Pathophysiology – Midterm Comprehensive Bullet Notes (Summer 2025)

Cellular Processes & Wound Physiology

• Apoptosis (Programmed Cell Death)
– Genetically regulated sequence that removes damaged / unnecessary cells.
– Failure ➜ uncontrolled proliferation (neoplasia, cancer).
– Physiologic roles: embryologic sculpting, immune cell deletion, tumor-suppression safeguards.

• Eschar
– Thick, black/brown, avascular necrotic tissue.
– Blocks epithelial migration & granulation ➜ must be removed.
– Removal = Debridement (surgical, mechanical, chemical, autolytic).

• Acute Inflammation – 3 Classic Vascular Phases

Vasodilation – arteriolar smooth-muscle relaxation → ↑ local blood flow (rubor, calor).
↑ Vascular Permeability – endothelial contraction, histamine → plasma proteins/leukocytes exit circulation (tumor).
Cellular Exudation – neutrophils follow chemotactic gradients to the site.

• Wound Dehiscence
– Partial/complete separation of approximated wound edges.
– Risk factors: infection, tension, malnutrition, obesity, steroid therapy, diabetes.
– Can precipitate evisceration, secondary infection; urgent surgical review required.

• Healing by Secondary Intention
– For wide tissue gaps, infected or unsuturable wounds.
– Features: prolonged repair time, ↑ infection risk, larger/scars.
– Granulation tissue must fill defect → myofibroblast-mediated contraction.

• Four Stages of Cutaneous Repair

Hemostasis – immediate vasoconstriction & platelet plug → fibrin clot.
Inflammation – neutrophils ⇒ macrophages cleanse debris/pathogens.
Proliferation – fibroblast collagen type III, angiogenesis, epithelial resurfacing.
Contraction & Remodeling – conversion to collagen I, tensile strength ↑ to ≈ $80\%$ of normal after $>1$ yr.

• Signs vs. Symptoms
– Sign (objective): rash, fever, murmur.
– Symptom (subjective): pain, fatigue, pruritus.

Infection & Immunology

• Clostridium tetani
– Obligate anaerobe; tetanospasmin blocks inhibitory neurotransmitters (GABA, glycine) ➜ rigid paralysis, “lock-jaw.”

• Clostridium botulinum
– Botulinum toxin cleaves SNARE-proteins → blocks acetylcholine release → flaccid paralysis, dysphagia, respiratory failure.
– Therapeutic micro-doses used for migraines, dystonias, cosmetic Botox.

• Staphylococcus aureus Resistance
– MRSA: resistant to methicillin/β-lactams.
– VRSA: additionally resistant to vancomycin (last-line glycopeptide).
– Acquisition: hospital (HA-MRSA) or community (CA-MRSA).

• Epstein–Barr Virus (EBV) & Infectious Mononucleosis
– Salivary transmission (“kissing disease”).
– Remains latent in B cells; can reactivate.
– Association with Hodgkin lymphoma, Burkitt lymphoma, nasopharyngeal carcinoma.

• Hypersensitivity Types
– Type I (Immediate, IgE): anaphylaxis, atopy.
– Type II (Cytotoxic, IgG/IgM to cell surface): hemolytic transfusion reaction.
– Type III (Immune-complex): SLE, rheumatoid arthritis.
– Type IV (Delayed, T-cell): poison ivy, TB skin test.

• Mast Cells
– Sentinels in connective tissue; FcεRI receptors for IgE.
– Degranulate histamine, tryptase → vasodilation, bronchoconstriction (allergy, anaphylaxis).

• Arteriovenous (AV) Fistula for Hemodialysis
– Surgically anastomose artery ↔ vein (usually radial artery → cephalic vein).
– Maturation $6–12$ wk; offers high blood-flow, low infection vs. graft/catheter.

• Selective IgA Deficiency
– Most common primary immunodeficiency; recurrent sinopulmonary and GI infections; often asymptomatic.

Hematology

• Anemia – Key Etiologies
– Iron Deficiency: diet, chronic blood loss.
– Chronic Disease: inflammation-mediated iron sequestration.
– Folate/B $12$ Deficiency: megaloblastic anemia (macrocytosis, hyper-segmented neutrophils).
– Sickle Cell Disease: point mutation β-globin (Glu➜Val) → HbS polymerization under hypoxia.

➔ Genetics: autosomal recessive; two carrier parents → $25\%$ affected, $50\%$ carriers, $25\%$ normal.

• Iron-Deficiency Management

Oral ferrous sulfate $(325\,mg)$ TID with $\mathrm{Vit\,C}$ to improve absorption.
IV iron (e.g., ferric carboxymaltose) if malabsorption, intolerance, or severe deficit.
– Side-effect: constipation, black stools.

• Hemorrhage
– Acute loss of $>30\%$ circulating volume → hypovolemic shock: hypotension, tachycardia, oliguria, ↓ hematocrit.

• Hemophilia
– X-linked recessive; deficiency of Factor VIII (Hem A) or IX (Hem B).
– Treat: recombinant clotting factor concentrates; avoid NSAIDs/IM injections.

• Erythroblastosis Fetalis (Hemolytic Disease of Newborn)
– Rh− mother sensitised to Rh+ fetal blood → IgG crosses placenta, hemolysis → jaundice, hydrops.
– Prevention: anti-D IgG at $28$ wk & postpartum.

• Immune Thrombocytopenic Purpura (ITP)
– Autoantibodies vs. platelet GPIIb/IIIa after viral illness; petechiae, bruising.
– Tx: steroids, IVIG; often self-limited in children.

• Chronic Lymphocytic Leukemia (CLL)
– Clonal mature-appearing but immunologically immature B cells accumulate; common > $55$ y.
– Smudge cells on smear; can progress to Richter’s transformation.

• Hodgkin Lymphoma
– Reed-Sternberg (bilobed, CD $15$ +/CD $30$ +) cells; bimodal age distribution; EBV association.

Thrombosis & Vascular Pathology

• Virchow’s Triad for Thrombosis

Venous Stasis – immobility, postoperative bed rest.
Hypercoagulability – cancer, Factor V Leiden, pregnancy.
Endothelial Injury – surgery, trauma, indwelling catheters.

• Deep-Vein Thrombosis (DVT)
– Calf pain, unilateral swelling; risk of pulmonary embolism.

• Varicose Veins / Varicosities
– Valve incompetence → venous pooling, dilatation esp. in legs; aggravated by pregnancy, obesity.

Neurologic & Genetic Disorders

• Huntington’s Disease
– Autosomal dominant, $\mathrm{CAG}$ repeat expansion on chromosome $4$ (anticipation).
– Progressive chorea, psychiatric decline, dementia; caudate atrophy on imaging.

Autoimmune Disorders

• Systemic Lupus Erythematosus (SLE)
– Type III hypersensitivity; immune-complex deposition in skin/kidney/joints → fever, arthralgia, malar “butterfly” rash.

Respiratory Pathophysiology

• Pneumothorax
– Air in pleural space → lung collapse.
– Auscultation: absent breath sounds over affected side.
– Tension variant: mediastinal shift, hemodynamic compromise.

• Pleural Effusion
– Excess fluid; mechanisms: ↑ hydrostatic pressure (CHF) or ↓ oncotic (hypo-albuminemia).
– Thoracentesis diagnostic/therapeutic.

• Pneumonia
– Infection of alveoli; CAP most commonly Streptococcus pneumoniae.
– Presentation: cough, fever, crackles; vaccinated with PPSV $23$ or PCV $13$ .

• Asthma
– Reversible bronchial hyper-reactivity; wheeze, nocturnal cough; spirometry shows ↓ FEV $1$ , improved with bronchodilator.

• Chronic Obstructive Pulmonary Disease (COPD) – Emphysema
– Centriacinar (smokers) vs panacinar (α $1$ -antitrypsin deficiency).
– ↓ elastic recoil → air trapping, barrel chest.

• Acute Bronchitis
– Viral > $90\%$ ; productive cough ± low-grade fever; yellow sputum ≠ bacterial necessarily.
– Tx: hydration, expectorant (guaifenesin); reserve antibiotics for proven bacterial infection.

Cardiovascular Pathophysiology

• Heart Disease Risk Factors
– Non-modifiable: age, genetics.
– Modifiable: diet, sedentary lifestyle, smoking, hyper-lipidemia.
– Regular moderate exercise ↓ CVD risk by ≈ $30\%$ .

• Cardiac Dysrhythmias
– Bradycardia (< $60$ bpm), Tachycardia (> $100$ bpm), Atrial Fibrillation (irregularly irregular), Ventricular Fibrillation (pulseless).

• Angina Pectoris
– Stable: exertional, relieved by rest/SL nitroglycerin.
– Unstable: unpredictable, at rest; precursor to MI.
– Variant (Prinzmetal): coronary spasm; transient ST-elevation.

• Nitroglycerin Mechanism
– Converts to $NO$ → ↑ cGMP → venodilation (↓ preload) & coronary vasodilation.

• Myocardial Infarction (MI)
– Ruptured atherosclerotic plaque → thrombotic occlusion.
– Symptoms: crushing chest pain, diaphoresis, dyspnea, Levine sign; women: atypical (fatigue, epigastric pain).
– Biomarker: Cardiac Troponin I/T rises within $3–4$ h, peaks $24$ h.
– Complications: arrhythmias, heart failure, ventricular rupture.

• Coronary Artery Bypass Grafting (CABG)
– Uses internal mammary artery or saphenous vein; multiple grafts possible; indicated for multi-vessel disease/uncontrolled angina.

• Heart Failure
– Left-Sided (LVF): pulmonary congestion → crackles, orthopnea, paroxysmal nocturnal dyspnea.
– Right-Sided (RVF): systemic venous congestion → JVD, ascites, peripheral edema, hepatomegaly; often secondary to LVF or pulmonary disease.

• Orthopnea
– Dyspnea supine; relieved upright; reflects redistribution of fluid to lungs when recumbent.

• Cor Pulmonale
– Right-sided failure from chronic pulmonary hypertension (e.g., COPD, interstitial lung).
– Management: treat underlying lung disease, oxygen, diuretics.

• Hypertrophic Cardiomyopathy (HCM)
– AD mutations in β-myosin heavy chain; asymmetric septal hypertrophy → LVOT obstruction; risk of sudden death in athletes; maneuvers ↓ preload (e.g., Valsalva) exacerbate murmur.

• Infective Endocarditis
– Bacteremia seeds damaged/abnormal valves; risk: IV drugs (tricuspid), dental work; presents with fever, new murmur, Janeway lesions.

• Exercise Stress Test
– Incremental treadmill/cycle while monitoring ECG, BP; unmask ischemia not evident at rest (ST depression, angina).
– Contraindications: acute MI, severe AS, uncontrolled arrhythmias.