Path Week 3: Hemodynamic Disorders, Thromboembolic Disorders, And Shock

Front 1

Edema

Back 1

Increased fluid in interstitial spaces (normally 1/3 of body fluid is in interstitium)

Front 2

Anasarca (hydrops)

Back 2

Severe generalized edema with sub Q swelling.

Front 3

General causes of edema

Back 3

1) Increased hydrostatic pressure forces fluid out of vessels occurring with reduced venous return
2) Decreased plasma osmotic pressure reduces movement of fluid into vessels
3) Lymphatic obstruction blocks removal of interstitial fluid
4) Sodium and water retention
5) Inflammation causing increased permeability with hyperemia (increased blood flow) and endothelial leakiness.

Front 4

Localized vs general increases in hydrostatic pressure leading to edema

Back 4

Localized - DVT causes impaired venous return and edema of effected leg.
General - Congestive heart failure causes:
-Especially of right ventricle causes decreased cardiac output > decreased venous return > increased capillary hydrostatic pressure
-Causes renal hypoperfusion leading to increased aldosterone secretion and ultimately salt and water retention increasing chance for edema.

Front 5

Right vs left ventricle failure with regards to edema

Back 5

Right vent failure - Pitting edema of the extremities; usually legs, sacrum
Left vent failure - Pulmonary edema. Results in heavy lungs with frothy pink fluid at autopsy.

Front 6

What can cause decreased plasma albumin leading to edema

Back 6

1) Nephrotic syndrome - Protein leaks from glomeruli leading to generalized edema
2) Liver disease reduces albumin synth
3) Protein malnutrition " " ".

Front 7

What can cause lymphatic obstruction leading to edema?

Back 7

1) Filariasis can cause lymphatic fibrosis leading to edema of legs and external genitalia (elephantitis)
2) Post breast cancer, metastasis to lymph nodes can lead to edema of arm and peau d'orange appearance.

Front 8

How does inflammation cause edema

Back 8

Permeability causes loss of protein to the interstitium and inflammation also increases blood flow to the area.

Front 9

Clinical effects of edema

Back 9

1) Impairs wound healing and clearance of an infection
2) Pulmonary edema can be fatal due to impaired gas exchange and fluid can act as a great place to grow infection
3) Brain edema can compress vascular supply and herniate brain through foramen magnum.

Front 10

Hyperemia

Back 10

Active augmented flow due to arteriolar dialation (ex inflammation or excersize). Tissue becomes wet and red due to engorgement with oxygenated blood.

Front 11

Congestion

Back 11

Passive, due to impairment of of outflow from a tissue, due to cardiac failure or venous obstruction. Tissue is blueish red due to deoxygenated blood.

Front 12

Acute congestion

Back 12

Lung - Engorged caps, septal edema, and transudate in airspace.
Liver - Central vein and sinusoids swell, central hepatocytes degenerate. Periportal hepatocytes fair better due to proximity to hepatic arterioles.

Front 13

Transudate

Back 13

Ultrafiltrate of blood extravascular fluid with low protein content. Specific gravity of 1.012.

Front 14

Chronic Congestion

Back 14

Occurs with heart failure:
Lung - Hemosiderin-laden macs appear brown. Known as heart failure cells and are a key characteristic. Also have Edemous and fibrotic septa and congested vessels causing rupture.
Liver - Nutmeg liver = Central regions of lobules are red brown against a background of regular tan liver. Central part of lobules are last to recieve blood flow causing centrilobular necrosis. Also occurs during shock.

Front 15

Hemorrhage

Back 15

Extravasation of blood into the extravascular space.

Front 16

Hematoma

Back 16

Hemorrhage enclosed in a tissue.

Front 17

Petechiae

Back 17

1-2 Hemorrhage in skin, mucus membrane or serosa:
1) Local increased intravascular pressure
2) Throbocytopenia or defective platelets
3) Clotting factor deficiency

Front 18

Purpura

Back 18

3-4mm Hemorrhage. Petechia associations as well as:
1) Tramua
2) vasculitis
3) Increased vascular fragility as in amyloidosis

Front 19

Ecchymoses

Back 19

1 or more cm sub Q hematoma (bruise) associations same as purpura.

Front 20

Hemostasis definition and steps

Back 20

Hemostasis is a clot that forms after vascular injury:
1) Reflex after endothelial loss + secretion of endothelin cause vasoconstriction
2) Primary hemostasis - Endothelial cells express von willebrand factor causing platelet adhesion. Platelets activate by changing shape and secreting factors causing other platelets to aggregate forming a plug.
3) Secondary hemostasis - Tissue factor works with platelet secretions to activate thrombin. Thrombin converts fibrinogen to fibrin creating meshwork. Thrombin induces platelet recruitment. All this forms a permanent plug.

Front 21

What are the counterregulatory mechanisms to hemostasis?

Back 21

Released form the endothelial cells:
1) t-Pa - fibrinolytic
2) Thrombomodulin - interferes with coagulation cascade

Front 22

Thrombus vs clot

Back 22

Thrombus - Intravascular coagulation occurring in flowing circulation. Attached to the vessel wall, and has Lines of Zahn - alternating layers of pale platelets and fibrin and dark layers of red cells (usually found in heart/aorta)
Clot - Forms external to circulation or in vessels post mortem (not attached to wall). Has dark red area which looks like current jelly made of red cells and a yellow layer which looks like chicken fat from clotted plasma.

Front 23

3 things which predispose you to a thrombus

Back 23

Endothelial injury (biggest), abnormal blood flow, and hypercoaguability.

Front 24

Why would abnormal flow increase risk for a thrombus?

Back 24

Disruption of laminar flow leads to:
1) Brings platelets into contact with endothelium
2) Prevents dilution of activated clotting factors by flowing blood
3) Retards incoming flow of clotting factor inhibitors
4) Permits buildup of thrombus
5) Promote endothelial cell activation (can actually alter endothelial gene expression)

Front 25

Aneurysm

Back 25

Abnormal dilation of an artery or heart.

Front 26

What are clinical causes of abnormal flow?

Back 26

1) Stasis (via varicose veins, aneurisms, or MI)
2) Atherosclerotic plaques
3) Vessel injury via trauma, surgery, burns, Bed Rest.
4) Atrial fibrillation
5) Hyperviscosity syndromes increase resistance to flow and cause stasis in small vessels (polycythemia, sickle cell)

Front 27

Thrombophilia

Back 27

Hypercoagulability

Front 28

Examples of primary (genetic) causes of hypercoagulability

Back 28

1) Factor V mutations cause resistance to activated protein C, a antithrombotic factor
2) Mutations in prothrombin gene
3) Deficiency of anticoagulants: antithrombin 3, protein C, or protein S
4) Elevated homocysteine

Front 29

Examples of secondary (acquired) causes of hypercoaguability

Back 29

1) Prolonged bed rest/immobilization
2) Atherosclerosis leading to high levels of lipoproteins interfering with fibrinolysis
3) Cancer which can cause procoagulant tumor products.
4) Pregnancy increases production of platelets and clotting factors and decreases production of anti.
5) Autoimmune disorders leading to secondary antiphospholipid syndrome
6) Increased platelet stickiness in morning
7) Smoking
8) Surgery associated with increases in fibrinogen

Front 30

Arterial thrombi morphology

Back 30

1) Begin at site of endothelial injury or turbulence (atherosclerosis) and grow towards the heart
2) Usually grey/white
3) Sites: coronary artery > cerebral > femoral artery

Front 31

Mural thrombi

Back 31

Nonocclusive thrombi attached to the wall of heart or aorta. Often at the sire of aneurysm

Front 32

Vegetation

Back 32

Thrombus on a cardiac valve

Front 33

Phlebothrombosis

Back 33

Venous thrombi

Front 34

Venous thrombi morphology

Back 34

1) Occurs with stasis, grows towards the heart
2) Occlusive
3) Forms red-blue cast of vein lumen with strands of pale fibrin
4) Sites: Deep leg vein > upper extremities > periprostatic plexus, ovarian veins

Front 35

Superficial vein thromboses

Back 35

Rarely embolize but local edema and impaired drainage predisposes to infection and varicose ulcers known as stasis dermatitis.

Front 36

DVT

Back 36

Deep vein thrombosis. Are especially dangerous b/c can embolize and to lungs and lead to death.

Front 37

The Four Fates of the Thrombosis

Back 37

1) Propagation - Accumulation of platelets and fibrin leads to complete obstruction
2) Dissolution - Removal via fibrinolytic activity. Almost never happens with older thrombi. Can be induced therapeutically via t-PA for a coronary thrombosis but must be given soon after thrombus.
3) Organization and recanalization - Inflammation and fibrosis can lead to creation of channels which reestablish flow.
4) Embolization - Dislodges and travels to other sites.

Front 38

Types of emboli

Back 38

1) Pulmonary thromboembolism (PE)
2) Systemic Arterial thromboembolism
3) Fat embolism
4) Gas embolism
5) Amniotic fluid embolism
6) Injected things by drug users
7) Clusters of tumor cells

Front 39

Result of a PE

Back 39

Can cause sudden death, right ventricular failure, or shock. If 60% or more of pulmonary blood flow is cut off, patient will suddenly die. After one PE, patient is at higher risk for more.

Front 40

Characteristics of a PE

Back 40

1) Usually occlude pulmonary artery at bifurcation (saddle embolus) or in smaller arteries
2) Does not usually cause infarction (b/c of bronchial circ) unless also have left sided cardiac failure.
3) Multiple small emboli over time can cause pulmonary hypertension and right vent failure.
4) Can cause paradoxical embolus - If patient has a septal defect in heart, can pass into systemic circulation (even though DVT usually go to lungs).

Front 41

Systemic arterial thromboembolism

Back 41

Come from intracardiac mural thrombi, atherosclerosis, and aortic aneyurisms. Can lodge anywhere; Lower extremities > Brain > intestine, kidney, and spleen.
Can cause an infarction.

Front 42

Fat embolism syndrome

Back 42

Caused by a fat embolism during long bone fracture, soft tissue trauma, or burn. Fat from marrow gets into blood. Mechanical obstruction and endothelail injury due to free fatty acids can lead to occlusion of cerebral caps and hemorrhages in the brain. Can also lead to pulmonary problems or thrombocytopenia and petechia.

Front 43

What causes a gas embolism

Back 43

During obstetric or laproscopic procedures, chest wall trauma, or decompression sickness. Need 100cc of air for effect.

Front 44

Decompression sickness

Back 44

AKA the bends, caused by sudden change in atmospheric pressure to divers and astronauts. High pressure dissolves nitrogen gas, low pressure allows it to go back to gasseous state leading to gas embolism.

Front 45

Caisson disease

Back 45

Chronic decompression sickness.

Front 46

Cause/presentation of amniotic fluid embolism

Back 46

Caused by amniotic fluid and contents entering mother circulation b/c of utterine vein rupture. Very Fatal.
Presents with severe dyspnea, cyanosis, hypotension, coma, pulmonary edema, and DIC (disseminated intravascular coagulation)

Front 47

What organs are usually the target of an arterial infarct vs a venous?

Back 47

Arterial - heart, brain, lungs, and intestine.
Venous - Occurs in organs with only one venous outflow; testes, ovary.

Front 48

Red Infarction

Back 48

Occurs with:
-Venous obstruction where theres only one venous supply (testes, ovaries)
-Arterial occlusion in tissue which have spaces to accumulate fluid in infarcted areas (lung, intestine)
-Arterial occlusion where there is dual circulation allowing blood to get to the necrotic areas (lung, intestine)
-Places where there is a temporary occlusion followed by reflow to the necrotic region (brain).

Front 49

White Infarction

Back 49

Occurs with arterial thrombosis, embolism, or block in blood to a solid organ that dosent leave space for blood to collect.
Typically wedged shaped as damage occurs to a trunk and its tributaries. Damage leads to scar tissue (except in brain which gets liquefactive necrosis)

Front 50

Septic vs Bland Infarction

Back 50

Septic - Infectious agents are present. infarction has prominent inflammatory response.
Bland - No infectious agents.

Front 51

Factors that influence the development/damage of an infarct

Back 51

1) Nature of vascular supply. Dual and anastomosing supplies protect against infarcts. Being an end arterial like kidney and spleen hurts.
2) Rate of development of the occlusion. If develops slowly, blood can create collateral circulation and protect itself.
3) Vulnerability to hypoxia. Neurons die in 3-4 mins post ischemia, heart 20-30 mins, fibroblasts, 1-2 hours
4) Oxygen content of blood. Partial obstruction in an anemic/cyanotic patient can lead to tissue infarction.

Front 52

Important organs with dual blood supply

Back 52

Lungs and liver

Front 53

Important anastomosing circulations

Back 53

-Radial and ulnar arteries
-Circle of willis
-Small intestine

Front 54

Shock Definition

Back 54

Systemic hypoperfusion due to decreased cardiac output or circulating blood volume.

Front 55

Types of shock

Back 55

1) Cardiogenic - MI, Myocarditis, Cardiac temponade, Pulmonary embolism
2) Hypovolemic - Hemorrhage, diarrhea, dehydration, burns
3) Sepsis
4) Anaphylactic from type 1 hypersensitivity Rx
5) Neurogenic via brain damage or spinal chord injury

Front 56

Clinical stages of shock

Back 56

1) Non-progressive stage - Compensation w/ tachycardia and vasocontriction keep heart and brain perfused, but skin becomes cold
2) Progressive stage - Tissue hypofusion occurs with acidosis, decreased urine output, confusion
3) Irreversible stage - Cellular injury is so severe that even if hemodynamic problems could be fixed, survival still wouldnt be possible.

Front 57

Effects of shock on body and organs

Back 57

Get fever, tachycardia, leukopenia due to TNF, IL-1, and IL-6:
Brain - Hypoxic ischemic encephalopathy
Heart - Coagulation and contraction band necrosis, subendocardial hemorrhage.
Kidney - Acute tubular necrosis
Lungs - Diffuse alveolar damage (Aka shock lung, a type of ARDS)
GI - Hemorrhagic enteropathy
Liver - Acute centrilobular necrosis and congestion.
DIC - Disseminated intravascular coagulation w/ thrombotic microangiopathy. Coagulation factors are depleted from all the microthombi being formed in small vessels. Once coag factors are depleted, uncontrolled hemorrhage ensues.

Front 58

Circulating cells involved in acute inflammation

Back 58

Neutrophils
Eosinophils
Basophils

Front 59

Circulating cells involved in chronic inflammation

Back 59

Lymphocytes
Plasma cells
Monocytes

Front 60

Neutrophil microscopic appearance

Back 60

Clear with multi-lobular nucleus with strands of nucleus connecting lobes.

Front 61

Eosinophil microscopic appearance

Back 61

Eosiniphilic granules with a bi-lobular morpheus glasses looking nucleus

Front 62

Lymphocyte microscopic appearance

Back 62

Large round nucleus with little cytoplasm

Front 63

Plasma cell microscopic appearance

Back 63

More cytoplasm than lymphocyte with ascentric clock face nucleus

Front 64

Monocyte vs mac

Back 64

Monocyte = in circulation
mac = out of circulation

Front 65

Mast cell microscopic appearance

Back 65

Not going to be present in circulation, will in bone marrow and tissue. Look super basophilic like a basophil

Front 66

What does a mast cell contain

Back 66

Heparin and histamine

Front 67

Histiocyte

Back 67

Type of macrophage which is in a tissue

Front 68

Abscess

Back 68

Focal localized deep collection of purulent inflammatory tissue

Front 69

Granuloma

Back 69

Circumscribed collection of epithelioid histiocytes, can have surrounding collar of lymphocytes and can have giant cells.

Front 70

Epithelioid Histiocyte

Back 70

Histiocyte which looks like a columnar epithelial cell. Important in granulomatous inflammation.

Front 71

What are some causes of granulomatous inflammation

Back 71

1) Mycobacteria (TB)
2) Parasites
3) Fungus
4) Foreign body
5) Sarcoidosis

Front 72

What color is necrosis tissue

Back 72

Red is dead.

Front 73

Dysplasia

Back 73

Change in organization of a tissue

Front 74

What color is neoplastic tissue

Back 74

Blue is bad. Occurs b/c of an increase of nucleus to cytoplasm ratio.

Front 75

"Adeno" tumor

Back 75

Glandular epithelial tumor

Front 76

Sarcoma tumor

Back 76

Mesenchymal (fat, muscle)

Front 77

In-situ tumor

Back 77

Still confined by the basement membrane. Probably wont metastitize.

Front 78

Infiltrating tumor

Back 78

Tumor which has broken through the basement membrane

Front 79

Anaplasia

Back 79

Tumor cells which no longer have characteristics of their cell of origin. Found in poorly differentiated tumors.