Neurological symptoms due nerve demyelination and neuron death

1N5315 Advanced Pathophysiology
Hematologic System
Core Concepts and Objectives with Advanced Organizers

Hemostasis
1. Analyze the process of hemostasis:
a. Analyze the platelet structure and the 4 phases of platelet plug formation:



sol-gel zone	Middle layer of the platelet. Provides structural support.

	● Thromboxane A2 o Product of the arachidonic acid pathway but is stored inside of the platelet too.

·Extrinsic Pathway – It’s considered the primary pathway of coagulation, the extrinsic pathway needs tissue factor (therefore needs tissue damage) in order to occur and to produce clotting; the extrinsic pathway has to have tissue factor in order to activate the other clotting factors;
·Intrinsic Pathway – the intrinsic pathway can occur without damage. It will occur when you take blood and put it in a glass vial (anionic surface). This will immediately cause the blood to clot (It is a parallel pathway for thrombin activation by factor XII) the intrinsic pathway just always has the factors it needs present in the blood

·Contributions from both the extrinsic and intrinsic pathways are necessary for maximal induction of factor Xa and effective clotting

Plasma Proteins
Tissue Factor

	Activates Prothrombin through activated Xa form
Prothrombinase Complex

	cleaves the extracellular domain of G-protein–coupled protease-activated receptors (PARs), thereby initiating transmembrane signaling.
Fibrinogen

	Fibrin – stabilizing factor – cross links fibrin through XIIIa to strengthen clot
XII

	IXa is a component of tenase complex, activates factor X
Antithrombin

		How is Coagulation altered?
Aspirin
	continue to prevent platelet aggregation	N/A

	N/A	INHIBITS THE COAGULATION PROCESS THROUGH BINDING TO ANTITHROMBIN (AT) VIA PENTASACCHARIDE SEQUENCE

TTP	Thrombotic microangiopathy in which platelets aggregate and cause occlusion of arterioles and capillaries within the microcirculation. Treatment by replacement with FFP and steroid administration. Some may need splenectomy, but post op bleeding is a major complication.
		FACTOR VIII DEFICIENCY-A MUTATION-THE ALTERED OR MISSING PROTEIN CAN NOT PARTICIPATE IN THE

		Example
Coagulopathy Hemorrhage
		Related to decrease in the total number of platelets.

c.

Hageman Deficiency.


Hemophilia A	Classic Hemophilia.	Persistent bleeding from minor trauma Hemorrhage into the joints causes pain, limited joint mobility, and increase risk of degenerative joint changes.
		Bleeding only after	Caused by factor IX deficiency

f.

- autosomal dominant, heterozygotes have 50-60% of normal levels
-

by late teens - early 20s:

- 75% of these events occur

spontaneously; 25% r/t

cutaneous vessels w/

large areas of skin

immunologic activity of protein C

a. caused by entire gene deletion

thrombophilia)

- autosomal dominant, heterozygotes have 50-60% of normal levels

thrombophlebitis

- PE

spontaneous thrombi dev

2 types:

1. type I: quantitative
deficiency → low levels of protein S and activity


Factor V Leiden
		- clot forms		- accumulation of clotting factors & platelets → thrombus formation in vein (often near venous valve - inflammation around thrombus promotes further platelet aggregation → thrombus propagates or grows

6. Evaluate the etiology, clinical manifestations and pathophysiology of select red blood cell disorders.
g. Differentiate between macrocytic, microcytic and normocytic anemias and give an example of each anemia.

i. Macrocytic Anemia (Megalobastic: MCV = greater than 100)
1. Most common forms:
a. Pernicious Anemia (Pernicious = highly destructive)
i. Reduction in the amount of RBC caused by Vitamin B12 deficiency caused by a lack of intrinsic factor which results in malabsorption of Vitamin B12.

Iron
Deficiency

● Poverty
● Women of childbearing

● Most common causes

related to chronic blood loss

o Occult bleeding in

GI tract

have higher incidence than

community

o Rheumatoid Arthritis

o Chronic Hepatitis

Hemolytic
Disease of
the Newborn

o ABO blood

first fetus, but

o Can occur only if antigens on

incompatibilities exist if

Mild HDN:

Red Cell Disorders	Pathophysiology

	It’s a reduction in RBC’s secondary to deficiency in folic acid
Iron Deficiency


	Genetic autosomal recessive disease When there is a lack of oxygen, the HbS

● *leukocytes—white blood cells or leukocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders.

● *neutrophils—are the most abundant type of granulocytes and the most abundant (40-75%) type of white blood cells. They are a type of phagocyte and are the first responders of inflammatory cells to migrate towards the type of inflammation. They are predominant in the pus, thus the whitish/yellowish appearance.

TERMS THAT WE WERE ASKED TO KNOW IN THE LECTURE AND CAUSES

1. Leukocytosis—refers to an increase in the number of total WBC. This occurs as a normal protective response to physiologic stressors, such as infection, strenuous exercise, emotional changes, temperature changes, anesthesia, surgery, pregnancy, and some drugs, hormones and toxins. Can be caused by pathologic conditions, such as malignancies and hematologic disorders.

**increased number of circulating granulocytes (neutrophils, eosinophils, basophils) and monocytes are primarily a response to infection. Decreased numbers occur when infectious processes exhaust the supply of circulating granulocytes and monocytes by drawing them out of the circulation and into infected tissues faster than they can be replaced. Decreases also can be caused by disorders that suppress marrow function.

**KNOW TABLE 29-1 ON PAGE 1010**