Class notes

Introduction to Pathology and Molecular Medicine

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Course
PATH310 (PATH310)

Institution
Queen’s University (QU )

Notes for all modules including the following topics: -Blood disorders: Hemostasis, Hemophilia, & Thrombophilia -Cardiovascular disorders: Atherosclerosis & Channelopathies -Cancer: Chronic Myeloid Leukemia + Acute Myeloid Leukemia -Exposure-based disorders: Cervical cancer + Creutzfeldt-Jakob...

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Uploaded on July 1, 2024
Number of pages 108
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pathology
molecular medicine
introduction to pathology and molecular medicine

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Disease paradigm framework
Tuesday, April 19, 2022 12:40 PM

PATH 310 Page 1

,Module 1- Blood disorders: Hemostasis, Hemophilia, &
Thrombophilia
Monday, January 10, 2022 2:10 PM

⚫ DISEASE PARADIGM FRAMEWORK

What's known about how the disease develops
Alterations to biochemical
pathways useful in identifying Types of structural alterations that can be helpful in
affected or susceptible people identifying affected or susceptible people and may be
and/or can serve as a basis for useful to serve as a basis for treatment
treatment
Various types of methods to Overall impact of the disease on the functioning organ/tissue central to the disorder
identify affected or
susceptible people and/or to
select an appropriate
treatment for the disorder Likely outcome of the disease for the patient

Options for managing those
that have the disease What are the short or long-term effects of having the disease

○ Information obtained from testing can be integrated with knowledge about normal processes/pathways to detect what's affecting the patient and wh
the next steps are for treatment
▪ How much do genetic vs. environmental risk factors impact patient prognosis and treatment if diagnosed in early vs. late stages of the disease
▪ How can different mutations lead to the same disease while similar mutations lead to different diseases in different patients?
▪ Is it practical to screen susceptible people while they are asymptomatic or more beneficial to wait until they show signs of a disease?

Section 1- Hemostasis

⚫ INTRODUCTION TO HEMOSTASIS
○ Hemostasis: how the blood and vasculature typically maintain blood in a fluid state and respond to injury under normal physiological conditions to st
bleeding
○ Requirements of hemostasis:
➢ Rapid - process of preventing blood loss should occur as soon as the wound is created
➢ Controlled- response must be tightly regulated so It can be turned on/off when appropriate
➢ Site-specific - process should only happen at the site of the wound
➢ Limited - blood clot should then dissolve when no longer needed

⚫ Balancing two states: Procoagulant and Anticoagulant
○ Maintaining blood in a fluid state, with the ability to coagulate when needed, is important for a healthy cardiovascular system
○ Hemostasis requires balance between procoagulant and anticoagulant states
➢ Procoagulant
▪ Promotes wound healing and prevention of blood loss, and involves:
- Endothelial damage
- Platelet activation
- Coagulation activation
➢ Anticoagulant
▪ Needed to prevent thrombosis (formation of blood clot in a blood vessel) and involves:
- Anticoagulant factors
- Fibrinolytic factors
- Healed endothelium

PATH 310 Page 2

,⚫ Key elements of hemostasis
○ 2 key elements: BLOOD AND VASCULAR ENDOTHELIUM
➢ Components of blood
▪ Liquid component
- Plasma plays a role in the transport of proteins, hormones, electrolytes, organic nutrients, and waste products
◊ Some of these proteins include coagulation factors that play an important role in hemostasis
▪ Cellular components
- Include platelets, erythrocytes, and leukocytes
◊ Platelets account for <1% of total blood volume, but play an important role in initiating hemostasis
◊ When there is an intact endothelium (no vessel injury), platelets are in a quiescent state

➢ Vascular endothelium
▪ Monolayer of endothelial cells that produces factors (nitric oxide, prostacyclin) under resting conditions that prevent inappropriate
initiation of hemostasis
▪ The vascular endothelium separates the blood from procoagulant factors found in the subendothelial layer (contains the extracellular
matrix, smooth muscle cells, and factors such as collagen, von Willebrand factor, and tissue factor)
▪ Disruption of the vascular endothelium plays a role in initiation of hemostasis, since upon injury, blood is in direct contact with these
procoagulant factors, and the process of platelet plug formation begins

⚫ Three stages of hemostasis
1. Primary hemostasis
✓ Vasoconstriction
✓ Formation of a platelet plug
2. Secondary hemostasis
✓ Coagulation cascade- the process that produces fibrin (Factor 1a), resulting in the formation of a hemostatic plus
3. Tertiary hemostasis
✓ Fibrinolysis - process that degrades fibrin to break down the hemostatic plug
✓ Regulatory mechanisms

⚫ Primary hemostasis
○ Initiated by the disruption of the endothelial lining, resulting in the exposure of the subendothelium
➢ Vasoconstriction
▪ When a vessel injury occurs, a vasoconstriction reflect initiates at the site of injury
- It is a physiological response to decrease the amount of blood loss from the site early on
▪ The damaged endothelial cells further trigger this vasoconstriction response through the release of factors such as endothelin

PATH 310 Page 3

, ➢ Platelet plug formation
▪ Other factors released from the endothelial layer include von Willebrand factor (vWF), which binds to collagen in the exposed subendothelium
▪ Circulating platelets contain receptors for vWF resulting in platelet adhesion to these sites
▪ Bound platelets become activated and undergo a change of shape, leading to release of granules and their contents to help recruit additional
platelets to the site of injury
▪ Result: an aggregate of platelets, forming the platelet plug

⚫ Secondary hemostasis
○ The platelet plug formed in primary hemostasis is unstable, creating only a temporary seal and requires reinforcement to remain intact throughout th
healing process
○ Secondary hemostasis involves a sequence of reactions called the coagulation cascade, which results in the formation of fibrin and thus the formatio
of the hemostatic plug

Hemostatic plug

○ Components of a hemostatic plug
▪ Comprised mainly of fibrin
- Cross-linked fibrin mesh (yellow) stabilizes the platelet plug (grey) and traps erythrocytes (red) and leukocytes (green), resulting in a
stronger seal
- Hemostatic plug prevents blood loss while the vessel repairs itself

⚫ Coagulation cascade

Activation occurs in this way, a
continues as a cascade

PATH 310 Page 4

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