfusion -> tissue hypoxia -> ischemia of vulnerable organs (microinarction) + hemolysis of RBCs (chronic DIC)

2. bleeding diathesis (abnormal propensity toward bleeding) -> fibrinolysis due to Pas -> hemostiatic (stops bleeding) failure (acute DIC)

- anaphylaxis:(alergic reaction) immunoglobin hypersenivity

- neurogenic: from spinal cord injury

- septic: microbial infection

- widespread vasoilation -> increased capacity of vascular bed -> decreased HP -> tissue hypoperfusion

thrombogenic substances including:

- shed fetal skin cells

- lanugo hair

- fat

- mucin