Blood Disorders, Hematology & Cardiovascular Overview

Erythrocytes (RBCs)

• Anatomy & physiology

  • No nucleus; biconcave discs ➜ ↑ surface area, flexibility
  • Filled with hemoglobin (Hb) for O₂ transport & CO₂ removal
  • Kidney senses arterial hypoxia → releases erythropoietin (EPO) → stimulates bone-marrow erythropoiesis
  • ↓ RBC count → tissue hypoxia; cycle up-regulates until O₂ restored

• Complete blood count (CBC) key numbers (facility ranges vary)

  • \text{Hemoglobin (Hgb)}: 14-18\,\text{g/dL (male)},\;12-16\,\text{g/dL (female)}
  • \text{Hematocrit (Hct)}: 42-52\%\,(M),\;37-47\%\,(F) (packed-cell volume)
  • \text{Mean Corpuscular Volume (MCV)}: 80-100\,\text{fL} (size)
  • \text{Mean Corpuscular Hb (MCH)} = mass of Hb per RBC
  • \text{MCHC} = Hb concentration (color / chromic)
  • \text{WBC}: 5{,}000-10{,}000\,/\mu L (↑ = infection; ↓ = leukopenia)
  • \text{Platelets}: 150{,}000-400{,}000\,/\mu L

Anemia – General Framework

• Etiology buckets

  1. ↓ Production
     • Nutrient lack (iron, B₁₂, folate)
     • ↓ EPO (kidney disease)
     • Alcohol → folate loss
  2. ↑ Destruction (hemolysis) • Abnormal shape – e.g.
     • Sickle-cell (HbS)
     • Thalassemia
  3. Blood loss
     • Hemorrhage, heavy menses, GI bleed, etc.

• Morphologic classification (MCV-based)

  • Normocytic (MCV 80-100) – normal size, just fewer cells
  • Microcytic (< 80) – small cells; examples: iron deficiency, thalassemia
  • Macrocytic (> 100) – large cells; examples: B₁₂ deficiency (pernicious), folate deficiency, alcohol-related

• Cardinal symptoms (all anemias)
  Fatigue, dyspnea, pallor, cold intolerance, dizziness, tachycardia, pallor of skin/conjunctiva.

Specific Anemias

1. Iron-Deficiency Anemia (IDA)

• Most common worldwide; microcytic-hypochromic
• Iron physiology metaphor: Ferritin is the “cookie tin” storing iron in liver; Transferrin is the “transport van”
• Causes
  • Inadequate intake : vegan diet, malnutrition
  • ↑ Demand : pregnancy, growth spurts
  • Malabsorption : celiac, Crohn’s, gastrectomy
  • Chronic blood loss : ulcers, gastritis, colon cancer, hemorrhoids, menorrhagia, NSAIDs/anticoagulants
• S/Sx: Hair loss, brittle nails, pica, glossitis, restless legs, HA, cold sensitivity

2. Aplastic Anemia

• Bone-marrow failure → pancytopenia (RBC, WBC, platelets)
  Definition: “Bone marrow stops producing all cells.”
• Etiology: radiation, chemo, toxins, drugs, autoimmune, viral
• Manifestations: fatigue (anemia), infections (neutropenia), bleeding (thrombocytopenia)
• Tx: immunosuppression, transfusion, stem-cell or marrow transplant

3. Vitamin B₁₂ (Cobalamin) Deficiency

• Macrocytic; often pernicious anemia (lack intrinsic factor from gastric parietal cells)
• Other causes: strict vegan, alcoholism, malabsorption (Crohn’s, bacterial overgrowth), post-gastrectomy/sleeve
• Unique neuro findings: peripheral neuropathy (paresthesia), memory loss, depression, ataxia
  Mnemonic: “B for Brain” symptoms.
• Tx: oral/high-dose B₁₂ or monthly IM injections

4. Folate Deficiency

• Macrocytic; diet poor in greens, alcoholism, ↑ demand (pregnancy), antifolate drugs (e.g. methotrexate)
• Differs from B₁₂: no neuropathy

5. Sickle-Cell Disease

• Autosomal recessive HbS; RBCs sickle under stress (illness, hypoxia) → occlusion & ischemic pain crises
• No cure; prevention & symptomatic control (oxygen, hydration, opioids)
• Crisis ⇒ organ ischemia, acute chest, stroke risk

6. Megaloblastic Anemia (umbrella)

• Caused by B₁₂ or folate deficiency ➜ large, immature RBCs

Platelets & Coagulation

• Platelet basics

  • Normal 150\,000-400\,000/\mu L; lifespan 7-10 days
  • Function: adhere to injury → primary hemostatic plug
  • Spleen sequesters & destroys aged platelets; post-splenectomy ➜ thrombocytosis

• Quantity disorders

  • Thrombocytopenia (< 100 K)
    • Causes: chemo, heparin-induced, autoimmune (ITP), marrow failure, alcoholism
    • Manifestations: bleeding gums, petechiae, purpura
  • Thrombocytosis (> 750 K)
    • Primary (essential) – marrow overproduction
    • Secondary – reaction to iron-def anemia, cancer, splenectomy
    • Risk: DVT, clotting

Coagulation Cascade (review)

• Goal → fibrin clot
• Extrinsic pathway (outside vessel)
  • Lab: \text{PT / INR}
  • Drug: Warfarin (vit K antagonist)
• Intrinsic pathway (endothelium injury)
  • Lab: \text{aPTT}
  • Drug: Heparin
• Pathways merge at Factor X → thrombin → fibrin

Inherited Bleeding Disorders

• Hemophilia A: Factor VIII deficiency (X-linked)
• Hemophilia B: Factor IX deficiency ("Christmas disease")
• von Willebrand Disease
  • Missing vWF protein → platelets can’t adhere
  • Autosomal dominant; heavy nosebleeds, menorrhagia, post-dental bleeding
  • Platelet problem vs. clotting-factor problem

Blood Typing & Transfusions

• ABO system
  • A, B, AB, O alleles (O lacks antigens → universal donor)
  • AB has both antigens → universal recipient
• Rh factor (+/–) – important in pregnancy & transfusion

Transfusion Reactions

1. Acute hemolytic (ABO incompatibility)
   • Immediate fever, flank pain, hypotension, hemoglobinuria, risk DIC
2. Febrile non-hemolytic – leukocyte reaction; treat with acetaminophen, antihistamine; usually continue transfusion
3. Allergic/minor – rash, itching
4. Fluid overload – esp. CHF; slow rate over ≤ 4 h
5. Infection/sepsis – improper storage (> 30 min unrefrigerated) → rapid fever, shock

Cardiac Electrical System & ECG Basics

• Conduction pathway & intrinsic rates

  1. SA node (60-100 bpm) – primary pacemaker
  2. AV node (40-60)
  3. Bundle of His (~40)
  4. Bundle branches
  5. Purkinje fibers (20-40)

• ECG wave meanings
  • P wave – atrial depolarization
  • PR segment – AV nodal delay
  • QRS – ventricular depolarization (systole)
  • ST segment – isoelectric; early repolarization
  • T wave – ventricular repolarization (diastole)

• Rhythms

  • Normal sinus rhythm: every P followed by QRS & T; rate determined by count ×10 on 6-s strip
  • Atrial fibrillation: irregularly irregular, no discernible P waves; atrial rate 300-350 bpm ➜ risk embolic stroke & clots; Tx rate-control + anticoagulation ± cardioversion

Hemodynamics

• Preload: ventricular stretch at end-diastole; ↓ with hemorrhage/volume loss
• Afterload: resistance LV must overcome to eject blood; ↑ with atherosclerosis & chronic HF
• Contractility: inherent strength; assessed via echocardiogram
• Cardiac Output (CO)
  CO = SV \times HR
  • Stroke Volume influenced by preload, afterload, contractility

Blood Pressure Regulation

• \text{BP} = CO \times \text{SVR} (systemic vascular resistance)
• Baroreceptors (carotid, aortic arch) & chemoreceptors (brain) give rapid feedback

Renin-Angiotensin-Aldosterone System (RAAS)

• Triggered by hypotension / low renal perfusion
• Sequence: kidney releases renin → converts angiotensinogen (liver) → angiotensin I → ACE (lungs) → angiotensin II → vasoconstriction + aldosterone (adrenals) → Na⁺/H₂O retention → ↑ BP
• Also activates coagulation in massive blood loss

Natriuretic Peptides (ANP & BNP)

• Triggered by cardiac overstretch / hypertension
• ANP (atria) & BNP (ventricles) → vasodilation + diuresis → ↓ blood volume & BP
• BNP also clinical biomarker for HF severity

Hypertension (HTN)

• “Silent killer” – often asymptomatic until organ damage
• Classification (adult)
  • Normal: <120/80
  • Elevated: 120-129/<80
  • Stage 1: 130-139/80-89
  • Stage 2: \ge 140/\ge 90
  • Crisis: >180/\text{and/or}>120
• Contributing pathophysiology
  • ↑ SVR (peripheral resistance)
  • ↑ Cardiac output
  • Hyperactive RAAS
• Chronic HTN complications
  • Heart: CAD, left-ventricular hypertrophy, HF, aortic aneurysm
  • Brain: stroke, encephalopathy
  • Eyes: retinopathy
  • Kidneys: CKD
  • Metabolic: insulin resistance ↑ blood sugar

Lipids & Atherosclerosis

• Lipid types
  • LDL (“bad”) – transports cholesterol to tissues; ↑ → atheroma
  • HDL (“good”) – returns cholesterol to liver for excretion
  • Triglycerides – circulating fats; ↑ with obesity, DM
• High LDL + high triglycerides ⇒ ↑ risk atherosclerosis

Coronary Atherosclerosis Development (4 steps)

1. Endothelial injury (HTN, smoking, diabetes, hyperlipidemia)
2. Fatty streak formation (lipid deposition)
3. Fibrous plaque (collagen cap, lumen narrows)
4. Complicated lesion – plaque ruptures → thrombus/emboli → ischemia/infarct

• Risk factors: modifiable (HTN, hyperlipids, diet, smoking), non-modifiable (age, male, family hx, ethnicity)
• Outcomes: CAD, MI, stroke, PAD, aneurysm

Peripheral & Venous Vascular Disorders

Peripheral Arterial Disease (PAD)

• Atherosclerosis in limb arteries
• Intermittent claudication: reproducible calf/leg pain on exertion relieved by rest (ischemia)
• Exam: pale/cool skin, weak/absent distal pulses, potential ischemic ulcers/gangrene

Venous Insufficiency & Varicosities

• Valve damage in leg veins ➜ blood reflux & stasis
• Risk: obesity, pregnancy, prolonged standing
• Venous ulcers: medial ankle/shin, shallow, exudative, necrotic tissue due to poor oxygenation

Raynaud’s Phenomenon

• Episodic arterial vasospasm in fingers/toes/nose/ears
• Pale, painful, clearly demarcated color change → then reperfusion redness
• Triggers: cold, stress, autoimmune diseases (e.g., Hashimoto’s)
• Not usually permanently ischemic but painful during attack

Quick Reference Summary

• Microcytic = iron-def or thalassemia; Macrocytic = B₁₂/folate; Normocytic = acute blood loss / ACD
• B₁₂ deficiency = neuro issues; Folate = no neuro
• Sickle cell = inherited HbS, painful crises; prevent hypoxia/infection
• Thrombocytopenia < 100 K – bleeding risk; Thrombocytosis > 750 K – clot risk
• Warfarin → PT/INR (extrinsic); Heparin → aPTT (intrinsic)
• Hemophilia A = VIII, B = IX; vWD = platelet adhesion protein missing
• RAAS saves BP in shock; ANP/BNP protect heart in fluid overload
• HTN untreated damages heart, brain, eyes, kidneys – check BP routinely!