Patho: disorders of hematopoietic function

module 3

Red Blood Cells aka

erythrocytes

RBC responsible for

oxygen delivery and CO2 removal

RBC lifespan

approx 120 days

Normal RBC lab value

4.5-6.0 mill cells/L

Hematocrit

percentage of total blood volume that is RBCs

Hematocrit lab value

37-52%

red blood cell production is called

erythropoiesis

RBC are produced in

bone marrow

Erythropoietin stimulates

bone marrow to produce RBCs

Erythropoietin is produced

by the kidneys

Hemoglobin (Hgb)

how RBC carry oxygen and CO2

1 Hgb molecule can carry

4 oxygen or CO2 molecules

Binding of oxygen to Hgb

Oxygen is breathed in and transported to alveoli

Diffusion allows for oxygen to move from the lungs to blood stream

Binds to Hgb molecule on RBC (oxy-Hgb) as it moves through pulmonary capillary

Carries O2 to the tissues

Picks up some CO2 to be brought back for exhalation

Normal Hgb lab value

12-18 g/dL

Destruction of RBCs in a healthy individual should be

equally matched with the production

Destruction of RBC is primarily facilitated in

the spleen, liver, bone marrow and lymph nodes.

when an old or defective RBC is identified, apoptosis is triggered and

the old or defective RBC is ingested and destroyed through the process of phagocytosis.

during RBC destruction, hemoglobin (heme) can be broken into

iron (transported back to bone marrow to be utilized in production of new hemoglobin molecules)

bilirubin (excreted by intestines as part of bile, excessive amts cause jaundice)

during RBC destruction, hemoglobin can be broken into globulin

Further broken down into amino acids which can be used for energy to create new proteins.

Anemia

RBC disorders that include blood loss, iron deficiency, and pernicious

Anemia etiology

dependent on the type of anemia

Anemia pathogenesis

↓ Circulating RBC’s, ↓ Hemoglobin (Hgb) Content, Abnormal Hgb

Or

Impaired Production, ↑ Destructing, Blood Loss

Anemia pathogenesis resulting in

Decreased Oxygen Carrying Capacity

Anemia clinical presentation

Weakness

Fatigue

Pallor

Syncope

Dyspnea

Tachycardia

Anemia diagnosis

CBC

Anemia treatment

dependent on the type of anemia

Blood loss anemia etiology

Bleeding – chronic or acute

Blood loss anemia clinical presentation

Orthostatic hypotension

↑ HR ↓ BP

↓ LOC

↓ Urine Output

Melena

Hematemesis

Blood loss anemia treatment

Stop Bleeding

Blood Transfusion (if Hgb <7)

Iron supplementation

Increasing dietary iron

Iron Deficiency etiology

Decreased Hgb production due to lack of iron (Fe)

Common in women of childbearing age, children <2, and the elderly

Inadequate intake of iron

Iron Deficiency clinical presentation

Hair Loss

Cheilitis

Glossitis

Pica

Splenomegaly

Iron Deficiency treatment

Iron supplementation

Increasing dietary iron

Pernicious Anemia etiology

Vitamin B12 deficiency

Inadequate intake of B12

Lack of intrinsic factor

Pernicious Anemia clinical presentation

Same as general anemia

Pernicious Anemia treatment

B12 supplementation

iron rich foods

Red meat, green leafy vegetables, organ meat

B12 rich foods

Meat & Dairy products

Cheilitis

inflammation of the lips

Glossitis

inflammation of the tongue

Intrinsic factor

protein produced by the stomach needed to absorb vitamin B12

acquired lack of intrinsic factor

portion of the GI tract removed or destroyed

autoimmune lack of intrinsic factor

body destroying parietal cells where intrinsic factor is produced

Platelets aka

thrombocytes

Platelets are responsible for

hemostasis (blood clotting)

normal platelet lab value

150,000 – 450,000 cells/mL

Hemostasis is a

physiological process that stops bleeding at a site of injury

3 stages of hemostasis

Vasoconstriction

Platelet Plug Formation

Coagulation

1) hemostasis begins with vasoconstriction triggered by vessel (endothelial) damage which leads to

decreased blood flow at the site of injury and increased blood pressure

2) platelets that are free floating through plasma recognize that injury has occurred because

when the vessel wall is damaged underlying connective tissue and collagen fibers are exposed

3) platelets then adhere to the vessel wall with the assistance of a plasma protein (von Willebrand factor)

partially activates the platelet causing it to change from a smooth shape cell a cell with multiple spiny spheres.

This also causes the platelet to release signaling molecules that call in reinforcements.

Essentially recruiting more platelets to the site

4) they begin to clump together (platelet aggregation)

platelet inhibitors that circulate through our body to prevent platelet aggregation from occurring to rapidly or frequently.

5) coagulation which is the last phase of hemostasis is said to occur as a cascading event bc one event prompts the next

Extrinsic – meaning it is triggered by trauma to vessel (faster)

Intrinsic – meaning it begins within the bloodstream, being triggered by internal damage to the vessel wall (slower)

common - prothrombin to thrombin, fibrinogen to fibrin

regardless of the pathway the cascade is dependent on many clotting factors including calcium and vitamin K

These clotting factors are primarily synthesized and secreted by the liver

patients with deficiencies of Vit K or liver failure are at risk for bleeding disorders to develop

At the end of the clotting cascade both these pathways come together in what we call the common pathway as the terminal steps in stable clot formation are the same

Clotting factor X activates and converts prothrombin (enzyme that helps blood to clot) into thrombin

Thrombin then causes conversion of fibrinogen into fibrin which is needed to stabilize the clot

clot dissolution and clot retraction occurs 20-60 minutes after clot formation

Platelets squeeze serum from clot

Pulling vessel edges together

Fibrinolysis is aka dissolution

Plasminogen in converted to plasmin

Plasminogen activators

Digests fibrin strands and clotting factors

Thrombocytosis

a state in which our platelet count is greater than 450,000.

Primary thrombocytosis also referred to as essential thrombocythemia occurs when

abnormal cells in the bone marrow initiate increased platelet production.

secondary thrombocytosis is caused by

another condition such as anemia, cancer, inflammation or infection, or surgery

Thrombocytosis risk factors

smoking, high cholesterol, and oral contraceptives

Thrombocytosis clinical manifestations

many patients do not experience clinical manifestations until after the platelet count has increased significantly and resulted in the development of a deep vein thrombosis (DVT) or pulmonary embolism (PE).

Thrombocytosis treatment

Medications

Plateletpheresis (donation)

Thrombocytopenia

A disorder of too few, not enough, platelets

Thrombocytopenia etiology

Decreased production

Increased destruction

Drug induced (heparin, aspirin)

Immune induced - ITP

Thrombocytopenia pathogenesis

Platelets > 150,000

Thrombocytopenia clinical presentation

Fatigue

Petechiae

Purpura

Ecchymosis

Bleeding – Nose, Mouth, GI tract

Factor V Liden

Thrombophilic genetic disorder that causes hypercoagulability

Factor V Liden etiology

Genetic mutation

Increases clotting risk x7

Factor V Liden pathogenesis

Impacts the factor V in the clotting cascade causing more coagulation

Thrombi form most commonly in the venous system

Resulting in DVT or PE

Factor V Liden clinical presentation

Deep Vein Thrombosis (DVT)

Pulmonary Embolism (PE)

Factor V Liden diagnosis and treatment

Diagnosis:

Lab Testing

Genetic Screening

Treatment:

Anticoagulant Therapy

Hemophilia & von Willebrand Disease

Genetic coagulation disorder that causes bleeding

Hemophilia & von Willebrand Disease etiology

Genetic mutation

Different types (A, B…)

Lack clotting factors needed to from clots

Hemophilia & von Willebrand Disease pathophysiology

Without all clotting factors blood clots are unable to form

Resulting in bleeding that does not stop

Hemophilia & von Willebrand Disease clinical presentation

Bleeding

Trauma / injury

GI

Bruising

Hemophilia & von Willebrand Disease diagnosis and treatment

Diagnosis:

Lab Testing

Genetic Screening

Treatment:

Medication

Factor replacement

Desmopressin (DDAVP)

systemic symptoms of bleeding

Tachycardia

Hypotension

Pallor

Syncope

Changes in LOC (hypoxia)

Disseminated Intravascular Coagulation (DIC)

Disorder of both clot formation and bleeding that is seen in critically ill patients

DIC caused by

high volume blood loss, sepsis, trauma (burns)

DIC can lead to

organ failure

DIC pathophysiology

abnormal production of clotting factors and fibrinolysis factors

DIC clinical manifestations

Signs of bleeding: oozing around IV sites, petechiae, bleeding gums, spontaneous GI bleeding

Development of microthrombi: disrupting blood flow to heart, lungs and kidneys

DIC treatment

blood products, fluids, critical care

DIC prognosis

20% - 50% mortality rate