BP104T Unit 5 – Cardiovascular System & Hemodynamics
Unit 5 details the cellular and molecular mechanisms of cell injury (hypoxia, ischemia, ROS, free radical pathology), reversible cellular swelling vs irreversible necrosis vs apoptosis, vascular and cellular events of acute inflammation, chemical inflammatory mediators, and tissue repair by primary and secondary intention.
📋 Prescribed Syllabus Topics
📖 Detailed Lecture Notes & Solved Examples
11. Etiology & Mechanisms of Reversible vs. Irreversible Cell Injury
Dedicated Webpage➔Cell injury occurs when environmental stresses exceed the adaptive capacity of the cell. The primary etiologies include Hypoxia (oxygen deprivation), Ischemia (loss of arterial blood supply), Reactive Oxygen Species (ROS / Free radicals), physical trauma, chemical toxins, and genetic defects. The critical biochemical point of no return distinguishing Reversible Injury from Irreversible Injury (cell death) is characterized by severe mitochondrial dysfunction with inability to regenerate ATP and massive breakdown of plasma membrane permeability allowing catastrophic influx of extracellular calcium ($Ca^{2+}$).Jab cell ko oxygen nahi milti (Ischemia), toh mitochondria ATP banana band kar deta hai. ATP na hone se Na+/K+ pump ruk jata hai aur cell me paani bhar jata hai jisse wo sooj jati hai (Hydropic change). Agar nuksan badhta hai toh bahar se Calcium (Ca2+) andar ghuskar cell ke DNA aur membrane ko tod deta hai jisse Irreversible cell death ho jati hai.
▶Sequential Biochemical Cascade in Ischemic Cell Injury
From arterial occlusion to irreversible membrane rupture.
- •Reversible Injury Hallmark: Cellular swelling (hydropic change) and fatty change (steatosis).
- •Irreversible Injury Hallmark: Inability to restore mitochondrial function + Severe structural membrane disruption + Massive Ca2+ influx.
- •Nuclear Changes in Necrosis: Pyknosis (nuclear shrinkage and condensation) $\rightarrow$ Karyorrhexis (nuclear fragmentation) $\rightarrow$ Karyolysis (nuclear dissolution by DNases).
22. Types of Necrosis vs. Apoptosis (Programmed Cell Death)
Dedicated Webpage➔Cell death occurs primarily through two distinct pathways: Necrosis (accidental, uncontrolled pathological cell death accompanied by cellular swelling, membrane rupture, enzymatic digestion, and vigorous surrounding inflammation) and Apoptosis (programmed, gene-directed physiological cell suicide requiring ATP, characterized by cell shrinkage, chromatin condensation, apoptotic body formation, and zero surrounding inflammation).Necrosis achanak hone wali aniyantrit (uncontrolled) cell death hai jisme cell phat jati hai aur aaspas tez sujan/peep banati hai (Coagulative necrosis heart attack me, Caseous TB me). Apoptosis ek shant, planned cell suicide hai jisme koi sujan nahi hoti aur Caspase enzymes purane cells ko saaf karte hain.
▶Classification and Morphological Patterns of Tissue Necrosis
Five major pathological types of necrosis.
| Feature | Necrosis (Pathological Lysis) | Apoptosis (Programmed Suicide) |
|---|---|---|
| Etiology | Always pathological (severe ischemia, toxins, trauma) | Physiological (embryogenesis) or pathological (DNA damage) |
| Cellular Volume | Cellular swelling (hydropic enlargement) and lysis | Cellular shrinkage and fragmentation into apoptotic bodies |
| Membrane Integrity | Ruptured, fragmented (leakage of intracellular enzymes) | Intact (surface altered with Phosphatidylserine for phagocytosis) |
| Inflammatory Response | Vigorous, severe surrounding inflammation | Zero inflammation (neat phagocytic clearance) |
| Mechanism | ATP depletion, membrane calcium influx | Energy-dependent (ATP required), Caspase enzyme cascade |
- •Apoptosis: Programmed, physiological or pathological, caspase-dependent, no inflammatory reaction.
- •Intrinsic Apoptotic Pathway: Mitochondrial stress -> Bax/Bak activation -> Cytochrome C release -> Apaf-1 apoptosome -> Cleaves Procaspase-9 -> Activates executioner Caspases-3 and 7.
- •Extrinsic Apoptotic Pathway: FasL or TNF-alpha binds death receptors (Fas/CD95, TNFR1) -> FADD -> Activates Caspase-8 -> Activates executioner Caspases.
33. Acute Inflammation: Vascular & Cellular Events and Chemical Mediators
Dedicated Webpage➔Acute Inflammation is the immediate, protective homeostatic response of vascularized living tissue to infection, physical trauma, or tissue necrosis. The five cardinal clinical signs of inflammation (Celsus and Virchow) are: Rubor (redness), Calor (heat), Tumor (swelling), Dolor (pain), and Functio Laesa (loss of function). The process consists of coordinated Vascular Events (transient arteriolar vasoconstriction followed by persistent vasodilation, increased microvascular permeability, and exudate formation) and Cellular Events (Neutrophil Margination, Rolling, Stable Adhesion, Diapedesis/Emigration, Chemotaxis, and Phagocytosis).Sujan (Inflammation) ke 5 lakshan hote hain: Rubor (laal hona), Calor (garam hona), Tumor (soojna), Dolor (dard), aur Functio laesa (ang ka kaam na karna). Blood vessels se Neutrophils nikalte hain (Rolling -> Adhesion -> Diapedesis) aur bacteria ko kha jate hain. Aspirin aur Ibuprofen Prostaglandins ko rok kar dard aur sujan kam karti hain.
▶Cellular Leukocyte Extravasation & Phagocytosis Cascade
Step-by-step neutrophil recruitment to the infection site.
- •Vascular Permeability Mediators: Histamine and Serotonin cause immediate transient endothelial contraction (gaps); Bradykinin, Leukotrienes (LTC4, LTD4, LTE4).
- •Pain (Dolor) Mediators: Bradykinin and Prostaglandin E2 (PGE2) sensitize nociceptors.
- •Fever (Pyrexia) Mediators: IL-1, TNF-alpha, and IL-6 stimulate hypothalamic synthesis of PGE2.
- •Anti-Inflammatory Drug Targets: NSAIDs (Aspirin, Ibuprofen) inhibit Cyclooxygenase (COX-1/COX-2), blocking Prostaglandin synthesis; Corticosteroids inhibit Phospholipase A2 via Lipocortin/Annexin A1.
44. Tissue Repair, Regeneration & Wound Healing (Primary vs. Secondary Intention)
Dedicated Webpage➔Tissue repair is the restoration of tissue architecture and function following injury. It occurs through two distinct processes: Regeneration (proliferation of undamaged uninjured parenchymal cells restoring native tissue architecture, seen in labile and stable cells) and Scar Formation / Fibrosis (replacement of non-regenerated parenchymal cells with collagenous connective tissue when underlying structural extracellular framework is destroyed). Wound healing progresses through four overlapping phases: (1) Hemostasis (fibrin clot), (2) Inflammation (macrophage debris clearance), (3) Proliferation (Granulation tissue formation, angiogenesis, fibroblast collagen deposition, epithelialization), and (4) Remodeling / Maturation (Type III collagen replaced by dense Type I collagen).Ghav bharne ke 2 tarike hote hain: Primary Intention (clean surgical cut jisme taanke lagte hain aur bina nishaan ke ghav jaldi bhar jata hai) aur Secondary Intention (bade khule ghav jisme pehle laal Granulation tissue banta hai aur Myofibroblasts ghav ko kheench kar chhota karte hain, isme bada nishaan banta hai).
▶Healing by Primary Intention vs. Secondary Intention
Contrasting clinical wound types.
| Characteristic | Primary Intention (First Intention) | Secondary Intention |
|---|---|---|
| Wound Edges | Clean, opposed closely by sutures or staples | Widely separated, gaping, ragged margins |
| Tissue Loss | Minimal loss of parenchymal tissue | Extensive tissue and basement membrane loss |
| Granulation Tissue | Small, narrow amount formed | Abundant, exuberant granulation tissue required |
| Wound Contraction | Virtually absent | Prominent (myofibroblasts pull wound margins together) |
| Scar Formation | Thin, linear, cosmetically minimal scar | Large, broad, irregular, fibrotic scar / keloid potential |
| Infection Risk | Very low under aseptic surgical conditions | High risk of bacterial contamination and necrosis |
- •Granulation Tissue: Specialized vascular tissue appearing pink, soft, and granular; composed of newly formed budding capillaries (Angiogenesis / Neovascularization driven by VEGF) and active proliferating Fibroblasts (driven by TGF-beta and bFGF).
- •Myofibroblasts: Modified fibroblasts containing smooth muscle alpha-actin that contract, reducing wound surface area by up to 80% during secondary intention.
- •Wound Strength: Approx. 10% of unwounded skin strength at 1 week (when sutures removed); plateaus at 70-80% of original tensile strength at 3 months.
- In a 10-mark question on Acute Inflammation, describe all vascular and cellular events and draw the diagram of leukocyte rolling, adhesion, diapedesis, and chemotaxis.
- Contrast Healing by Primary Intention vs Healing by Secondary Intention in a neat comparative table.