Week 2

Question 1

The accumulation of fluid in the tissues is called ___ and the accumulation of fluid within a body space or cavity is called an ___

An ___ hydrostatic pressure or ___ colloid osmotic pressure results in net fluid movement out of the vessel into the surroundings and if the lymphatic system can’t control it, then edema or effusions occur

Answer 1

Edema, effusion

High, Low

Question 2

Remember, edemas and effusions from an inflammatory response results in an ____ (a fluid high in protein content and maybe some cells) due to the increased vasodilation/stasis and increased interendothelial spaces

Non-inflammatory edema and effusions are protein poor fluids and called ___

Answer 2

Exudate

Transudates

Question 3

Common causes for edema and effusion transudate to occur include

1) Venous outflow obstruction (congestive heart failure) which would increase ___ pressure
2) Liver diseases (like liver cirrhosis or ascites) and kidney diseases (like nephrotic syndrome) or malnutrition can lead to decreased protein synthesis or protein loss (with the MAIN protein being ___) and this would cause a decrease in ___ pressure
3) ___ and ___ retention which would increase hydrostatic pressure (due to intravascular fluid volume expansion) AND decrease colloid osmotic pressure (due to dilution). This problem occurs in ___ failure and is often seen in congestive heart failure, which results in decreased blood flow to the kidney (renal hypoperfusion), which then goes on to activate the renin-angiotensin-aldosterone system and this increases Na+ and H2O reabsorption and increases renal perfusion aka blood volume (at first this is what we want, but if heart continues to fail, retained fluid turns into edema)
4) ___ obstruction from trauma, fibrosis, invasive tumors, and infectious agents that leads to lymphedema

^** Parasitic filariasis causes fibrosis and results in elephantiasis

Answer 3

1) Hydrostatic
2) Albumin, osmotic
3) Salt and water, renal
4) Lymphatic

Question 4

Edema is most common in subcutaneous tissue, the lungs, or the brain

Subcutaneous edema can be diffuse or more conspicuous in regions with high hydrostatic pressures and is often influenced by gravity (would appear in the legs while standing or sacrum while sitting) called ___, and if you put pressure into it, you can displace the interstitial fluid called a ___

*** Subcutaneous edema can also signify ___ or ___ diseases and if there is edema in the ___ region (a part of the body such as the eyelids that contain loose connective tissue), it is a __ dysfunction.

Pulmonary edema is commonly a secondary cause from congestive heart failure and the lungs are 2-3 times their normal weight and sections yielding frothy, blood-tinged fluid (a mixture of air, edema, and extravasated red cells)

Brain edemas have narrow sulci and distended gyri

Answer 4

Dependent edema, pitting edema

Renal or cardiac, periorbital, renal

Question 5

Effusions in the pleural cavity (lungs) is called a ___, in the pericardial cavity (heart) it is called a ___, and in the peritoneal cavity (often seen in liver diseases) it is called ___

___ effusions are translucent and straw colored (since they are protein poor)

___ effusions are cloudy (since they are rich in proteins and often have white cells)

Answer 5

Hydrothorax, Hydropericardium, Hydroperitoneum aka *Ascites **

Transudate

Exudate

Question 6

The process of arteriolar dilation leading to increased blood flow to a given location is called ___ and the tissues show ___ due to the increased delivery of oxygenated blood

^** Example includes excersice or inflammation

A passive process leading to reduced outflow of blood from a tissue is called ___, and since the blood is not getting out of the tissue, it causes an ___ in hydrostatic pressure, leading to edema and in chronic cases, it can lead to ___ and ischemia

^** Example includes local obstruction or congestive heart failure

Answer 6

Hyperemia, erythema

Congestion, increase, hypoxia

Question 7

___ tissue takes on a “dusky” reddish-blue color (cyanosis) due to red cell stasis and deoxygenated hemoglobin levels

In ___ congestion, engorged alveolar capillaries, alveolar septal edema, and focal intraalveolar hemorrhage occurs

In ___ congestion, septa are thickened and fibrotic, alveoli contain numerous hemosiderin-laden macrophages called ___ cells

In ____ congestion, central vein and sinusoids are distended

In ___ congestion the centrilobular regions are red-brown and slightly depressed and are accentuated against surrounding zones of an uncongested tan liver called a ___ liver

^** Microscopically, there is centrilobular hemorrhage, hemoisiderin-laden macrophages, and a variable degree of hepatocyte dropout and necrosis

Answer 7

Congested

Acute pulmonary

Chronic pulmonary, heart failure

Acute hepatic

Chronic hepatic, nutmeg

Question 8

___ is the process by which blood clots form at sites of vascular injuries and disorders such as hemorrhagic disorders (excess bleeding since hemostasis isn’t working) or thrombotic disorders (blood clots since hemostasis is working to much)

The formation of a blood clot goes as follows

1) The release of ___ causes arteriolar vaso___
2) Primary hemostasis occurs due to disruption of the endothelium, which exposes __ factor and ___, which promote platelet adherence and activation (the platelets change shape and also release secretory granules to recruit more platelets) and these undergo aggregation to form the plug
3) Secondary hemostasis occurs when ___ is exposed at the site of injury and this activates factor ___, which leads to ___ generation that cleaves fibrinogen into ___ to create an insoluble meshwork
4) Clot stabilization and resorption occurs and a solid plug forms to prevent further hemorrhage

^** At this stage, counter regulatory mechanisms are displayed to limit clotting at the site such as ___, which aids in fibrinolysis and thrombomodulin to block coagulation cascade

Answer 8

Hemostasis

1) Endothelin, vasoconstriction
2) vWF (Von Willebrand Factor) and Collagen
3) Tissue Factor, VII, thrombin, fibrin
4) t-PA (Tissue plasminogen activator)

Question 9

Platelet function depends on their several glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules including

1) ___ granules which has the adhesion molecule __-selectin on their membrane and contain coagulation proteins like fibrinogen, Coagulation factor V, vWF, PDGF, etc…
2) ___ granules contain ADP and ATP, Ca2+, serotonin, and epinephrine

Answer 9

1) Alpha, P

2) Delta

Question 10

Platelet adhesion, like we already said, occurs when vWF and collagen is exposed and the platelet surface receptor ___ binds to these

Now that the GpIb-vWF has allowed for platelet adhesion to occur, they are activated by changing shape and releasing granules

1) Changing shape increases surface area and translocates ___ charged phospholipids (Phosphatidylserine) to the platelet surface to bind ___ and serve as nucleation sites for the assembly of coagulation factor complexes
2) Secreting granules such as ___ allows the conformational shape change to occur, and ___ is needed for additional platelet aggregation and activation (remember, COX is needed for this)

As aggregation occurs, the platelet ___ receptors binding to ___ allow the primary hemostatic plug to form

As hemostasis continues, a cascade of enzymatic reactions occurs and this leads to the formation of ___, which cleaves the fibrinogen into fibrin, which cements the platelets in place to form a secondary hemostatic plug

^** At the same time, the thrombin also continues to further activate platelets via PAR (protease activated receptor) and also continues platelet aggregation and contraction

Answer 10

GPIb (Glycoprotein Ib)

1) Negatively, Ca2+
2) ADP, TxA2

GpIIb-IIIa, fibrinogen

Thrombin

Question 11

The coagulation cascade is divided into 3 pathways, the intrinsic, extrinsic, and common pathways

PT and PTT measure fibrin clotting time in the plasma by assessing the function of the factors involved in these pathways

___ measures the extrinsic pathway and occurs by adding ___, phospholipids and Ca2+
^** Occurs in 10-12 seconds

___ measures the intrinsic pathway and occurs by adding ___, phospholipids, and Ca2+
^** Occurs in 35 seconds

Answer 11

Pt, Tissue factor

PTT, Negatively charged surface (like glass beads)

Question 12

Thrombin has many roles including

1) Activating cross linked fibrin via cleaving ___ and activating factor ___ along with activating other coagulant factors including V (5), VIII (8), and XI (11)
2) Thrombin can activate platelets and inflammation by binding to ___
3) Once normal endothelium is encountered, thrombin changes to have ___ effects

Answer 12

1) Fribrinogen, XIII (13)
2) PARs (protease activated receptors)
3) Anticoagulant

Question 13

There are various factors that limit coagulation including

1) Wash out factors from dilution of blood flowing past the site of injury
2) A need for a ___ charged surface
3) Normal endothelium (**Which is discussed in more detail on another card)
4) Fibrinolysis, aka the breakdown of fibrin, which occurs via cleaving of fibrin by ___ and these produce fibrin split products such as D-dimer that can be used as a marker for several thrombotic states

^** Plasmin is generated from plasminogen via a factor __ dependent pathway (which is why if this is deficient, thrombosis can occur) or ___

Answer 13

2) Negatively
4) Plasmin

XII (12), t-PA

Question 14

Normal endothelium is important for limiting coagulation leading to thrombosis

The antithrombotic properties include

1) Inhibit platelets by shielding them from the subendothelial vWF and collagen along with releasing the prostaglandin ___, the enzyme ___, and ___ all of which inhibit platelet aggregarion
2) Prevents coagulation via shielding coagulation factors from ___ factors and produces ___ and ___ receptor

^** Thrombomodulin and protein C receptor bind both thrombin and protein C, and causes thrombin to cleave protein C (instead of its normal mechanism of cleaving coagulation factors). Now that protein C is cleaved and activated, the cofactor protein __ binds to activated protein C and the complex is an extremely potent inhibitor of ___ and ___

There is also heparin like molecules that activate anti-thrombin 3 (III) that inhibits thrombin/various coagulation factors and also ___ and its cofactor (protein S) inhibit TF/VIIa complex

3) Normal endothelial cells also release ___ to promote fibrinolysis

Answer 14

1) PGI2, Adenosine Diphosphatase (ADPtase degrades ADP that was important for platelet activation), and NO
2) Tissue factors, Thrombomodulin and protein C receptor, S, Va (5) and VIIIa (8)

Tissue factor pathway inhibitor (TFPI)

3) t-PA

Question 15

Defects in ___ hemostasis are associated with platelet defects (like thrombocytopenia) or von Willebrand disease and if the bleed is small (1-2mm) it is called ___ and if it is larger (4-10mm) it is called ___

These primary hemostasis bleeds are associated with ___ bleeding

Various causes can be aquired and some examples include ___ aka low platelet count, renal failure leading to uremia which causes reduced platelet function, or excess ___ intake which can inhibit COX leading to decreased TxA2 and therefore decreased platelet aggregation

Other causes can be hereditary including GpIIb-IIIa deficiency called ___ thrombasthenia, GpIb deficiency called ____ syndrome, or vWF deficiency called von WIllebrand disease

^** Secondary hemostasis defects are involved with coagulation factor defects and often seen in bleeding into soft tissues (muscles) or joints (bleeding into joints is called ___) like in hemophilia

Answer 15

Primary, petechiae, purpura

Mucocutaneous

Thrombocytopenia, Aspirin

Glanzmann, Bernard-Soulier

Hemarthrosis

Question 16

Generalized defects involving small vessels often present with palpable ___ and ___ (small bruises) and these create a mass called a hematoma

^** Often characteristic of disorders that disrupt small blood vessels or lead to blood vessel fragility

Answer 16

Purpura and ecchymoses

Question 17

The Virchow triad is three different mechanisms that can lead to thrombosis and include

1) Endothelial injury. When endothelial cells are injured, they expose vWF and collagen in order to begin coagulation like we have already discussed. The endothelial cells that are injured also shift their gene expression to that of pro-thrombotic mechanisms that results in the downregulation of ___ that causes thrombin to continue activating coagulation factors; down regulation of protein C and TFPI (also anticoagulants); finally, activated injured endothelial cells secrete ___ to inhibit fibrinolysis and down-regulate t-PA expression
2) Abnormal blood flow can lead to endothelial injury (like we just discussed above^) via turbulent flow (in arteries and heart), and it can also contribute to local pockets of ___ (in veins) that is a major contributor to vein thrombosis. It can disrupt laminar flow and bring platelets into contact with the endothelium and prevent dilution/washout of activated clotting factors and prevent the inflow of clotting factor inhibitors

^** Clinical examples include ulcerated atherosclerotic plaques, Aneurysms, Infracted myocardial tissue, and prolonged immobilization

3) Hypercoagulability (also called thrombophilia) which is any disorder of the blood that predisposes to thrombosis

Answer 17

1) Thrombomodulin, PAIs (Plasminogen activator inhibitors)

2) Stasis

Question 18

For hereditary (primary)

Most commonly cause of hypercoagulability among Caucasians that are at an increased risk for DVT is the hereditary ___ point mutation that occurs from a ___ -> ___ substitution and this leads to resistance towards ___ and as a result the anticoagulant pathway is lost

The second most common inherited cause of is a gene mutation for the ___ gene that leads to increased circulating levels of prothrombin

Other hereditary causes leading to hypercoagulability can include homocysteinuria via a deficiency in Cystathione Beta-synthetase or deficiencies in anticoagulant proteins (like protein C, protein S, Antithrombin III, etc)

** ^ Note that genetic hypercoagulable states are ___ and acquired are ___

Answer 18

Factor V Leiden, Gln (Glutamine) -> Arg (Arginine), Protein C

^** In other words, normal is Arginine, but in this mutation Glutamine takes its place

Prothrombin

Primary, secondary

Question 19

For acquired (secondary)

Hypercoagulability (thrombophelia) can occur from lots of different mechanisms like immobilization, MI or A-fib, oral contraceptives, smoking, tissue injury or Trousseau’s syndrome

However, the most important clinical acquired thrombophilias are HIT (Heparin-induced thrombocytopenia) and Antiphospholipid antibody syndrome

HIT is caused from administration of unfractionated heparin which can induce antibodies that can bind to heparin and platelet factor 4 to result in their activation, aggregation, and consumption

___ syndrome is characterized by recurrent vascular thrombosis, thrombocytopenia, and/or recurrent fetal loss and is associated with antibodies to anionic phospholipids

^** This is often associated with autoimmune disorders like lupus and clinical presentation is dependent on the vessels involved (ex: Pulmonary embolism, stroke, MI, bowel infraction, etc)

Answer 19

Antiphiospholipid antibody syndrome (APA)

Question 20

Arterial or cardiac thrombi arise at sites of turbulence and venous thrombi at sites of stasis

^** both grow in the vessel towards the heart

Thrombi are often laminated with lines of ___ which are alternating red (from RBCs) and tan (Platelets and fibrin) regions

Thrombi occurring in the heart chambers or within the aorta are called ___ thrombi and often occur from MI or aortic aneurysms

Thrombi on heart valves are called ___ and can be from bloodborne bacteria or fungi (like in infective endocarditis) or sterile vegitations due to hypercoagulable states (called nonbacterial thrombotic endocarditis)

Arterial thrombi are often occlusive and occur commonly at coronary, cerebral, or femoral arteries

___ thrombi (aka phlebothrombosis) often occur in the lower extremities like in the legs, and contain more red blood cells than platelets and therefore are also called red/stasis thrombi

^** Postmortem clots can be confused with venous thrombi, but they are different due to their gelatinous, dark-red dependent portion and a yellow “chicken fat” upper portion and also not commonly attached to the vessel wall

A thrombus can undergo propagation, embolization, dissolution via fibrinolysis, and organization/recanalization (which replaces the thrombus with fibroblasts, smooth muscle cells, and endothelial cells)

Answer 20

Zahn

Mural

Vegitations

Venous

Question 21

____ is a nonspecific term that is associated with a large number of conditions that results in systemic activation of thrombin due to dysregulation of the coagulation and fibrinolysis systems

This mechanism causes widespread microthrombi by a coagulation cascade being set off; but then it consumes coagulation factors and also consumes platelets, which eventually will now lead to excess bleeding

* The lab values for this show ___ PT, ___ PTT, ___ Fibrinogen, ___ Fibrin degradation products (like D-dimers), and ____ platelet count (also called thrombocytopenia)****

^*** When we say elevated/increased PT and PTT it means that coagulation is taking longer, and this does so because we are using up all the clotting factors

^** Also, Fibrinogen is decreased because we are converting all of it to fibrin for clotting; the fibrin degradation products (d-dimer) is elevated because the increased coagulation -> increased plasmin -> Fibrinolysis -> Fibrin Split products

PG 663

Answer 21

DIC (Disseminated Intravascular Coagulation)

Increased, Increased, Decreased, Increased, Decreased

Question 22

Most coagulation factors are made in the __, so if this is diseased, you get decreased synthesis and therefore elevated PT and PTT

Vitamin __ is also important for many coagulation factors and if this is deficient from being malnourished, prolonged antibiotics, or warfarin-coumadin it can lead to elevated PT and normal PTT

Massive transfusion (1.5 times blood volume in 24 hours) results in dilution of factors and increased PT and PTT (along with decreased fibrinogen and platelets)

Acquired factor inhibitors like antibodies to coagulation factors causing VIII to be inhibited (can occur in B-cell lymphoma/plasma cell neoplasms or amyloidosis) can also lead to problems

Answer 22

Liver

Vitamin K

Question 23

___s are detached intravascular solid, liquid, or gaseous masses that are carried by the blood from its point of origin to a distant site and most arise from thrombus

DVTs can result in ___ embolization (Through venous system -> right side of heart -> pulmonary arteries)

Most PEs are small and silent, if 60% or more of the pulmonary circulation is disrupted, the ___ heart will fail and multiple small emboli can eventually lead to pulmonary HT and subsequent right heart failure

Answer 23

Embolism

Pulmonary

Right

Question 24

Most systemic emboli occur from ___ and the majority go to the lower extremities or the brain

^** Associated with the __ ventricular wall infract or left atrial dilation and fibrillation

Other causes of systemic emboli include aortic aneurysms, valvular thrombi, or atherosclerotic plaques

Answer 24

Intracardiac mural thrombi (aka from the heart)

Left

Question 25

Fat and marrow embolisms can be found in the ____ vasculature after trauma (most often bone fractures) that translocates marrow/fat globules into the venous sinuses and then to the lungs

Most of the time it is subclinical, but it sometimes can turn into a fat embolism syndrome and is characterized by pulmonary insufficiency (dyspnea, tachypnea, or tachycardia), neuologic symptoms (irritability, delirium, or coma) and ___ platelet count (thrombocytopenia) due to platelets adhering to fat globules and ___ due to red cell aggregation and/or hemolysis

^** Also a diffuse ___ is related to rapid onset of thrombocytopenia
^** So you can see a petechial rash in a fat embolism

In amniotic fluid embosisms, they are associated with the previous development of ___

Answer 25

Pulmonary

Decreased, anemia

Petechial rash

DIC

Question 26

Remember, an ___ is a discrete area of ischemic necrosis, specifically ___ necrosis (except in the brain it is ___ necrosis), caused by vascular occlusion

___ thrombosis or embolisms underly the vast majority of infractions

There are two types of infracts

1) ___ infracts occur in tissues with dual blood supplies (like the lung), venous occlusions (like in testicular torsion), previously congested tissues by sluggish venous outflow, reperfused necrotic tissue after arterial occlusion
2) ___ infracts occur in solid organs with end-arterial circulation like the heart, spleen, and kidney

^** So just to recap, the lungs would have ___ infracts and the heart/spleen/kidney would have ___ infracts

Answer 26

Infract, coagulative, Liquefactive

Arterial

1) Red (Hemorrhagic)
2) White (anemic)

Red, white

Question 27

Infected cardiac valve vegitations can break off and embolize or necrotic tissue can become infected; both leading to a ___ infract and in this type of infract it is eventually converted to an ___with a correspondingly greater inflammatory response

Answer 27

Spetic, abscess

Question 28

Shock decreases tissue perfusion and results in hypoxia if not corrected

There are three classifications of shock including

1) ___ shock results from low cardiac output due to myocardial pump failure resulting from intrinsic myocardial damage, extrinsic compression, or obstruction to outflow
2) ___ shock occurs due to low cardiac output from low blood volume or plasma volume (Aka fluid loss like from hemorrhage, vomiting, diarrhea, etc)
3) Shock associated with systemic ___ like ___ shock which is associated with microbial infection

Answer 28

1) Cardiogenic
2) Hypovolemic
3) Inflammation, septic

Question 29

The most common cause of death due to shock is ___ shock caused by many organisms with the most prevalent being Gram + bacteria

Septic shock pathogenetic factors include PAMPs (Pathogen associated molecular patterns) from the bacteria being recognized by complement and TLRs for innate immunity leading to TNF, IL-1, etc and therefore increased endothelial activation and injury leading to vasodilation (decreased blood pressure) and increased permeability (leakage and edema and eventually stasis)

Also the PAMPs activate Factor XII, which leads to procoagulants activated (systemic increase in thrombin due to increased Tissue Factor and decreased TFPI/Thrombomodulin/Protein C)

Septic patients also exhibit metabolic disturbances including ___ resistance and ____gylcemia

In the end, organs are damaged due to accumulated damage, secondary to hypoxia via decreased blood pressure, interstitial edema, stasis, and small vessel thrombosis

^** DIC is also seen in septic shock

Answer 29

Septic

Insulin, hyperglycemia

Question 30

Septic shock mechanisms are still unclear other than the fact that organ failure secondary to edema and the attendant tissue hypoxia has a critical role

However, cardiogenic and hypovolemic shock evolve through three general phases

1) An early ___ phase is characterized by neurohumoral compensatory mechanisms like sympathetic discharge leading to catecholamine releases or renal conservation of volume via baroreceptors, etc.

^** The net effect is tachycardia, peripheral vasoconstriction, and renal conservation of fluid

2) The ____ stage is characterized by tissue hypoperfusion, widespread hypoxia, and onset of worsening circulatory and metabolic disturbances like lactic acidosis (aka aerobic to anerobic metabolism and further vasodilation and peripheral pooling and stasis) leading to the beginning of vital organ failure
3) The ___ stage results in lysosomal enzyme leakage and eventually death

In other words, cellular and tissue changes induced by cardiogenic or hypovolemic shock are essentially those of ___ injury

Answer 30

1) nonprogressive
2) progressive
3) irreversible

Hypoxic

Question 31

The ___ changes in shock are seen in all forms of stress and results from cortical cell lipid depletion

The ___ exhibit acute tubular necrosis

The lungs are ONLY affected in pure ____ shock since they are resistant to hypoxic injury

Diffuse alveolar damage can be seen in patients suffering ___ shock or trauma and can also lead to petechial hemorrhages on serosal surface and the skin

__ shock is normally cool, clammy, and cyanotic

___ shock is normally warm and flushed

^**Both can present with hypotension and tachycardia

Answer 31

Adrenal

Kidneys

Hypovolemic

Septic

Cardiogenic/hypovolemic

Septic