Kumar Et Al Chapter 4 Review

Front 1

What percentage of lean body weight is water?

Back 1

- 65%
(Two thirds of the body's water is intracellular, and the remainder is in extracellular compartments, 5% of total body water is in blood plasma)

Front 2

What changes in capillary pressure (1) and colloid osmotic pressure (2) can result in increased interstitial fluid?

Back 2

- (1) Increased capillary pressure
- (2) diminished colloid osmotic pressure

Front 3

What is the meaning of Anasarca ?

Back 3

- Severe and generalised oedema with widespread subcutaneous tissue swelling

Front 4

What are the five pathophysiologic categories of oedema?

Back 4

- Increased hydrostatic pressure
(focal impairment in venous return and congestive heart failure)
- Reduced plasma osmotic pressure
(occurs when albumin, the major plasma protein, is not synthesized in adequate amounts or is lost from the circulation; nephrotic syndrome glomerular capillaries become leaky, Reduced albumin synthesis occurs in the setting of severe liver diseases or protein malnutrition)
- Lymphatic obstruction
( results in lymphedema via chronic inflammation with fibrosis, invasive malignant tumors, physical disruption, radiation damage, and certain infectious agents)
- Sodium retention
(Salt retention occurs whenever renal function is compromised. antidiuretic hormone (ADH) from the posterior pituitary)
- Inflammation

Front 5

Hyperemia is an active process in which?

Back 5

- Arteriolar dilation
- Leads to increased blood flow

Front 6

Microscopically, acute pulmonary congestion exhibits engorged alveolar capillaries often with ?

Back 6

- Alveolar septal oedema
- Focal intra-alveolar hemorrhage

Front 7

In chronic pulmonary congestion the septa are?

Back 7

- Thickened and fibrotic
- The alveoli often contain numerous hemosiderin-laden macrophages
(heart failure cells)

Front 8

In acute hepatic congestion, the central vein and sinusoids are distended; centrilobular hepatocytes can be frankly ischemic while the periportal hepatocytes—better oxygenated because of proximity to hepatic arterioles—may only develop ?

Back 8

- Fatty change

Front 9

In chronic passive hepatic congestion the centrilobular regions are grossly red-brown and slightly depressed (because of cell death) and are accentuated against the surrounding zones of uncongested tan liver is called?

Back 9

- Nutmeg liver
(Microscopically, there is centrilobular haemorrhage, haemosiderin-laden macrophages, and degeneration of hepatocytes)

Front 10

Which distal end of the blood supply to the liver, it is prone to undergo necrosis whenever the blood supply is compromised ?

Back 10

- Centrilobular area

Front 11

Tissue hemorrhage can occur in distinct patterns discuss them below;
(1) haematoma
(2) petechiae
(3) purpura
(4) ecchymoses
(5) haemothorax, haemopericardium, haemoperitoneum, or haemarthrosis

Back 11

- (1) Haemorrhage may be external or contained within a tissue
- (2) Minute 1- to 2-mm hemorrhages into skin, mucous membranes, or serosal surfaces
- (3) (≥3 mm) haemorrhages
- (4) (>1 to 2 cm) subcutaneous haematomas
- (5) a large accumulation of blood in a body cavity

Front 12

What is the name of a potent endothelium-derived vasoconstrictor, that induces brief period of arteriolar vasoconstriction post injury?

Back 12

- Endothelin
(augments a reflex neurogenic mechanisms)

Front 13

An injured endothelial exposes?, which facilitating platelet adherence and activation.

Back 13

- Subendothelial extracellular matrix (ECM)

Front 14

Upon exposure of the subendothelial extracellular matrix cause platelet to go through conformational change which increases surface area and results in release of secretory granules. Within minutes the secreted products recruit additional platelets (aggregation) to form a haemostatic plug; this process is referred to?

Back 14

- Primary haemostasis

Front 15

Secondary haemostasis involves the culminating of thrombin and then thrombin cleaves circulating fibrinogen into insoluble fibrin, creating a fibrin meshwork. Which tissues factors act in conjunction with factor VII as the major in vivo initiator of the coagulation cascade?

Back 15

- Factor III
- Thromboplastin
(tissue factor is a membrane-bound procoagulant glycoprotein synthesized by endothelial cells)

Front 16

Polymerised fibrin and platelet aggregates form a solid, permanent plug to prevent any further haemorrhage. Name one of the counter-regulatory mechanisms of clot formation?

Back 16

- Tissue plasminogen activator
(t-PA)

Front 17

What is produced by the endothelial cells impede platelet adhesion? Endothelial cells also elaborate adenosine diphosphatase, which degrades adenosine diphosphate (ADP) and further inhibits platelet aggregation

Back 17

- Prostacyclin (PGI2)
- Nitric oxide
(potent vasodilators and inhibitors of platelet aggregation; their synthesis by the endothelium is stimulated by several factors produced during coagulation (e.g., thrombin and cytokines)

Front 18

The endothelial mediates anticoagulant effects how?

Back 18

- Membrane-associated heparin-like molecules
(Enhance the inactivation of thrombin and factors 5,8 and 11 by the plasma protein antithrombin III )
- Thrombomodulin
(binds to thrombin and converts it from a procoagulant into an anticoagulant via its ability to activate protein C, which inhibits clotting by inactivating factors Va and VIIIa)
- Tissue factor pathway inhibitor
( directly inhibits tissue factor–factor VIIa and factor Xa activities)
- Protein S
(co-factor for protein C, which inhibits tissue factor–factor VIIa and factor Xa activities)

Front 19

Endothelial cells syntheses what protease that cleaves plasminogen to form plasmin; plasmin, in turn, cleaves fibrin to degrade thrombi?

Back 19

- Tissue-type plasminogen activator (t-PA)

Front 20

trauma and inflammation of endothelial cells induce a prothrombotic state that alters the activities of platelets (1), coagulation proteins (2), and the fibrinolytic system (3), discuss each system?

Back 20

- (1) Platelets
(platelets contact the underlying extracellular matrix; subsequent adhesion occurs through interactions with von Willebrand factor which is released by epithelium and in serum)
- (2) Procoagulant effects
( tumor necrosis factor [TNF] or interleukin-1 [IL-1]) or bacterial endotoxin, endothelial cells synthesize tissue factor, the major activator of the extrinsic clotting cascade)
- (3) Antifibrinolytic effects
(Endothelial cells secrete inhibitors of plasminogen activator (PAIs), which limit fibrinolysis and tend to favor thrombosis)

Front 21

Platelets are disc-shaped, anucleate cell fragments that are shed from what cell in the bone marrow into the blood stream?

Back 21

- Megakaryocytes

Front 22

Their function depends on several glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules, what are they and what is contained in them?

Back 22

- α-Granules
(have the adhesion molecule P-selectin on their membranes and contain fibrinogen, fibronectin, factors V and VIII, platelet factor 4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β)
- Dense (or δ) granules contain ADP and ATP, ionized calcium, histamine, serotonin, and epinephrine

Front 23

What three process occurs after platelets encounter ECM constituents such as collagen and the adhesive glycoprotein vWF?

Back 23

- Adhesion and shape change
(GpIb is a receptor bound on platelet and which binds to vWF to ensure adherence )
- Secretion
(calcium is required in the coagulation cascade, and ADP is a potent activator of platelet aggregation. ADP also begets additional ADP release, amplifying the aggregation process)
- Aggregation
(vasoconstrictor thromboxane A2 is an important platelet-derived stimulus that amplifies platelet aggregation, which leads to the formation of the primary hemostatic plug. Platelet contraction, an event that is dependent on the platelet cytoskeleton that creates an irreversibly fused mass of platelets, which constitutes the definitive secondary hemostatic plug)

Front 24

How does thrombin stabilise the platelet plug ?

Back 24

- Thrombin binds to a protease-activated receptor
- Thrombin converts fibrinogen to fibrin in the vicinity of the platelet plug, functionally cementing the platelets in place
-Noncleaved fibrinogen is also an important component of platelet aggregation. Platelet activation by ADP triggers a conformational change in the platelet GpIIb-IIIa receptors that induces binding to fibrinogen

Front 25

endothelial cell-derived prostaglandin PGI2 (prostacyclin) inhibits platelet aggregation and is a potent vasodilator; conversely, what is platelet-derived and activates platelet aggregation with vasoconstriction?

Back 25

- Prostaglandin TxA2

Front 26

At the conclusion of the proteolytic cascade, What converts the soluble plasma protein fibrinogen into fibrin monomers that polymerise into an insoluble gel. The fibrin gel encases platelets and other circulating cells in the definitive secondary hemostatic plug, and the fibrin polymers are covalently cross-linked and stabilised by factor XIIIa (which itself is activated by this molecule?

Back 26

- Thrombin

Front 27

The extrinsic pathway was so designated because it required the addition of an?

Back 27

- Exogenous trigger

Front 28

Intrinsic pathway only required exposing of what factor to thrombogenic surfaces

Back 28

- Factor XII (12)
(Hageman factor)

Front 29

Prothrombin time (PT) assay assesses the function of the proteins in the which pathways, containing which proteins?

Back 29

- Extrinsic pathway
(factors VII, X, II, V, and fibrinogen).

Front 30

Partial thromboplastin time (PTT) screens for the function of the proteins in the

Back 30

- Intrinsic pathway
(factors XII, XI, IX, VIII, X, V, II, and fibrinogen)

Front 31

List the three categories of endogenous anticoagulants?

Back 31

- Antithrombins
(inhibit the activity of thrombin and other serine proteases, including factors IXa, Xa, XIa, and XIIa. Antithrombin III is activated by binding to heparin-like molecules on endothelial cells)
- Proteins C and S
(vitamin K–dependent proteins that act in a complex that proteolytically inactivates factors Va and VIIIa. Protein C activation by thrombomodulin )
- TFPI
(a protein produced by endothelium (and other cell types) that inactivates tissue factor–factor VIIa complexes)

Front 32

Fibrinolysis is achieved by plasmin breaking down fibrin, what can be used in diagnosing abnormal thrombotic states including disseminated intravascular coagulation, deep venous thrombosis, or pulmonary embolism ?

Back 32

- Fibrin split products (FSPs or fibrin degradation products)

Front 33

Fibrinolysis is largely accomplished through the enzymatic activity of ?

Back 33

- Plasmin
(which breaks down fibrin and interferes with its polymerisation)

Front 34

Name two types of plasmin activation proteins?

Back 34

- Urokinase-like PA (u-PA)
- Tissue-type plasminogen activator (t-PA)

Front 35

What blocks fibrinolysis by inhibiting t-PA binding to fibrin and confers an overall procoagulant effect?

Back 35

- Plasminogen activator inhibitor
(released from endothelial cells)

Front 36

To prevent excess plasmin from lysing thrombi indiscriminately elsewhere in the body, free plasmin is rapidly inactivated by ?

Back 36

- α2-plasmin inhibitor

Front 37

Virchow's triad includes what three factors?

Back 37

- Endothelial injury
(AMI, over ulcerated plaques in atherosclerotic arteries, vasculitis
- Stasis or turbulent blood flow
(aneurysms, AMI, Rheumatic mitral valve stenosis, AF, Hyperviscosity, sickle cell anemia and vascular occlusions)
- Hypercoagulability of the blood
(point mutations in the factor V gene and prothrombin gene )

Front 38

Leiden mutation involves which factor?

Back 38

- Factor V (5)
(mutation results in a glutamine to arginine substitution at position 506 that renders factor V resistant to cleavage by protein C)

Front 39

A single nucleotide change (G20210A) in the 3′-untranslated region of what gene, in terms of hypercoagulablilty?

Back 39

- Prothrombin gene

Front 40

Heparin-induced thrombocytopenia (HIT) syndrome can be caused post the administration of what?

Back 40

- Unfractionated heparin
(which may induce the appearance of antibodies that recognize complexes of heparin and platelet factor 4 on the surface of platelets. Newer low-molecular weight heparin preparations induce antibody formation less frequently)

Front 41

What are the clinical manifestations of Antiphospholipid antibody syndrome?
most important pathologic effects are mediated through binding of the antibodies to epitopes on plasma proteins (e.g., prothrombin) that are somehow induced or “unveiled” by phospholipids. In vivo, these autoantibodies induce a hypercoagulable state by causing endothelial injury, by activating platelets and complement directly

Back 41

- Recurrent thromboses
- Repeated miscarriages
- Cardiac valve vegetations
- Thrombocytopenia

Front 42

What is the fate of the Thrombus?

Back 42

- Propagation
(accumulate additional platelets and fibrin)
- Embolisation
(Thrombi dislodge and travel to other sites in the vasculature)
- Dissolution
(fibrinolysis)
- Organisation and recanalisation
(Older thrombi become organized by the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts )

Front 43

Tumor-associated inflammation and coagulation factors (tissue factor, factor VIII) and procoagulants (e.g., mucin) released from tumor cells all contribute to the increased risk of thromboembolism in disseminated cancers, so-called

Back 43

- Migratory thrombophlebitis or Trousseau syndrome

Front 44

Fat embolism syndrome characterised by?

Back 44

- Pulmonary insufficiency
- Neurologic symptoms
- Anemia
(haemolysis)
- Thrombocytopenia
(diffuse petechial rash )
- Fatal in about 5% to 15% of cases
- Tachypnea
(1 to 3 days onset)
- Dyspnea
- Tachycardia
- Irritability
- Restlessness can progress to delirium or coma

Front 45

What volume of air is required to have a clinical effect in the pulmonary circulation?

Back 45

- 100 cc

Front 46

In caisson disease, persistence of gas emboli in the skeletal system leads to multiple foci of ischemic necrosis; the more common sites are ?

Back 46

- Femoral heads
- Tibia
- Humeri

Front 47

The rapid formation of gas bubbles within skeletal muscles and supporting tissues in and about joints is responsible for the painful condition called the ?

Back 47

- Bends

Front 48

In the lungs, gas bubbles in the vasculature cause edema, hemorrhage, and focal atelectasis or emphysema, leading to a form of respiratory distress called the ?

Back 48

- Chokes

Front 49

Amniotic fluid embolism has onset is characterized by sudden ?. If the patient survives the initial crisis, pulmonary edema typically develops, along with (in half the patients) DIC, as a result of release of thrombogenic substances from the amniotic fluid

Back 49

- Severe dyspnea
- Cyanosis
- Shock
- Neurologic impairment
(ranging from headache to seizures and coma)

Front 50

Infarcts are classified according to color and the presence or absence of infection; they are either ?

Back 50

- Red (hemorrhagic)
(lung and small intestine or in reperfusion post infarct)
- white (anemic)
(heart, spleen, and kidney)

Front 51

The effects of vascular occlusion can range from no or minimal effect to causing the death of a tissue or person. The major determinants of the eventual outcome are ?

Back 51

- The nature of the vascular supply
- The rate at which an occlusion develops
- Vulnerability to hypoxia
- The oxygen content of the blood

Front 52

Neurons undergo irreversible damage when deprived of their blood supply for only (1)? Myocardial cells, though hardier than neurons, are also quite sensitive and die after only (2) ?of ischemia. In contrast, fibroblasts within myocardium remain viable even after many (3)? of ischemia

Back 52

- (1) 3 to 4 minutes
- (2) 20 to 30 minutes
- (3) Hours

Front 53

The causes of shock fall into five general categories, what are they?

Back 53

- Cardiogenic shock
- Hypovolemic shock
- Septic shock
- Neurogenic shock
- Anaphylactic shock

Front 54

Toll-like receptors (TLRs, Chapter 2 ) recognise microbial elements and trigger the responses that initiate sepsis, what do inflammatory cells produce ?

Back 54

- TNF
- IL-1
- IFN-γ
- IL-12
- IL-18

Front 55

Name the complement proteins attaches to these; anaphylotoxins (1) , chemotactic fragments (2), and opsonins (3)

Back 55

- (1) C3a, C5a
- (2) C5a
- (3) C3b

Front 56

inflammatory mediators produced by leukocytes has three major sequelae, they are?

Back 56

- Thrombosis
- Increased vascular permeability
- Vasodilation

Front 57

Cytokines such as TNF and IL-1, stress-induced hormones (such as glucagon, growth hormone, and glucocorticoids), and catecholamines all drive what physiological process?

Back 57

- Gluconeogenesis

Front 58

Hyperglycemia decreases function of what leukocyte?

Back 58

- Neutrophil

Front 59

early nonprogressive phase of shock, a variety of neurohumoral mechanisms help to maintain cardiac output and blood pressure, they are?

Back 59

- Baroreceptor reflexes
- Catecholamine release
- Activation of the renin-angiotensin axis
ADH release
Generalised sympathetic stimulation
(The net effect is tachycardia, peripheral vasoconstriction, and renal conservation of fluid)