Hematology: Key Concepts from Lecture Transcript

Bone marrow, anemia, and transplantation

• Observation: bone marrow aspirate can be discussed alongside blood samples; sometimes the specimen discussed is bone marrow, other times blood. In context, aplastic anemia is diagnosed when the bone marrow shows no red blood cell precursors, indicating the bone marrow is the problem and not peripheral destruction or lack of nutrients.
• Anemia etiologies beyond marrow failure include iron deficiency and B-vitamin deficiencies that impair red blood cell production, or increased red blood cell destruction. When those causes are ruled out, clinicians may examine the bone marrow directly.
• Bone marrow transplant: can be performed by infusing bone marrow from a healthy donor into a patient who lacks a particular blood cell line to restore production.

Thalassemia and hemoglobin biology

• Thalassemia is a genetic disorder involving defective globin chain production in hemoglobin, not caused by environment (e.g., iron deficiency) but by a gene mutation transmitted from parent to child. Genetic counseling helps determine form and inheritance risk.
• Globin chains affected in thalassemia are the protein components of hemoglobin. If one chain is affected, the person may have mild anemia; if all four globin chains are affected, transfusions are often required.
• Clinical consequences of severe thalassemia include: enlarged spleen, bone deformities due to marrow expansion, growth issues, chronic weakness, and the need for regular transfusions; infants with severe forms may be stillborn. Lifespan can be shortened.
• Pathophysiology: the spleen enlarges because it tests and removes defective RBCs; skeletal changes arise from marrow expansion as the body tries to compensate for defective red cells.
• Reticulocytes (nucleated red blood cells) can appear in circulation when the marrow is stressed and releasing immature erythrocytes to meet demand. Typical mature RBCs have no nuclei.
• If bilirubin (a breakdown product of heme) rises excessively, it signals increased RBC destruction or impaired liver processing.

Jaundice, bilirubin metabolism, and liver function

• Bilirubin accumulation causes jaundice when red blood cells are destroyed faster than the body can process bilirubin or when the liver cannot process bilirubin effectively.
• The liver is where bilirubin processing occurs; when liver function is compromised, bilirubin clearance decreases, leading to jaundice.

White blood cells (WBCs) and differential basics

• Neutrophils are the most common WBCs and typically have segmented nuclei with granules. Lymphocytes are the second most common and are characterized by a large nucleus with relatively little cytoplasm; lymphocytes are central to antibody production.
• Elevations or reductions in specific WBC types can guide diagnostic thinking about ongoing infections, inflammation, or hematologic disorders.

Plasma components and osmotic balance

• Plasma carries nutrients and gases; plasma proteins are large molecules that cannot easily cross capillary walls, contributing to osmotic (colloid osmotic) pressure and fluid distribution.
• The three major plasma proteins are albumin, globulin, and fibrinogen. Because they are large, they are retained within the vasculature and generate colloid osmotic pressure that helps draw water back into capillaries.
• Osmosis and Starling forces (conceptual): hydrostatic pressure from the heart drives fluid out of capillaries, while colloid osmotic pressure from plasma proteins pulls water back in. In simple terms:
  \Pi_{col} \propto [\text{protein}]
  where the colloid osmotic pressure is largely due to albumin and other plasma proteins.
  The balance between hydrostatic pressure and oncotic (osmotic) pressure determines fluid movement between vessels and interstitial space.
• If albumin or other plasma proteins are reduced (hypoalbuminemia), edema can develop because water is less effectively pulled back into vessels.
• Example linked to liver disease: liver makes albumin; in liver disease, albumin production falls, leading to edema and sometimes ascites (fluid accumulation in the abdominal cavity).
• Ascites vs edema: edema refers to peripheral fluid accumulation (e.g., ankles, feet); ascites specifically refers to abdominal fluid accumulation.
• A clinical example: in a dog with liver disease, low albumin led to ascites, and occasionally fluid can be drained with a trocar to relieve diaphragmatic pressure and improve breathing.
• In congestive states (cardiac failure), reduced venous return and backup of fluid can cause pulmonary edema or pleural effusions; this reflects hydrostatic pressure effects.

Urea, kidneys, and BUN

• Urea is a byproduct of protein breakdown formed at a relatively steady rate; it is normally eliminated by the kidneys.
• Blood Urea Nitrogen (BUN) is a common lab metric used to assess kidney function. If kidney function declines, urea clearance decreases and blood levels rise, indicating potential renal dysfunction.

Electrolytes and intracellular–extracellular distribution

• Among electrolytes, potassium is highest intracellularly, while sodium is highest extracellularly (important for nerve conduction and muscle function).
• Calcium has multiple critical roles: bone mineralization (calcium phosphate matrix), vitamin D–mediated absorption, muscle contraction and nerve conduction, and blood clotting (coagulation).
• Calcium’s role in clotting is particularly important: calcium participates in several steps of the coagulation cascade and is necessary for proper clot formation.
• Magnesium, chloride, bicarbonate, and phosphate are also important in cellular function and acid–base balance, but the key takeaways here focus on calcium’s roles described above.
• Some clinical tidbits: reported associations between fibromyalgia and altered calcium handling in cells, which may relate to membrane permeability and calcium retention; this illustrates how fundamental ions influence nerve and muscle function.

Hemostasis and clot formation (coagulation cascade)

• Hemostasis consists of three main stages: 1) Vascular spasm (vasoconstriction) – smooth muscle in blood vessel walls contracts to reduce bleeding.
  • The relevant muscle type is smooth muscle (involuntary).
    2) Platelet plug formation – platelets adhere to damaged endothelium and aggregate to form a temporary plug.
    3) Coagulation cascade – a complex series of enzymatic steps that convert soluble fibrinogen into insoluble fibrin, forming a stable clot.
• Key takeaway for coagulation cascade (the main irreversible step):
  ext{Fibrinogen} \xrightarrow{\text{thrombin}} \text{Fibrin}
  where thrombin is produced in the cascade from prothrombin.
• Another essential step in the cascade (as discussed and simplified in class):
  \text{Prothrombin} \xrightarrow{\text{thrombin}} \text{Thrombin}
  Then thrombin converts fibrinogen to fibrin to form the clot.
• The cascade is complex with many factors; for exam purposes, the focus is on: platelets form a plug, and fibrinogen-to-fibrin conversion solidifies the clot. Calcium is a necessary cofactor in many of these clotting reactions.
• Clinical relevance: clotting factor deficiencies (e.g., hemophilia) can lead to excessive bleeding; historical examples include hemophilia in royal lineages due to factor defects.
• Before surgeries, clinicians measure clotting times (e.g., prothrombin time, thrombin time) to assess whether a patient can safely clot during the procedure.

Thrombus, embolus, infarction, and atherosclerosis

• Thrombus: an abnormal, pathologic blood clot that forms in a vessel. An embolus is a thrombus or other clot that travels through the bloodstream.
• Infarction: tissue death due to complete obstruction of a blood vessel, preventing blood flow to the tissue.
• Atherosclerosis: buildup of lipid-rich plaques in vessels, contributing to abnormal blood flow and increasing the risk of thrombus formation.
• Clinically, a deep vein thrombus (DVT) often forms in large peripheral veins (e.g., legs) and can travel to the lungs causing a pulmonary embolism; prolonged immobility (e.g., long flights) increases risk due to venous stasis.

Blood groups, antigens, and transfusion compatibility

• Blood type determined by surface antigens on red blood cells (RBCs). The major ABO antigens are A and B; individuals have one of four blood types: A, B, AB, or O.
• Antigens and antibodies:
  • An antigen in plasma-facing blood cells triggers antibody production if the immune system encounters a foreign antigen.
  • Type A RBCs have A antigen and anti-B antibodies in plasma.
  • Type B RBCs have B antigen and anti-A antibodies in plasma.
  • Type AB RBCs have both A and B antigens and no anti-A/anti-B antibodies.
  • Type O RBCs lack both A and B antigens and have both anti-A and anti-B antibodies in plasma.
• Transfusion compatibility:
  • A person with type A blood should not receive RBCs with B antigen (type B or AB blood would be problematic due to anti-B antibodies).
  • Type B individuals should not receive A antigen RBCs (anti-A antibodies would attack A antigens).
  • AB individuals can receive RBCs from A, B, AB, or O (universal recipient in ABO terms, though compatibility with Rh is separate).
  • O individuals are universal donors for ABO blood types because they lack A and B antigens; however, they have anti-A and anti-B antibodies that can react with donor blood if not properly matched for non-O recipients.
• ABO frequencies (qualitative): type O is the most common, followed by type A; type B is rarer, and type AB is the rarest.
• Transfusion reactions and signs of incompatibility: anxiety, breathing problems, facial flushing, headache, severe pain, and potentially jaundice due to rapid RBC destruction and bilirubin release.
• Visual aid concept: agglutination occurs when antibodies bind to incompatible antigens, causing RBC clumping; this is a critical diagnostic sign of a transfusion reaction.
• Practical takeaways for clinical practice:
  • Always determine recipient blood type and donor type compatibility before transfusion.
  • AB is the universal recipient, and O is the universal donor (for ABO compatibility).
  • Rh typing is not the focus of this lecture, but is another important compatibility factor in real-world transfusion medicine.

• Quick recap of key terms and concepts to memorize:
  • Aplastic anemia: bone marrow failure with absent red cell precursors; marrow is the problem.
  • Thalassemia: genetic defect in globin chain production; can cause mild to severe anemia and transfusion dependence; associated with splenomegaly and skeletal changes.
  • Reticulocyte: immature RBC with nuclei, released when marrow is responding to anemia; mature RBCs normally lack nuclei.
  • Jaundice: elevated bilirubin from increased RBC breakdown or impaired liver processing.
  • Colloid osmotic pressure: osmotic pressure from plasma proteins (albumin, globulin, fibrinogen) retaining water in vessels.
  • Edema and ascites: fluid accumulation due to hypoalbuminemia or other shifts in Starling forces.
  • Urea/BUN: indicator of kidney function and waste excretion.
  • Calcium roles: bone mineralization, vitamin D absorption, muscle contraction, nerve conduction, coagulation.
  • Hemostasis steps: vascular spasm, platelet plug formation, coagulation (fibrin formation).
  • Clotting cascade terminology: fibrinogen to fibrin; prothrombin to thrombin; calcium as a cofactor.
  • Thrombus vs embolus vs infarction; atherosclerosis as a risk factor.
  • ABO blood group system: A, B, AB, O antigens; corresponding antibodies in plasma; transfusion compatibility and common clinical signs of reactions.

ext{Fibrinogen}
ightarrow ext{Fibrin} ext{ (via thrombin)}
ext{Prothrombin}
ightarrow ext{Thrombin} ext{ (in the cascade)}
\Pi_{col} \approx k [\text{protein}] ext{ (colloid osmotic pressure from plasma proteins)}