PHYSIO-SQ3

RBC Lipid Bilayer: Ankryn

anchoring protein,

Ensures the cytoskeleton is attached to the plasma membrane.

Helps maintain the biconcave shape of RBCs.

RBC Lipid Bilayer: Spectrin

• Ensures the cytoskeleton is attached to the plasma membrane.

• Helps maintain the biconcave shape of RBCs.

Iron in the Body: Transferrin

transport form

Iron in the body: Ferritin

storage form

Iron in the Body: Absorption

absorbed from the small intestine, primarily duodenum

Role of Hepcidin: Found in

Liver

Role of Hepcidin: Correlation

provides a link between inflammation and anemia

Role of Hepcidin: Inhibits

ferroportin

RBC Phagotization: Bone Marrow & Spleen

Macrophages

RBC Phagotization: Liver

Kupffer Cells

Hemoglobin concentration (Hb)

How much hemoglobin (the protein in red blood cells that carries oxygen) is in your blood.

Hematocrit (Hct)

The percentage of your blood that is made up of red blood cells

Red Blood Cell Count (RBC Count)

The number of red blood cells in a tiny drop of blood

Mean Corpuscular Volume (MCV)

The average size of your red blood cells.

Mean Corpuscular Hemoglobin (MCH)

The average amount of hemoglobin inside each red blood cell.

Mean Corpuscular Hemoglobin Concentration (MCHC)

The average concentration of hemoglobin in the red blood cells.

Hemolytic Anemia: Hereditary spherocytosis

Defective Cytoskeleton

Hemolytic Anemia: Hemoglobinopathy (sickle cell disease)

Genetics, Deformed blood cell

CLINICAL PICTURE OF ANEMIA: Lab Results

High Reticulocytes: Low Hemoglobin & Hematocrit

BLOOD LOSS ANEMIA: Acute

body replaces only the plasma → low RBC concentration

BLOOD LOSS ANEMIA: Chronic/ microcytic, hypochromic anemia

body cannot absorb iron fast enough → small RBCs with little hemoglobin

DISORDERED PRODUCTION: Aplastic anemia

lack of functioning bone marrow → Low production of RBCs

DISORDERED PRODUCTION: Megaloblastic anemia:

oversized, bizarrely-shaped, fragile RBCs → Due to deficiency of vitamin B12 or B9 → Improperly maturing RBCs

POLYCYTHEMIA VERA / ERYTHREMIA

Abnormal blast cells; don’t stop producing RBCs. Low EPO

POLYCYTHEMIA VERA: Behavior of Progenitor cells

uncontrollably dividing even though the EPO is low

SECONDARY POLYCYTHEMIA

Physiologic adaptation to hypoxia, High EPO

Agglutinogen:

antigens present on the cell membrane of RBCs

Agglutinin:

antibodies that attack foreign agglutinogens

Agglutination:

antibodies attack RBCs with indicated antigen, causing clumping

RBC Indices: MCV

microcytic ↓, normocytic ↔ , macrocytic ↑

RBC Indices: MCHC

hypochromic ↓, normochromic ↔, hyperchromic ↑

RBC Indices: Reticulocyte count

marker of bone marrow activity.

RBC Abnormalities: Change in size

anisocytosis, macrocytes, microcytes

RBC Abnormalities: Change in shape

poikilocytosis, echinocytes, schistocytes

RBC Abnormalities: Change in color

hypochromic cells, spherocytes, target cells

RBC Abnormalities: Immature cells

normoblasts, megaloblasts, reticulocytes

Mechanisms of Hemostasis: Injury

A blood vessel is severed. Blood and blood components (e.g., erythrocytes, white blood cells, etc.) are leaking out of the breaks.

Mechanisms of Hemostasis: Vascular spasm

The smooth muscle in the vessel wall contracts near the injury point, reducing blood loss.

Mechanisms of Hemostasis: Platelet plug formation (Primary Hemostasis)

Platelets are activated by chemicals released from the injury site with underlying collagen

Mechanisms of Hemostasis: Coagulation (Secondary)

In coagulation, fibrinogen is converted to fibrin, which forms a mesh that traps more platelets and RBC producing a clot.

Platelet Plug Formation Adhesion: GPIa/IIa (Integrin α2β1)

First receptor to help platelets stick (binds directly to collagen in the exposed vessel wall)

Platelet Plug Formation Adhesion: GPVI

• Works alongside GPIa/IIa to bind collagen and activate platelets.

• Key action: Helps trigger platelet activation

Platelet Plug Formation Adhesion: GPIb-IX-V Complex

The main adhesion receptor for von Willebrand Factor

Platelet Plug Formation Adhesion:von Willebrand Factor (vWf)

Acts as a bridge between exposed collagen and platelet receptor GPIb (part of GPIb-IX-V)

Platelet Plug Formation Adhesion: GPIc/IIa

Binds Fibronectin & Laminin: additional support for adhesion.

Platelet Plug Formation Activation:

Binding of ligand triggers conformational change in platelet receptors that initiates an intracellular signaling cascade

Platelet Plug Formation Activation:Phospholipase C (PLC)

• Enzyme activated in the signal cascade.

• Action: Generates signals that cause Ca²⁺ to enter the platelet

Platelet Plug Formation Activation: Calcium (Ca²⁺)

Acts as a key intracellular messenger.

• Action: Triggers platelet shape change, granule release, and activation of other enzymes. Supports clotting reactions.

Platelet Plug Formation Activation: ADP & ATP

Recruit and activate more platelets.

Platelet Plug Formation Activation: Serotonin

Helps blood vessels constrict to reduce bleeding.

Platelet Plug Formation Activation: Alpha Granules (Fibrinogen)

Strengthen the platelet plug and support clot formation.

Platelet Plug Formation Activation: Cyclooxygenase (COX)

Enzyme that converts arachidonic acid into TXA₂.

Platelet Plug Formation Activation: Thromboxane A₂ (TXA₂)

Promotes platelet aggregation (platelets stick together) and vasoconstriction.

Platelet Plug Formation Aggregation:

Signaling molecules released by activated platelets amplify the platelet activation response

Platelet Plug Formation Aggregation: ADP

Binds to P2Y₁₂ receptors on other platelets → activates and recruits them to the growing plug.

Platelet Plug Formation Aggregation: Serotonin

Helps cause vasoconstriction (narrowing of vessels) and supports platelet activation

Platelet Plug Formation Aggregation: Thromboxane A₂ (TXA₂)

Strong promoter of platelet activation and aggregation + vasoconstriction.

Platelet Plug Formation Aggregation: Fibrinogen

Action:

• Forms bridges between platelets by binding to activated GPIIb/IIIa receptors.

• Later, when cleaved by thrombin, it becomes fibrin → creates a stable clot (secondary hemostasis).

Platelet Plug Formation Aggregation: GPIIb/IIIa Receptor

• Role: Resting state = inactive.

• Upon activation: Undergoes a shape change → can now bind fibrinogen.

Platelet Plug Formation Aggregation: Thrombin

Role in later phase (secondary hemostasis): Converts fibrinogen → fibrin, which “cements” and stabilizes the platelet plug into a clot.

Antiplatelet Agents: Aspirin

Blocks thromboxane A₂ formation → less platelet activation.

Antiplatelet Agents: Clopidogrel

Blocks P2Y₁₂ receptors → ADP can’t activate platelets effectively.

Coagulation Cascade: Factor Xa

The point at which the extrinsic and the intrinsic pathways of the coagulation cascade meet.

Coagulation Cascade: Extrinsic Pathway

Tissue activation/activator pathway

Extrinsic Pathway Vessel Trauma : Key Player/s

Tissue Factor (Factor III / tissue thromboplastin)

Extrinsic Pathway Tissue Factor Complex Formation : Key Player/s

Factor VII (inactive → VIIa): A zymogen that becomes activated.

Calcium (Ca²⁺/Fa.IV): Cofactor that stabilizes the complex.

Role: The TF–VIIa–Ca²⁺ complex activates Factor X → Factor Xa.

Extrinsic Pathway Factor X Activation : Key Player/s

Character: Factor X (activated to Xa by TF–VIIa–Ca²⁺).

Role: Central step — Factor Xa enters the common pathway.

Extrinsic Pathway Prothrombin Activator Formation : Key Player/s

Factor Xa: The active protease.

Phospholipids: Provide a surface for assembly of the complex.

Factor V (initially inactive): Cofactor that helps accelerate thrombin generation.

Role: Together they form the Prothrombinase Complex, which converts Prothrombin (Factor II) → Thrombin (IIa).

Extrinsic Pathway Positive Feedback: Key Player/s

Thrombin (Factor IIa): Protease that cleaves fibrinogen → fibrin later on.

Factor Va: Activated form of Factor V, greatly accelerates prothrombin activation.

Role: Amplifies thrombin production (positive feedback loop)

Intrinsic pathway: Key Player/s

Blood contact with exposed endothelial collagen triggers a cascade of reactions

Intrinsic pathway Initiation (contact phase): Key Player/s

• Factor XII (Hageman factor) → becomes XIIa.

• High Molecular Weight Kininogen (HMWK) → cofactor, anchors XII to surface.

• Prekallikrein → Kallikrein (via XIIa).

• Roles:

  • XIIa starts the cascade.

  • HMWK stabilizes the process.

  • Kallikrein accelerates conversion of more XII → XIIa (positive feedback).

Intrinsic pathway Factor XI Activation: Key Player/s

Factor XIa + Ca²⁺.

Role: Prepares to activate Factor IX.

Intrinsic pathway Factor IX Activation: Key Player/s

Factor IXa.

Role: Central enzyme for forming the tenase complex.

Intrinsic pathway Factor VIII Activation: Key Player/s

Factor VIIIa (a cofactor, not an enzyme).

Thrombin (from small amounts already formed) → boosts VIII activation (positive feedback).

Role: Cofactor needed for tenase formation.

Intrinsic pathway Tenase Complex Formation: Key Player/s

Character: Tenase Complex. (F.IX + F.VIII)

Role: Converts Factor X → Xa.

Intrinsic pathway Transition to Common Pathway: Key Player/s

Factor Xa joins Factor V + Ca²⁺ + phospholipid → forms Prothrombinase Complex.

Role: Converts Prothrombin → Thrombin, just like in the extrinsic pathway.

Fibrinolysis: Plasminogen

What it is: Inactive precursor circulating in the blood.

Role: Must be converted into plasmin to begin clot breakdown.

Fibrinolysis: Tissue Plasminogen Activator (tPA)

Role: Converts plasminogen → plasmin (main trigger of fibrinolysis).

Note: Released by Injured Tissues— Acts mainly when the clot is fully formed.

Fibrinolysis: Urokinase-type Plasminogen Activator (uPA)

Alternative activator of plasminogen → plasmin
Note: Important in tissues outside the vasculature.

Fibrinolysis: Fibrin

Role: Accelerates the conversion of plasminogen → plasmin.

Note: Ensures that fibrinolysis happens right at the clot site.

Fibrinolysis: Plasmin

Active protease derived from plasminogen.

Role: The main “clot-buster.” Halts coagulation cascade + dissolves the clot.

Anticoagulants: Prostacyclin

Promotes vasodilation → inhibits platelet activation and clotting

Anticoagulants: Nitric oxide

Inhibits platelet adhesion and aggregation

Anticoagulants: Tissue factor pathway inhibitor (TFPI)

Blocks protease activity for Factor VIIa

Anticoagulants: Antithrombin III (ATIII)

Binds to and inhibits Factor Xa and thrombin

Anticoagulants: Thrombomodulin

Forms a complex with thrombin to remove thrombin from the circulation and inhibit coagulation

Anticoagulants: Protein C and Protein S

Protein S acts as a cofactor in the function of Protein C that will inactive clotting factors involved in the intrinsic pathway

Anticoagulants: Protein C complex

Inactivate Factors Va and VIIIa

Anticoagulants: Heparin

Binds with antithrombin III to remove thrombin

Removes activated factor IX-XII

Anticoagulants: Warfarin

inhibits Vitamin K Epoxide Reductase (VKOR)→ Stops Vit K

Vitamin K dependent clotting factors:

II, VII, IX, X (27910)

Common Pathway Key Players: Factor X → Factor Xa

With Factor V + Ca²⁺ + phospholipid, forms the prothrombinase complex

Common Pathway Key Players: Factor V → Factor Va

Converts Prothrombin (II) → Thrombin (IIa).

Common Pathway Key Players: Factor II (Prothrombin) → Thrombin (IIa)

Converts Fibrinogen (I) → Fibrin monomers.

Activates Factor XIII → XIIIa.

Common Pathway Key Players: Factor I (Fibrinogen) → Fibrin

Soluble plasma protein converted by thrombin into insoluble fibrin monomers.

Common Pathway Key Players: Factor XIII (Fibrin-stabilizing factor) → XIIIa

Cross-links fibrin polymers → forms a stable fibrin mesh that traps platelets and blood cells, completing the clot.

Factor V → Factor Va: Activated by

Thrombin (Posititve Feedback)

Factor XIII (Fibrin-stabilizing factor) → XIIIa: Activated by

Thrombin with Ca+2

Hemophilia/ Classic hemophilia or hemophilia A

NO spontaneous bleeding occurs except after trauma

Hemophilia/ Classic hemophilia or hemophilia A: Cause

caused by an abnormal or deficient factor VIII