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MOD 1: DR > Chapter 4 > Flashcards

Chapter 4 Flashcards

1
Q

What is edema?

A

abnormal accumulation of fluid in the interstitial space (outside of the cells) d/t disorders that disturb the function of the heart, kidneys or liver.

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2
Q

What is effusion?

A

abnormal accumulation of fluid in body cavities (potential spaces) lined with serosal membranes. These spaces include: pleural space, pericardial space, joint space and peritoneal space

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3
Q

What 4 places can effusion occur in?

A

1. Pleural space (hydrothorax)

2. Pericardial space (hydropericardium)

3. Joint space

4. Peritoneal space (hydroperitoneum; ascities)

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4
Q

Effusion inside the peritoneal space is called what?

A

Ascites

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5
Q

The fluids of edema and effusion can be categorized as what and can be ________ or _______.

A

inflammatory or noninflammatory

localized (d/t venous or lymphatic obstruction) or systemic (d/t heart failure)

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6
Q

What is the difference between inflammatory and non-inflammatory related edema/effusion?

A

Inflammation-related edema and effusion:

  • protein rich (exudate) due increased vascular permeability caused by inflammatory mediators
  • Typically localized to a local area, but can also be systemic when the pt has sepsis

Noninflammatory edema and effusion:

  • protein poor fluid (transudate) that is common in diseases that affect the pressures of the vascular system.
  • Ex. <3 failure, liver failure, renal dz, nutritional disorders.
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7
Q

How do we normally prevent edema and effusion?

A
  • Normally; the balance of fluid movement is kept equal;
    • an increase in hydrostatic pressure pushes fluid out or decrease in colloid osmotic pressure => increase in interstitial fluid.
    • If the amount of fluid in the interstial space > lymphatic drainage
    • => fluid will accumulate.
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8
Q

What are the causes of non-inflammatory edema (4)

A
  • 1. Increased hydrostatic pressure
  • 2. Reduced plasma oncotic pressure
  • 3. Na and Water Retention (often d/t renal failure)
  • 4. Lymphatic obstruction
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9
Q

Describe how increase hydrostatic pressure => non-inflammatory edema

A

Forces fluid out and is most often d/t impaired venous return (congestion). Increased hydrostatic pressure can be localized (ex DVT) or systemic (CHF; causes a wide-spread increase in hydrostatic pressure). This can occur by 3 mechanisms:

  1. Congestion* => passive PATHOLOGICAL CONDITION where not enough blood is leaving, causing a backup of venous blood in the capillary beds => fluid leaks out.
  2. Na/H20 rentention => the overall volume
  3. Hyperemia => active physiological arterial condition where arterial dilation=> too much oxygenated blood is arriving at the tissue => tissue turns red
    1. This can be controlled by pre-capillary sphincters, which maintain appropriate pressure.
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10
Q

What 3 mechanisms can cause increased hydrostatic pressure, which leads to edema?

A
  1. Congestion=> a passive pathological condition where blood is not leaving, causing a backup of VENOUS blood. This venous blood increases hydrostatic pressure => leaks out => edema
  2. Hyperemia=> a active physiological condition where too much oxygenated arterial blood is arriving in normal conditions d.t dilation. This is controlled by pre-capillary sphincters, which help to maintain app pressure. Ex. is running => incrase BF to face
  3. Na and H20 retention => nicreases overall volume
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11
Q
  • A passive pathological condition where not enough blood is leaving, causing a backup of venous blood in the capillary beds.
    • As a result, fluid leaks out of the BV -> edema,
    • Is this condition local or systemic?
A

Congestion

Can be local or system

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12
Q
  • a physiological arterial condition where too much blood is arriving at the tissue d/t dilation -> causing tissue to turn red
  • Is this condition local or systemic?
A

Hyperemia

Condition can be both

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13
Q

Describe how reduced plasma oncotic pressure => non-inflammatory edema.

A
  • In normal circumstances, albumin accounts for almost half of the total protein in the plasma. It wants to keep fluid in.
  • Decrease albumin => decrease oncotic pressure .
  • Loss of albumin and decreased plasma oncotic pressure can be d/t:
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14
Q

Albumin helps to regulate our plasma oncotic pressure. How can we decrease these levels => non-inflammatory edema?

A

Altering the amount MADE (cirrhosis or protein malnutrition) or increasing the amount loss (nephrotic syndrome)

    1. Liver diseases (cirrhosis): not enough proteins made
    1. Protein malnutrition: not enough intake of proteins -> not synth new albumin
    1. Kidney disease with nephrotic syndrome: too many proteins lost through filtration.
      *
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15
Q

What is the process that causes non-inflammatory edema if we have a decrease in plasma oncotic pressure?

A
  • 1. Proteins are lost
  • 2. Net movement of fluid into the tissue (interstitiam) from the blood
  • 3. Decrease renal perfusion => + RAAS system
  • 4. Attempts to hold onto Na+ and water, however, this cannot correct the deficit because we have a deficit of proteins
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16
Q

Describe how Na+ and water retention can cause non-inflammatory edema?

A

Causes BOTH: increase hydrostatic pressure and decreased osmotic pressure

  • Disease => Decrease renal perfusion => activation of RAAS system =>
  • Increased salt retention: increases volume of vascular system, which increase the hydrostatic pressure AND decrease in the plasma colloid pressure d/t dilution.
  • Activation of RAAS system is good at first to improve CO and restore normal perfusion. However, as the <3 worsens, Na+ and water retention => edema and effusion
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17
Q

Describe how lymphatic obstruction can cause non-inflammatory edema?

A
  • Trauma, fibrosis, invasive tumors, and microbes => lymphatic obstruction => lymphedema
    • Lymph system cannot to take up the fluid => LOCALIZED EDEMA called lymphedema
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18
Q

Lymphedema can be seen in what 2 conditions?

A
  • Filariasis (helminth infection/Wucheria): round worm infection that causes unilateral localized lymphedema.
    • Obstructive fibrosis => edema of the external genitalia and lower limbs that can be very extreme and called elephantiasis.
  • In the U.S, unilateral lymphedema is most commonly seen in breast cancer patients who have received axillary LN removal.
    • Causes severe edema of the area (arm) that the LN drained
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19
Q
    • What is the morphology of edema?
      • What do the organs look like?
A
  1. Subcutaneous edema
  2. Pulmonary edema
  3. Brain edema

Organs will look large and heavy

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20
Q

Describe subcutenaous edema.

A

Subcutaneous edema can be diffuse or it can occur in _areas with high hydrostatic pressur_e.

  • Hydrostatic pressure => influenced by gravity (thus, called dependent edema)
    • When standing => hydrostatic pressure is greatest in legs => edema in legs
    • When laying down => hydrostatic pressure is greatest in sacrum => edema in sacrum

Pressure over subcutaneous edema can leave a depression called pitting edema.

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21
Q

Subcutaneous edema raise what suspicions for the doctor from the patient?

A
  • 1. Cardiac disease
  • 2. Renal disease
    1. When significant, it can impair [wound healing and clearance of infection].
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22
Q

Describe how cardiac failure can cause edema.

A
  • Cardiac failure can cause pitting edema, pulmonary edema and pulmonary effusion
  • . In <3 failure, we see a decrease in pumping activity of the heart;
    • Congestion in the lungs d/t left ventricular failure -> congestion in pulmonary venous circulation -> backflow of blood-> pulmonary edema and pleural effusion
      • Fluid collects in the alveoli septa and around capillaries and impedes O2 diffusion. Edema fluid in alveolar spaces creates a favorable environment for bacterial infection.
      • In pulmonary edema, the lungs are 2-3X their normal weight and will give off a suctioned fluid that is frothy and a mixture or air, edema, and RBCs
      • Pulmonary effusion often accompany pulmonary edema and can compromise gas exchange by compressing pulmonary parenchyma.
    • Increases capillary hydrostatic pressure -> edema
    • Decrease in blood to kidneys -> + RAAS -> retention of Na+ and H20 -> increase in blood volume -> increases hydrostatic pressure and decreases oncotic pressure -> edema
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23
Q

Describe how renal failure can cause edema.

A

Renal failure can cause edema in two ways:

    1. Retention of Na+ and water -> increases in blood volume -> increase in intravascular hydrostatic pressure ->edema
    1. Nephrotic syndrome -> glomerulus are damaged, causing an excess of protein loss in the urine -> decreases oncotic pressure -> edema
  • Edema from renal failure initially appears in parts of the body that contains loose CT: like the eyelids (periobital edema) and is a characteristic sign.
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24
Q

Pt John comes in with begining renal failure. Where is the first place he will begin to see edema?

A

Renal failure => hypoproteinemia => parts of his body w/ loose CT, such as his eyes (periorbital edema).

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25
Q

What does brain edema cause?

A

LIFE THREATENING => will cause the brain to have narrowed sulci and distended gyri due to compression of the skull.

If severe, brain can herniate through foramen magnum or compress vasculature in brainstem

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26
Q
  • Peritoneal effusion (ascities) is most commonly due to ___________.
    • Any other causes?
  • What should we tell the patient that they are more prone to?
A

Ascites is most commonly d/t liver disease, which causes portal hypertension.

  • d/t decreased production of albumin.

Patients with acities will be at increased risk for: BACTERIAL INFECTIONS!

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27
Q

effusions involving the pleural cavity

A

Hydrothorax

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28
Q

effusions in the pericardial cavity

A

Hydropericardium

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29
Q
  • effusions in the peritoneal cavity.
A

Hydroperitoneum (ascites):

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30
Q
  • [Q:] What kind of fluid is escaping the intravascular compartment?
A
  1. Exudate: protein-rich and will look cloudy because it has blood cells. Inflammation will increase space between endothelial cells, cause vasodilation and stasis => forming exudate.
  2. Transudate: protein-poor, serous and water fluid caused by an increase in hydrostatic poressure (venous outflow struction) and decreased plasma oncotic pressure. An exception would by chylous effiusion, ascites caused by lymphatic blockage. It will be milky d/t presecend of lipids that are absorbed in the gut.
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31
Q

[Q:] Describe the events of liver failure.

A
  • Liver failure can result in edema and ascites.
    • Liver cell failure => decreased production of albumin in the liver -> ascites and edema
    • Portal HTN causes congestion -> ascites in the peritoneal cavity (abdomen)
      *
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32
Q
  • Hyperemia and congestion are a result of what?
A
  • Hyperemia and congestion are a result of increased blood volumes in tissues (local or systemic) => increase in hydrostatic pressure.
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33
Q

What is chronic passive congestion?

A

Chronic hypoxia (because venous blood is deoxygenated) causes congestion to become chronic => this causes

  • Capillaries to rupture and BCs begin to leak out and causes hemosiderosis.
  • After a while, this can result in i_schemic tissue injury and scarring._
    • Hemosiderosis: BCs leak out, get ingested by macrophages, creating hemosiderin-laden macrophages (aka heart-failure cells) on histo.
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34
Q

What cell will someone with chronic congestion have on histolofy?

A

You can see hemosiderin-laden macrophages;

BVs broke, BC leaked out and were ingested by macrophages, creating hemosiderin-laden macrophages (<3 failure cells)

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35
Q

What will congested tissue look like?

A
  • Tissue is blue (cyanotic) due to RBC stasis. (lack of O2)
  • Cappilares and veinsa re are engorged,
    • Extraversed RBCs in interstitial tissue
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36
Q
  • What is the difference between acute pulmonary congestion and chronic pulmonary congestion?
    *
A

Acute pulmonary congestion:

  • Alveolar capillaries are congested =>
  • Alveolar septal edema and focal intraalveolar hemorrhage

Chronic pulmonary congestion

  • CHF causes fibrotic septa, resulting in chronic pulmonary congestion and alveoli will have hemosiderin-laden macrophages.
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37
Q

What is the difference between acute hepatic congestion and chronic hepatic congestion?

A

Acute hepatic congestion:

  • Central vein and sinusoids are engorged with some death of central hepatocytes.

Chronic passive hepatic congestion

  • Chronic passive hepatic congestion is most often caused by right <3 failure => venous occulusion => obstruction of central vein (blood cant leave) => nutmeg liver (liver failure)
    • Nutmeg liver has a pattern of centrilobular necrosis: Centrilobular hepatocytes are red-brown d/t congestion (ischemic necrosis) since they are distal to the blood supply (receive less blood in the first place), compared to the surrounding, _tan hepatocyte_s (which may only undergo a fatty change)
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38
Q

What is hemostasis?

A

formation of a blood clot at an injury

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39
Q
  • If hemostasis (clot formation) damaged, can result in:
A
    1. Hemorrhagic disorder: Excessive bleeding where the normal hemostatic cannot stop bleeding
    1. Thrombotic disorders: blood clots (thrombi) form in blood vessels or in chambers in the heart
    1. Disseminated intravascular coagulation (DIC) => pathological activation of coagulation cascade when not necessary, which can lead to both the formation of thrombi problem and excessive bleeding (IV areas and mucosal surface) when we do need to clot since the excessive clotting is using up all of the clotting factors
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40
Q

What are the basic steps of hemostasis?

A
    1. Arteriole vasoconstriction d/t neural stimulation and endothelin released from endothelial cells.
    1. Primary hemostasis: formation of a weak platelet plug (adhesion => activation => aggregation).
    1. Secondary hemostasis: formation of a stabile platlet plug by depositing fibrin
    1. Stop hemostasis: stop forming the clot, resorption of clot and repair tissue.
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41
Q

Describe the process of primary hemostasis, formation of a weak platelet plug.

A

DAMAGE TO THE ENDOTHELIUM:

1. Transient vasoconstriction d.t neural impulses and endothelin released from endothelium

  1. Adhesion: Damage to the endothelium reveals a basement membrane filled with collagen and subcutaneous tissue filled with collagen.
  • Weibel Palade bodies in endothelial cells and alpha-granules of platelets fuse with the plasma membrane => uncoil => release vWF.
  • vWF binds to the exposed subendothelial collagen
  • GP1b on the platelets bind to the vWF on the collagen, initiating activation.
  1. Activation: Adhesion then causes activation, which is:
  • Change in shape:
    • _​P_latelets from flat -> spikey to increase SA,
    • Translocation of negatively charged phospholipids onto the surface of the platelets
  • Degranulation of alpha and dense granules with the release of ADP and TxA2).
    • Triggered by: thrombin, ADP, and TxA2
      • Thrombin activates other platelets by cleaving PAR (protein-activated receptor).
      • Activation and ADP promote recruitment (activation of more platelets)
        • ADP is released from dense granules => causes more activation and exposes GPIIb/IIIa receptors on platelets-> increasing affinity for fibrinogen /
        • Thromboxane A2 is made by platelet COX => promote aggregation.
    • Platelet activation and ADP promotes more platelets to be activated in a process called recruitment.
  1. Aggregation: Aggregation of platelets is promoted by ADP and TxA2 at the site of injury by linking GP2b/3a complexes from different platelets together using fibrinogen released from the plasma => forming a primary hemostatic plug.
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42
Q

Describe the process of secondary hemostasis, deposition of fibrin to form a stable, insoluble fibrin clot

A

​What happens: Coagulation cascade converts [prothrombin -> thrombin], which converts the [fibrinogen -> fibrin], stabilizing and making the clot insoluble.

  1. Originally, clotting factors (made by the liver) ARE INACTIVE
  2. Activation of the factors requires:
    1. Exposure to an activating substance
      1. Extrinsic pathway: tissue factor (TF) activates factor 7
      2. Intrinisic pathway: negatively charged surface on platelets activates factor 12.
    2. Presence of subendothelial collagen
    3. Ca2+
  3. End product: formation of insoluble fibrin clot
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43
Q

Describe the extrinsic and intrinsic pathway that occurs in secondary hemostasis.

A

Tissue factor is released when endothelial cells are damaged at the site of injury, activating the extrinsic pathwa.y

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44
Q

What is tissue factor?

A

A procoagulant glycoprotein that is formed on the surface of subendothelial cells whe injury occurs and activates the extrinsic pathway of the coagulation cascade.

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45
Q

How do we measure the extrinsic and intrinsic pathway and combined pathway.

A
  • Extrinsic pathway: prothrombin time (PT) assay assess the function of the proteins in the extrinsic pathway (factors 7)
    • Add tissue factor
    • Clotting should occur in 10-14 seconds.
  • Intrinsic pathway: partial thromboplastin time (aPTT) assess function of the proteins in the intrinsic pathway (factors 8, 9 and 11).
    • Not associating with: factor 7, prekallikrein, high molecular weight kininogen, lupus anticoagulants.
    • Add negative surface and Ca2+
    • Clotting should occur in 32-45 seconds
  • Combined abnormal APTT and PT: problem in the common pathway
    • Medical conditions: anticoagulants, disseminated intravascular coagulation (DIC), liver disease, vit. K deficiency, massive transfusion
    • Rarely dysfibrinogenemia; factor 5, 10 and 2.
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46
Q

Each step in secondary hemostasis involves what 3 things?

A
    1. Substrate: inactive factor
    1. Enzyme: activated factor
    1. Cofactor: reaction accelerator
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47
Q

Where does secondary hemostasis occur?

A

On the negative phospholipid surface of activated platelets.

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48
Q

[Q:] How do we stop clot formation/restrict it to the site of injury?

A
  1. Normal healthy endothelium covers tissue factor, which prevents coagulation
  2. Factors are only activated AT the site of injury d/t presence of neg. phospholipids
  3. Dilution with increased blood flow washes out activated clotting factors
  4. As fibrin covers up the platelet surface, no more coagulation can occur on the platelet
  5. Fibrinolysis dissolves clot after it heals via plasmin (endogenous fibrin dissolver)
    • {Plasminogen -> plasmin via tPA or factor XII–dependent pathway] => dissolves clot
      • a2-plasmin inhibitor inactivates plasmin
      • tPA comes 4rm endothelium and most active when bound to fibrin
    • As we break bown fibrin clots => increase number of D-dimers (breakdown products) => marker for thrombotic states
      *
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49
Q

What are the vitamin-K dependent factors and how are they activated?

A

2, 7, 9, 10, protein C and S.

  • Vitamin K dependent carboxylation must occur to bind Ca2+ => activate factors 2, 7, 9 and 10
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50
Q

What is coumadin?

A

Coumadin (warfarin) is a anticoagulant that blocks Vitamin K dependent decarboxylation => Ca2+ cannot bind to factors 2, 7, 9, 10, protein C and S => factors are not activated => coagulation does not occur.

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51
Q

What are the names of factors 1, 2 and 8?

A

1= fibrinogen/fibrin

2= prothrombin/thrombin

8= antihemophillic A factor (AHF)

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52
Q

What are hemorrhagic disorder?

A

Hemorrhagic disorders are disorders of the vessel walls, platlets or c_oagulatio factors_. They include primary hemostasis disorders, secondary hemostasis disorders that cause bleeding.

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53
Q

The clinical significance of hemorrhage depends on what?

A
  1. Volume of the bleed
  2. The rate at which it occurs
  3. Location of the bleed
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54
Q

Compare and contrast complications of acute, severe hemorrhage with chronic blood loss.

A
    1. Acute (rapid) loss of blood can have little effects on adults if small, however larger amounts can cause hypovolemic (hemorrhagic) shock.
    1. Bleeding in subcutaneous tissue may be inconsequential, but if it occurs in the brain (intracranial hemorrhage), it can cause death.
    1. Chronic EXTERNAL blood loss (d/t peptic ulcer or intracranial bleeding) => iron loss => anemia; however if the blood is not lost to the external environment => the iron is recovered and recycled and used to make Hb.
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55
Q

Primary hemostasis disorder are often due to what?

A

Abnormalities in the platelets: they can either be

  1. Quality of the platelets
  2. Number of platelets
    * Thrombocytopenia: decreased in the number of platelets
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56
Q

What clinical features are most common of primary hemostasis?

A
  1. Mucosal bleeding:
    1. Epistasis (nose bleeding)*
      1. most common
    2. GI bleeding
    3. Excessive mensutration (menorrhagia)
  2. Easy bruising and skin bleeding:
    1. Petachiae (< 3mm)
    2. Purpura (>3mm: larger)
    3. Ecchymoses (palpable)
  3. Excessive thrombocytopenia can cause intracranial bleeding
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57
Q

What are examples of disorders of HEREDITARY primary hemostasis?

What about ACQUIRED

A

Hereditary

  • 1. Von Willebrand disease
  • 2. Bernard Soulier syndrome
  • 3. Glanzmann thrombasthenia

Acquired: ASP inhibits COX (which makes TXA2) or renal failure.

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58
Q

What is a von Willebrand disease?

A

von Willebrand disease is a primary hemostatic adhesion disorder. It is the most common inherited coagulation disorder caused by a decrease number of vWF => problems with platelet adhesion => mild skin and mucosal bleeding.

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59
Q

What lab results will be see in a patient with vWF?

  • _____ Bleeding time
  • _____ PTT
  • ____ PT
  • ____ ristocetin test
A
  • Increased bleeding time
  • Increased PTT
    • Because vWF helps to stabilize factor 8.
    • If decreased vWF => decrease factor 8, however we show no symptoms of secondary hemostatic disorders.
  • Normal PT
  • Abnormal ristocetin test:
    • Ristocetin causes platelet aggluttination by causing [vWF to bind to G1Pb]. Lack of vWF => abnormal agluttination=> abnormal test
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60
Q

What is Bernard Soulier syndrome?

A

a primary hemostatic adhesion disorder caused by a lack of GP1b receptors on platelets, which impaired adhesion during primary hemostasis.

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61
Q

What is Glanzmann thrombasthenia?

A

Glanzmann thrombasthenia is a primary hemostatic aggregation disorder caused by a deficiency in GPIIb/IIIa complexes => impairs platelet aggregation.

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62
Q

Both Bernard Soulier syndrome and von Willebrand disease are adhesion disorders that cause a defect in primary hemostasis.

How do we differentiate them on peripheral smear?

A

Bernard Soulier syndrome (lack of GP1b receptor) will have GIANT platelets on a smear.

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2
3
4
5
Perfectly
63
Q

A patients who overdoses on aspirin (NSAIDs) will experience what problems?

A

NSAIDS => inactivate COX => decrease in thromboxane A2 => decrease in aggregation of platelets

64
Q

Disorders of secondary hemostasis are usually due to _________.

What are the clinical features?

A
  • Disorders of secondary hemostasis: are due to factor abnormalities that are heriditary or acquired => problems with coagulation
  • Clinical features:
    • Deep tissue bleeding into muscles and joints (hemiarthrosis)
    • Rebleeding after surgery
    • Intracranial bleeding can occur
65
Q

Secondary hemostasis disorders are caused by factor deficiencies/dysfunction that result in prolongation of _________.

A

PTT and/or PT

66
Q

What are acquired secondary hemostasis dirsorders?

Heriditary?

A

Acquired

  • 1. DIC
  • 2. Liver disease
  • 3. Vit K deficiency

Heriditary

  • Hemophilia A
67
Q

What is DIC?

What lab findings do we see? platelet count, PT/PTT, fibrinogen, other

A

DIC: patholothigic activation of the coagulation cascade that is almost always secondary to another disease. This causes

    1. Microthrombi in blood vessels, which will cause ischemia and infarction in tissues.
    1. Because we are using up our platelets, it will cause bleeding, especially from IV sites and mucosal surfaces.
  1. Decreased platlet count (bc making thrombi)
  2. Increase PT/PTT
  3. Decrease fibrinogen (bc making fibrin clots)
  4. Anemia
  5. _High D-dimer * BEST TEST FOR DIC_
68
Q

Vitamin K deficiency would cause what?

A

Impaired coagulation d/t decreased fx of factors 2, 7, 9, 10, protein C and S.

Vitamin K is _made by bacteria in the gu_t and activated in the liver. This, this is seen in:

  1. Newborns: lack bacteria in gut. Thus, at birth, vitK is given to child
  2. Long-term ABX: disrupts bacteria in gut
  3. Malabsorption: deficiency in fat-soluble vitamins.
69
Q

What is heparin?

A

Heparin is an anticoagulant that acts on the intrinsic pathway to prevent the formation of clots, but does NOT actively lyse them.

70
Q

What is heparin-induced thrombocytopenia?

How do we treat?

A

Heparin can cause thrombocytopenia (a decrease in the number of platelets).

  1. Unfractioned Heparin forms a complex with platelet factor 4 [HEP-PF4] => produces IgG.
  2. IgG will consume platelets by the spleen by recognizing [HEP-PF4]
  3. Fragments of the destroyed platelets will go into the cirulation and activate remaining platets = forming a blood clot (thrombus).
  4. Thisl, combined with damage endothelium => prothrombotic state.

Tx: Anti-coagulant that is not coumadin.

71
Q

Liver failure affects ________ hemostasis. How?

How do we measure affects?

A

Liver failure affects secondary hemostasis.

  • The liver makes our clotting factors (proteins) and activates vitamin K => decreased clotting factors and decrease vitamin K => less activation of factors.

Measure with: PT

72
Q

Describe Hemophila A.

A
73
Q

How can we differentiate disorders of fibrinolysis from DIC?

A

In both, we will see increased bleeding.

However, in disorders of fibrinolysis, fibrinolysis is occuring even though there is not clot to cleave. Thus, we will have excessive cleavage of serum fibrinogen, WITHOUT an increase in D-dimers.

74
Q

What is the difference between chronic passive liver congestion and portal hypertension?

A

Chronic passive liver congestion: Nutmeg liver that caused by central venous congestion d/t right heart failure* (or thrombosis). This will cause necrosis of liver cells.

  • Venous occlusion => portal vein congestion (decrease blood to liver) => liver disease.

Portal HTN: liver disease occurs first and then portal vein congestion 2nd.

75
Q

What is important for forming the primary platelet plug and are the surface where activated coagulation factors bind?

A

Platelets

76
Q

Injury and disorders of small vessels often present with

A

“palpable purpura” and ecchymoses, which can create a hematoma.

77
Q

Platetes are derived from ___________, which are located where?

A
  • Megakaryocytes are located in the bone marrow.
  • They send projections into blood vessels, where the platelets then bud off and flow away.
78
Q

How does our body know to convert fibrinogen?

A

Thrombin stimulates the conversion

79
Q

When plasmin is activated by tPA. What does it do?

A

Plasmin is a anti-coagulant (wants to prevent clots)

1. Cleaves fibrin and serum fibrinogen to prevent future clots

2. Destroys coagulation factors

3. Blocks platelet aggregation

80
Q

When is tPA most active?

A

tPA (tissue plasmin- activator) most active when bound to fibrin.

  • This characteristic makes t-PA a useful therapeutic agent, since its fibrinolytic activity is largely confined to sites of recent thrombosis.
81
Q

What regulates plasmin?

A

tPA;

Once activated, plasmin is in turn tightly controlled by counterregulatory factors such as α 2 -plasmin inhibitor, a plasma protein that binds => inhibts free plasmin [decrease in the breakdown of clots]

82
Q

10.List and discuss the activities of thrombin.

A
    1. Converts fibrinogen => cross-linked fibrin
    1. Amplifies coagulation process, by activating factor 11 and cofactors 5 and 8.
    1. Stabilizes secondary hemostatic plug by activating factor 13 (fibrin-stabilizing factor)
    1. Activates platelets via protease-activated receptors (PARS)
    1. Pro-inflammatory effects: PARS are also expressed on inflammatory cells, endothelium and other cells types.
      * Activation by thrombin mediates pro-inflammatory effects => helps with tissue repair and angiogenesis.
    1. Antithrombotic functions:
      * When thrombin encounters normal endothelium: changes from a procoagulant => anticoagulant. This prevents clotting in other places besides site of injury.
83
Q

Thrombin has what 2 kinds of effects: describe them.

A

Pro-inflammatory effects and antithrombotic functions:

  • Pro-inflammatory effects: PARS are also expressed on inflammatory cells, endothelium and other cells types.
    • Activation by thrombin mediates pro-inflammatory effects => helps with tissue repair and angiogenesis.
  • Antithrombotic functions:
    • When thrombin encounters normal endothelium: changes from a procoagulant => anticoagulant. This prevents clotting in other places besides site of injury.
84
Q

a. Types and functions of cytoplasmic granules in platelets

A
  • α-Granules have the adhesion molecule P-selectin on their membranes ( Chapter 3 ) and contain proteins involved in coagulation, such as fibrinogen, coagulation factor V, and vWF, as well as p_rotein factors that may be involved in wound healing_, such as fibronectin, platelet factor 4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-B)
  • Dense (or δ) granules contain adenosine diphosphate (ADP) and adenosine triphosphate, ionized Ca2+, serotonin, and epinephrine.
85
Q

What do Protein C and S do?

Low protein C and S will do what?

A

They are anti-coagulants, inactivating factor 5a and 8a

  • Deficiency will cause increased risk of venous thrombosis.
86
Q

Describe the action of the following

  1. PGI2
  2. NO
  3. ADP
  4. Heparin-like molecules
  5. tPA
  6. Thrombomodulin
A
  1. PGI2 prevents platelet aggregation (opposite of thromboxane A2)
  2. NO causes vasodilation
  3. Heparin-like molelcules bind to anti-thrombin III (ATIII), which inactivate thrombin and coagulation factors (9a, 10a, 11a, 12a)
  4. tPA activates fibrinolysis.
  5. Thrombomodulin: causes thrombin to activate protein C (which requires vitamin K and protein S) => inactivates factor 5 and 8 => turns off coagulation
87
Q

12.Describe the potential antithrombotic influence of the endothelium, and specifically describe the mechanisms by which the endothelium exerts this influence.

A

Typically, the endothelium is anti-thrombotic (preventing random thrombosis) by:

    1. Blocking exposure to subendothelial collagen and tissue factor (TF)
    1. Produced PGI2, NO and ADPase (prevent activation of platelets) , which causes vasodilation and inhibits aggregation of platelets
    1. Secretes heparin-like molecules, which bind to anti-thrombin III (ATIII), which inactivate thrombin and coagulation factors (factor 9a, 10a, 11a and 12)
    1. Secretes tPA, which converts activate fibrinolysis: [plasminogen -> plasmin], which will then cleave fibrin, serum fibrinogen, coagulation factors and blocks platelet aggregation
    1. Secretes thrombomodulin, which redirects thrombin to activate Protein C, which inactivates factor 5 and 8 => turns off coagulation.
88
Q

What is a thrombus** and a **embolus?

Where do they occur and most common location?

A

Thrombus: pathological formation of an intravascular blood clot at a particular site in a artery or a vein.

  • The most common location is in the deep veins (DVT) of the leg, below the knee

Embolus: a traveling occlusion (solid, liquid or gas) that causes blockage where it lands and its s_ymptoms depend on where it lands._

89
Q

How do we know if the clot is what killed the patient?

What do antemortum and post-mortum look like?

A

We need to determine if the clot occurred before death or after death.

  • If the clot occured before death (antemortum), it will have [lines of zahn: alternating layers of pale areas (platelet/fibrin) and red areas (RBCs)] and be [attached to the wall of the vessel].
    • Thus, is the COD of the patient.
  • Post-mortum (pooled blood) clots are
    • JELLatinous (think of grape jelly),
    • have a dark red portion depending on where the RBC pooled by gravity
    • yellow “chicken fat” portion.
    • do NOT attach to BV.
90
Q

Virchows triad are the MAIN abnormalities that cause thrombosis. What are they?

A
  1. Endothelial injury
  2. Stasis or turbulent blood flow, which can cause damage to the endothelium
  3. Hypercoagubility
91
Q

How does damage to the endothelium lead to the formation of a thrombus?

A

Direct injury, infection, inflammatory mediators, hypercholesterol, smoking and turbulent BF => damage endothelium.

  • Damage to endothelium causes it to go from being [anti-thrombotic -> pro-thrombotic]:
    • _decrease in NO a_ctivity => activate the endothelium => increase adhesion molecules => downregulate thrombomodulin => downregulate activated protein C => coagulation => thrombus
  • Secretes plasminogen activator inhibitors (PAIs) => down regulates tPA => limit fibrinolysis
92
Q

How do alterations in normal blood flow lead to thombosis?

A
  • Normally, blood flow is continuous and laminar, keeping platelets inactivated and dispersed.
  • Turbulence can cause arterial and cardiac thrombosis by damaging endothelium, as well as by forming countercurrents that contribute to local pockets of stasis.
  • Stasis is a major cause of venous thrombi.
  • They both increase risk for thrombosis by:
  1. Activating the endothelium, which causes procoagulation and leukocyte adhesion.
  2. Bringing platelets into contact with endothelium
  3. Prevent washout and dilution of clotting factors.
  4. Prevents influx of clotting inhibiting factors
93
Q
  • When would alteration in normal blood flow occur?
A
    1. At bifurcations.
      * Bifurcations are more prone to damage d/t atherosclerotic plaque formation => causes even more turbulence
    1. Ulcerated atherosclerotic plaques not only expose subendothelial vWF and tissue factor but also cause turbulence.
    1. Dilated vessels (aneurysms and hemorrhoids) => stasis
    1. Int_ernal obstruction_
    1. External interference/compression
      * <3 attack can compress coronary arteries
  • 6. Inadequate heart chamber fuction
    • A-fib can cause stasis
94
Q

What is hypercoagubility?

A
  • also called thombophilia
  • Any disease of the coagulation cascade that makes it more likely for thrombosis to occur.
95
Q

What is the classic presentation of a hypercoaguble state?

A

Recurrent DVT or DVT at a a young age.

96
Q

What are primary hypercoagubility diseases?

A

Primary hypercoagubility diseases are GENETIC and increase risk for thrombosis.

  • 1. Factor V Leidin
  • 2. Prothrombin gene mutation (prothrombin G20210A mutation)
  • 3. Protein C and S deficiencies
  • 4. Antithrombin III deficiency
97
Q

What are secondary hypercoagibility diseases?

A

Secondary hypercoagibility diseases are ACQUIRED and increased risk for thrombosis.

  1. Heparin-induced thrombocytopenia
  2. Antiphospholipid syndrome
  3. Oral contraceptive use
  4. DIC
  5. Prolonged bed rest or immbolization.
98
Q

Factor V Leiden mutation

A
  • Factor V Leidin mutation is THE MOST COMMON GENETIC HYPERCOAGUOPATHY:
  • common in ppl with DVTs, particulary Caucasions.
  • Mutation: Arg => Glu substitution in AA 506 causes factor 5 to be resistant to cleavage by protein C => thrombosis.
99
Q

How can we test Factor V Leidin mutation?

A
    1. Genetic testing
  • 2. APC (activated protein C) restistance testing: measure the clotting time before and after APC is added to blood sameple that is clotted with snake venom.
  • Those + are resistant to APC and clotting time plateaus.
100
Q

Prothrombin gene mutation (prothrombin G20210A mutation)

A
  • Single nucleotide change (G20210A) in the 3’-untranslated region that leads to HIGH prothrombin levels => increase thrombin => increased risk of venous thrombosis.
101
Q

Deficiencies in protein C and S lead to what?

What do they do normally?

A
  • Deficiency in protein C and S decrease negative feedback on the coagulation cascade. Normally, they inactivate factor 5 and 8.
  • Decrease in protein C and S => high factor 5 and 8 and i_ncreases risk for warfarin-skin necrosis_ => hypercoagulation.
102
Q

What is heparin induced thrombocytopenia?

A

Heparin can cause thrombocytopenia (a decrease in the number of platelets), creating a pro-thrombotic state when combined with endothelial damage.

  1. Unfractionated heparin forms a complex with platelet factor 4 [HEP-PF4] => produces IgG.
  2. IgG crosslinks [Fc receptor on the platelet and the HEP-PF4 complex]
  3. Causes increased production of platelet factor 4, platlet activation and aggregation => thrombosis => decreasing number of platelets
  4. => prothrombotic state when combined with damage to endothelium

Tx: Anti-coagulant that is not coumadin.

103
Q

What is warfarin skin necrosis?

A

Patients with deficiencies in protein C and S have an increase risk for warfarin skin necrosis.

  • Coumadin blocks expoxide reductase in the liver => cant activate Vit K => decreases activation of factors 2, 7, 9, 10, protein C and S.
  • Thus, if we give a patient with low protein C and S coumadin (without another anti-coagulant)
    1. ​​Decreased production of new 2, 7, 9, 10, C and S.
    2. Old factors willl then start to decrease: Protein C and S are the first to degrade because they have the shortest 1/2 life.
    3. Thus, depletion of anti-coagulants occurs 1st because we are already low on C and S.
    4. When anti-coagulants (C and S) are gone, pro-coagulants (2, 7, 9 and 10) are present without an anti-coagulant => increases risk for activation
    5. Increase activation of pro-coagulants => increases risk for formation of a thrombus (hypercoaguble state), especially in the skin.

​THUS; patients on coumadin are also given heparin to prevent clot formation until 2, 7, 9 and 10 are destroyed.

104
Q

What is antiphospholipid antibody syndrome?

A
  • An autoimmune disease where patients produce of antiphospholipid antibodies, which attack phospholipids in cell membrane and proteins bound to the phospholipids (damage membrane) to produce a hypercoagulable state (thrombotic). There are 2 forms:
    • Primary: antiphosholipid AB syndrome occurs alone, without any other autoimmune disease
    • Secondary: occurs with another autoimmune disease, especially lupus.
105
Q

What are the clinical manifestations of antiphospholipid AB syndrome?

A

Hypercoagulable state, which can cause recurrent arterial/venous thrombosis and miscarriages or stillbirth.

  • Arterial thrombosis can cause <3 attack, stroke or limb ischemia (bc decrease in O2 delivary)
    • Mitral valve vegetations
  • Venous thrombosis can cause DVT.
    • Part of a DVT can break off and cause an embolism in the lungs (pulmonary embolism) or _kidneys (_causing renovascular HTN, renal microangiopathy => renal failure)
  • Miscarriages because patient will have problems wiht growth and differentiation of trophoblasts, causing there to be no placenta
106
Q
  • Arterial/cardiac thrombi typically occur at sites of ____________________
  • Venous thombi occur at sites of __________.
A
  • Arterial/cardiac thrombi typically occur at sites of turbulence of damage to endothelium
  • Venous thombi occur at sites of stasis.
107
Q

How do thrombi propagate in the blood?

A

Thrombi are attached to the vascular surface where the injury occured.

  • Arterial thrombi will move retrograde
  • Venous thrombi will move in the direction of blood flow

​BOTH TO THE <3.

The part that propagates is the part that is most likely to break off and embolize.

108
Q

What is the difference between arterial and venous thrombi?

Are they occlusive?

Arterial: common places, what do they consist of, major causes and more prone to embolize what areas?

Venous: common places, what do they consist of, features of the clot

A
  • Arterial thrombi are frequently occulusive.
    • Most common places (in order): coronary (MI), cerebral (stroke) or femoral artery.
    • Consist of: fibrin, platelets, RBC and leukocytes.
    • Major causes include: atherosclerosis, MI, rheumatic heart disease,
    • More prone to embolize: brain, kidneys and spleen because they have a RICH BS.
  • Venous thrombi are always occulsive.
    • Most common in: slow venous circulation of the LE
    • Consist of: red cells and few platelets,making them known as red/ stasis thrombi.
    • Features: firm, attached to vessel wall and contain lines of Zahn.
109
Q

Venous thrombi are also called what?

A

Phlethrombosis.

110
Q

What is the difference between superficial venous thrombi and deep venous thrombi (DVT)?

A
  • Superficial venous thrombi most often occur in saphenous vein and can cause [_congestion, swelling, pain and tendernes_s] BUT RARELY embolize.
  • DVT occur in large veins of the leg at or above the knee and cause unilateral swelling, pain, warmth and redness below the knee. Dont always occur b/c collateral channels can open
    • More serious because they CAN EMBOLIZE.
      *
111
Q

What are risk factors for DVT?

A
  • 1. Genetics
  • 2. Inactivity/immnobility
  • 3. Injury: cause pro-coagulant release, liver makes clotting factors and decrease tPA production.
  • 4. Hormone replacement or oral contraceptives
  • 5. Smoking
  • 6. Pregnancy
  • 7. Cancer (Trousseau syndrome)
  • 8. Obesity
  • 9. Age
112
Q
  1. Infected endocardial thrombi/vegetation
  2. Nonbacterial thrombotic endocarditis
  3. Libman-Sacks endocarditis
A

Vegetations are a mixture of immune cells and blood clots on heart valves.

  1. Infective endocardial vegetations: bacteria or fungi can attach to heart valves, causing damage to endothelium and distrubed blood flow => form infective thrombotic masses
  2. Nonbacterial thrombotic endocarditis: uninfected vegetations that develop on uninfected valves in a person in a hypercoagulable state
  3. Libman-Sacks endocarditis: sterile errucous(non-bacterial) endocarditis that occurs with lupus
113
Q

What are the 4 fates of the thrombus?

A

1. Propogate (grow) by adding more platelets and fibrin

2. Embolize

3. Go away d/t spontaneous fibrinolysis

4. Organize and recanalize

114
Q

Are newer or older thrombus more likely to go away by spontenous fibrinolysis?

A

Newer. Older thrombus are more resistant to lysis.

115
Q

What can be given to a patient to treat to dissolute a thrombus that causes a embolic stroke?

A

Give exogenous tPA within 6 hours of onset.

116
Q

What happens when a thrombus undergoes organization and recanilzation?

A
  • Older thrombi undergo organization by growing endothelial cells, _smooth cell_s, and fibroblasts to create channels that will allow capillaries to grow and recover lost BF.
  • Recanilization can convert thrombus => smaller mass of CT that incorperates into the wall of the BV, producing a scar
    *
117
Q
A
118
Q

Q:] What happens if a thrombus dislodges?

A

Becomes an embolus that goes to the lungs (pulmonary embolism).

Originates from a LE DVT and lodges in pulmonary arterial circulation

119
Q

Embolism is a detached intravascular solid, liquid or gas carried by the blood from its original point of origin => distant site, where it enounters vessesl too small for it to travel through.

What does it cause?

Most embolisms are what?

A
  • Partial or complete vessel occulusion, depending on size and location of embolism.
  • Most are dislodged thrombi (thromboemolisms)
120
Q

Pulmonary embolism (PE): PE originate from fragments of DVT -> larger veins and _____ side of heart -> lodged within pulmonary _____ circulation

A

RIGHT SIDE OF THE HEART

PULMONARY ARTERIAL CIRCULATION

121
Q

_____________ is THE most common thromboembolic disease..

A

Pulmonary embolism

122
Q

The clinical outcome is dependent on the size of the PE.

Describe the sizes and outcomes.

A
  • Large PE (saddle embolus) lodges in primary arterial trunk at the pulmonary artery bifurcation usually instanteously kill you
  • If medium:
    • Travel more peripherally and patients may have SOB.
    • Can cause pulmonary hemorrhage, but does not cause infarction bc the lung is has 2 BS ( pulmonary arteries and bronchial arteries). Bronchial as r enough to prevent infarction
  • Extremely small emboli emboli can be asymptomic.
123
Q

What pattern do we see in ppl with PE?

A
  • Most (60-80%) PEs are small and overtime will incorperate into the vessel wall and leave behind a scar.
  • Thus, most are clinically silent because they’re small and lung has 2 BS.
  • A pt with 1 PE has an increased risk for more.
124
Q
  • When emboli obstruct more than 60% of the pulmonary circulation: what happens?
A

can cause sudden death, right heart failure, or /;

125
Q

What are the 5 types of embolisms?

A

1. Thromboemboli (pulmonary or systemic thromboembolisms)

2. Fat/marrow emboli

3. Air emboli

4. Septic emboli

5. Amniotic fluid emboli

126
Q

What are systemic thromboemboli?

A

Systemic emboli arise from the left heart and lodge into the arterial circulation, depending on the source and amount of blood flow.

  • (80%) arise from intracardiac mural thrombi, 2/3 of which are associated with left ventricular wall infarcts and another 1/4 with left atrial dilation and fibrillation.
127
Q

Systemic thromboemboli are likely to lodge where

A

In contrast to venous thromboemboli, they can lodge in many places besides the lung.

In order: LE (75%), brain, intestines, kidneys, spleen, and UE

128
Q

What is a fat/marrow embolism?

A
  • Fat emboli are emboli of the bone marrow (which contains fat)
  • Cause: Occur in 90% of skeletal muscle injurie_s (fractures o_f long bones or soft tissue trauma), often when doing chest compression => introduce bone marrow into circulation => fat embolism.
    • thus, they are commonly seen post-mortum
129
Q

What is fat embolism syndrome?

A
  • Fat embolism syndrome causes respiratory distress, mental status changes (irritability, delirium, coma), anemia and thrombocytopenia.
    • Fatal in about 10% of people
130
Q

What is an air embolism?

A

The introduction of air (iatrogenic) that forms gas bubbles in the circulation, often due to cardiac catheterization.

Theu coalesce and form masses that block blood flow and cause distal ischemic injury.

131
Q

In what cases can we see a gas embolus?

A

Decompression sickness:

    1. As patient dives, partial pressure increases, forcing nitrogen to dissolve in the blood.
    1. As the diver comes up rapidly, nitrogen does not have enough time to leave the blood and will precipitate out of the blood as small gas bubbles and go into tissue.

Causes: joint and muscle pain (bends) and respiratory symptoms (chokes)

132
Q

What is the chronic form of decompression sickness called?

A

Caisson disease.

  • Happens to pppl that worked in pressurized vehicles while working on bridges.
  • Persistent bubbles in the skeletal system leads to multifocal ischemic necrosis of the bone (femoral head, tibia and humerus).
133
Q

Amniotic fluid embolism

A

Amnoitic fluid into maternal pulmonary circulation during labor or delivery, causing an anaphayltic-allergic reaction in mom.

5th most common cause of maternal mortality, often resulting in neurological deficits in those that survive.

Mom will have: SOB (dyspnea), cyanosis, and shock, followed by n_eurological symptom_s. If the pt survives, mom can get DIC -> kill her.

134
Q

What will we find on autopsy in someone who died from amniotic fluid embolism?

A
  • Squamous cells from kin, hair, fat, mucin from the baby in the moms BV
135
Q

What are septic emboli?

and clinical manifestations.

A

Blood-borne infective emboli that may occur in endocarditis when vegations on the valve break off and lodge in other wides.

Manifestations:

  1. Skin microemboli called Janeway lesions (purpuric)
  2. Retinal microemboli called Roth spots
  3. Vascular damage to nails called splinter hemorrhages.
136
Q

What is an infarct?

A

An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage.

137
Q

Contributing mechanisms to infarction

A

Vast majority are d/t

  1. arterial thrombosis
  2. arterial embolism.
138
Q

What factors influence infarcts?

A

1. Anatomy of vascular supply* most important

2. Rate of occlusion

3. Vulnerability of tissue to hypoxia

139
Q

How can we classify the morphology of infarcts?

A

By color and the prescence or absence of infection:

1. Red (hemorrhagic) infarcts

2. White (anemic) infarcts

140
Q

What are red (hemorrhagic) infarcts?

A

Red (hemorrhagic) infarcts are rich in RBC and most commonly occur in LE.

Occur in:

  1. Venous occlusions, which causes stasis of blood.
  2. Loose tissues like lungs
  3. Tissues with 2 BS (lungs and SI)
  4. Sites that were previously occluded and necrototized when flow is reestablished.
141
Q

What are white (anemic) infarcts?

A

White (anemic) infarcts are platelet rich and caused by arterial occlusions in compact (solid) tissue that have one BS d/t high shear stress.

  1. solid organs that have 1 BS: [heart, spleen and kidneys]
  2. arthersclerosis of the coronary and cerebral arteries ******
142
Q

Organs more dependent on one vessel-> ____ infarction

Organs with 2 BS -> ____ infarction

A
  • Organs more dependent on one vessel-> white infarction
  • Organs with 2 BS -> red infarction
143
Q
  • Factors that influence the development of an infarct: Rate of occlusion
A
  • Slower occlusions are more likely not going to cause tissue damage since collateral supply will have time to adequately compensate for the occlusion.
144
Q
  • Factors that influence the development of an infarct: Tissue vulnerability to hypoxia
A
  • Neurons die to hypoxia in 3-4 min.
  • Myocardial cells die to hypoxia die in 20-30 min.
  • Fibroblasts within the myocardium take several hours to die of hypoxia
  • Never see liver infarcts

Thus, brain is most vulnerable

145
Q

All infarcts tend to be ______-shaped: _______.

A

wedge shaped: the occluded vessel is at the apex and organ periphery is the base.

146
Q

What is the dominant histologic feature of infarction?

What is the exception?

A
  • Display ischemic coagulative necrosis unless the person died before the histology took place (it takes 4-12 hours).
    • Followed by inflammation along margins that lasts hours -> days
    • THEN, folowed by reparative response (days to weeks) initiated in the preserved region to form a scar.
  • Exception: brain undergoes liquifactive necrosis.
147
Q

What is shock?

A
  • Shock: systemic hypoperfusion and cellular hypoxia d/t from reduction in CO or hypotension
    • Injury is only reversiblr at the begining.
148
Q

What are the 3 types of shock?

A
  1. Cardiogenic shock
  2. Hypovolemic shock
  3. Septic shock (shock associated with systemic inflammation)
149
Q

How does cardiogenic shock occur and what causes it?

A
  • Mechanism: Obstruction of flow or failure of myocardial pump d/t intrinsic myocardial damage, extrensic compression => decrease in CO.
  • Causes: MI, ventricular rupture, ventricular arrhythmias, cardiac tamponade, PE
150
Q

How does hypovolemic shock occur and what causes it?

A
  • Mechanism: Low blood volume causes low CO.
  • Causes: massive hemorrhage or fluid loss from severe burns, trauma, V/D.
    *
151
Q

How does septic shock occur and what causes it?

A

Septic shock is d/t microbial infection/superantigens/burn/trauma/pancreatitis that causes systemic inflammation =>

  • release of innate/adaptive inflammatory mediators => vasodilation and venous blood pooling.
  • => can lead to:
    • tissue hypoperfusion,
    • decrease O2 in tissue
    • metabolic derangements
  • => organ dysf/failure/death
152
Q
  • Septic shock is most commonly triggered by (decreasing order): ______, _______ and ______
A
  1. gram + bacteria
  2. gram - bacteria
  3. fungi
153
Q
  • Pathogenesis of Septic Shock: How do we get from pathogens to decreases tissue oxygenation?
    • Describe the steps.
A
    1. Inflammatory responses
      * A. PAMPS on pathogenic bacteria and fungi interact with TLRs of the innate immune system.
      * B. Once activated innate immune system releases TNF, IL-1, IFN-γ, IL-12, IL-18, and HMGB1.
      • Release ROS, lipid mediators, prostaglandins, and PAF.
        * C. Complement system is also activated directly and through proteolytic activity of plasmin => C3a/C5a, C3b=> pro-inflammatory state.
        * D. Hyperinflammatory state cause IL-10 and sTNF release and apoptosis => cause immunosupresion, which is counter-regulatory.
      • Thus, septic patients may switch between hyperinflammatory and immunosuppressed states.
    1. Endothelial activation
      * A. Inflamm cytokines loosen endothelial tight jcts => increase permeability
      • => Leads to vasc leakage of protein- rich edema, causing hypovolemia
        * B. Endothelium releases NO => Vasodilation => decreased bp => hypotension
    1. Procoagulation
      * Increase factor 12 and TF and decreased antithrombin and protein C => decrease fibrinolysis (by increasing plasminogen activator inhibitor-1) => tissue begins to thrombose.
      * This can cause DIC
    1. Metabolic abnormalities such as insulin resistance and hyperglycemia occur
  • 5. Hypotension, hypovolemia and thrombosis alllll cause a DECREASE in ORGAN OXYGENATION => end-stage multiorgan failure
    *
154
Q

What exactly causes the end-stage multi-organ dysfunction?

A
  • Systemic hypotension, lots of edema, and small vessel thrombosis: decrease delivery of O2 and perfusion of tissues.
  • Cytokines and secondary mediators=> decrease contraction of heart => reduce CO.

Lead to mutilple organ failure (usually kidneys, liver and lungs) => death.

155
Q

25.Describe the clinical consequences/prognosis of shock.

A

The prognosis varies with the origin of shock and its duration

  • Hypovolemic shock and cardiogenic:
      1. Hypotension
      1. weak rapid pulse
      1. tachypnea
      1. cool, clammy, cyanotic skin.
  • Septic shock:
      1. Skin may initially be warm and flushed d/t vasodilation.
      1. Then, shock causes cardiac, cerebral and pulmonary dysftion => disturb electrolytes and metabolic acidosis
    • Second phase: renal insufficieny => decrease urine output
156
Q

What cell and tissue changes do we see in those with cardiogenic or hypovolemic shock?

A

Changes caused by hypoxia: seen mostly in the brain, heart, lungs, kidneys, adrenals and GI tract.

  • Adrenal: inactive cells become active and use up lipid stores by converting them to steroids
  • Kidenys: acute tubular necrosis.
  • Lungs: sepsis can cause diffuse alveolar dmage (shock lung)
  • Microthrombi in organs listed above.
  • Serosal surface and skin: petechail hemorrhages.

All of these changes, except to ones in brain and heart can go back to normal if the patient survives.

MOD 1: DR (11 decks)

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