PATH FINAL From review stuff

Atrophy

↓ cell SIZE — cells shrink due to decreased workload, ischemia, denervation, or loss of hormonal stimulation

Hypertrophy

↑ cell SIZE — cells grow larger in response to increased workload; common in non-dividing cells (e.g., cardiac muscle)

Hyperplasia

↑ cell NUMBER — occurs in cells capable of division; driven by growth factor signaling

Metaplasia

REVERSIBLE switch from one differentiated cell type to another; can progress to dysplasia if stimulus persists

Dysplasia

DISORDERED GROWTH — abnormal cell size, shape, and organization; NOT a normal adaptive response; pre-malignant

Hyperplasia vs. Hypertrophy

Hyperplasia = ↑ number (mitosis);
Hypertrophy = ↑ size (no new cells); can occur together (e.g., pregnant uterus)

Endometrial Hyperplasia

Caused by ↑ unopposed estrogen (e.g., anovulatory cycles); excess estrogen drives endometrial cell proliferation

BPH (Benign Prostatic Hyperplasia)

Driven by DHT (dihydrotestosterone); does NOT progress to prostate cancer

Barrett's Esophagus

Chronic acid reflux:
normal stratified squamous epithelium → non-ciliated columnar epithelium; ↑ risk of adenocarcinoma

Smoker's Metaplasia

Normal respiratory pseudostratified ciliated columnar →
stratified squamous epithelium;
caused by chronic irritation

Cervical Intraepithelial Neoplasia (CIN)

Classic dysplasia; caused by HPV 16 & 18; disordered/pre-malignant growth — NOT a normal adaptive response

Reversible Injury — ATP Depletion

Mild to moderate;
Na/K-ATPase fails → intracellular Na+ ↑ → water influx →
cell swelling (hydropic change)

Irreversible Injury — ATP Depletion

Severe and prolonged; ion pump failure becomes irreversible → membrane rupture → cell death

Reversible Injury — Cell Membrane

Integrity maintained; plasma membrane intact (blebs may form but no rupture)

Irreversible Injury — Cell Membrane

LOST — plasma membrane ruptures → contents leak → triggers inflammation

Reversible Injury — Mitochondria

Swelling only; outer membrane intact; cytochrome c NOT released

Irreversible Injury — Mitochondria

Severe damage + membrane rupture; cytochrome c released → triggers apoptosis cascade; large flocculent densities form

Reversible Injury — Nuclear Changes

No significant change to nucleus

Irreversible Injury — Nuclear Changes

3 patterns:
1. pyknosis: condensed/dark

2. karyorrhexis: fragmented

3. karyolysis: dissolved

Pyknosis

Nuclear shrinkage and increased basophilia (dark, shrunken nucleus);
first nuclear sign of irreversible injury

Karyorrhexis

Nuclear fragmentation — chromatin breaks into scattered pieces; seen in irreversible injury/necrosis

Karyolysis

Nuclear dissolution/fading — DNA digested by DNases; seen in late necrosis

Reversible Injury — Fatty Change

Seen especially in liver; reversible if insult removed before membrane rupture

Reversible Injury — Outcome

Full recovery possible if insult removed in time

Irreversible Injury — Outcome

Cell death — either necrosis or apoptosis depending on mechanism

Reversible Injury — ER

ER swelling; dispersion of ribosomes → ↓ protein synthesis

Reversible Injury — Lysosomes

Autophagy by lysosomes (recycling damaged organelles); no rupture yet

Irreversible Injury — Lysosomes

Rupture of lysosomes → autolysis (lysosomal enzymes digest cell from within)

Irreversible Injury — ER

Complete lysis of ER

Myelin Figure

Whorls of phospholipids from damaged cell membranes; seen in both reversible injury and early necrosis

Necrosis — Cause

Always PATHOLOGICAL; caused by external insult (ischemia, toxins, infection)

Apoptosis — Cause

May be PHYSIOLOGICAL (embryogenesis, immune deletion) OR pathological (DNA damage, viral infection)

Necrosis — Scope

Affects adjacent GROUPS of cells simultaneously

Apoptosis — Scope

Affects SINGLE cells; scattered pattern

Necrosis — Cell Size

INCREASED — cell swells due to ion pump failure and water influx

Apoptosis — Cell Size

SHRUNKEN — cytoplasm and nucleus condense

Necrosis — Process

PASSIVE — uncontrolled, energy-independent

Apoptosis — Process

ACTIVE — energy-dependent; requires ATP; executed by caspases

Necrosis — Inflammation

CAUSES inflammatory reaction — DAMPs released from ruptured membrane trigger innate immunity

Apoptosis — Inflammation

NO inflammatory reaction — apoptotic bodies cleanly phagocytosed; membrane stays intact

Necrosis — Plasma Membrane

DISRUPTED — membrane ruptures and contents spill

Apoptosis — Plasma Membrane

INTACT — blebs form but membrane stays sealed; contents packaged into apoptotic bodies

Apoptosis — Key Steps

Chromatin condensation → membrane blebbing → cellular fragmentation → apoptotic bodies → phagocytosis by macrophages

Coagulative Necrosis

Architecture PRESERVED (ghost outlines of dead cells); caused by ischemia to all solid organs EXCEPT CNS; also thermal injury

Zenker's Degeneration

Coagulative necrosis of the rectus abdominis muscle; seen in severe systemic infections (e.g., typhoid fever)

Liquefactive Necrosis

Tissue completely digested → liquid/pus; caused by ischemia to the BRAIN or bacterial infections (wet gangrene)

Liquefactive Necrosis — Brain Exception

Brain undergoes liquefactive (not coagulative) necrosis due to high lipid content and abundant hydrolytic enzymes

Caseous Necrosis

"Cheese-like" gross appearance; combo of coagulative + liquefactive; surrounded by granuloma; seen in TB, syphilis, histoplasmosis

Caseous Necrosis — Organisms

TB (Mycobacterium tuberculosis), Syphilis (Treponema pallidum), Histoplasma capsulatum

Fat Necrosis — Traumatic

Direct trauma to fat-containing tissue (breast, buttock, abdomen) → fat cell destruction

Fat Necrosis — Enzymatic

Pancreatitis → pancreatic lipases released → fatty acids + Ca²⁺ → calcium soaps (saponification); chalky-white deposits grossly

Fibrinoid Necrosis

Seen in VESSEL WALLS only; fibrin-like material deposited in walls; causes: vasculitis, malignant hypertension, immune complex deposition

Coagulative vs. Liquefactive

Coagulative = architecture preserved, solid organs (not CNS);
Liquefactive = architecture destroyed, brain + bacterial infections

Caseous vs. Coagulative

Caseous = no architecture + "cheesy" + granuloma; Coagulative = ghost cells preserved, no granuloma

Transudate — Protein Content

Low (<2.5-3.0 g/dL); ultrafiltrate with little protein

Exudate — Protein Content

High (>2.5-3.0 g/dL); protein-rich due to ↑ vascular permeability

Transudate — Specific Gravity

<1.012

Exudate — Specific Gravity

>1.020

Transudate — LDH

Low

Exudate — LDH

High

Transudate — Appearance

Clear and watery

Exudate — Appearance

Cloudy/turbid; may be yellow or purulent

Transudate — Cellularity

Few cells; mostly mononuclear

Exudate — Cellularity

Many cells; neutrophils and macrophages predominate

Transudate — Mechanism

↑ Hydrostatic pressure OR ↓ oncotic pressure; no inflammation involved

Exudate — Mechanism

↑ Vascular permeability from inflammation → proteins and cells leak out

Transudate — Common Causes

CHF, nephrotic syndrome, liver cirrhosis

Exudate — Common Causes

Infection (e.g., pneumonia), inflammation, malignancy

Edema — Increased Hydrostatic Pressure

Impaired venous return: CHF, constrictive pericarditis, cirrhosis, venous thrombosis, external compression

Edema — Arteriolar Dilation

Heat or neurohumoral dysregulation → ↑ capillary pressure → fluid leaks out

Edema — Reduced Plasma Osmotic Pressure

Hypoproteinemia: nephrotic syndrome, liver cirrhosis, malnutrition, protein-losing gastroenteropathy

Edema — Lymphatic Obstruction

Blocked lymph drainage: inflammatory, neoplastic, postsurgical, or postirradiation causes

Edema — Sodium Retention

Excessive salt intake with renal insufficiency OR ↑ tubular reabsorption via RAAS activation

Edema — Inflammation

Acute/chronic inflammation → ↑ vascular permeability → fluid accumulates in tissue

Leukocyte Extravasation — Step 1: Margination & Rolling

Selectins (E-selectin, P-selectin on endothelium) bind sialyl-Lewis X on leukocytes; loose, reversible adhesion

Leukocyte Extravasation — Step 2: Adhesion

Integrins (CD18/LFA-1, Mac-1) on leukocytes bind ICAM-1/VCAM-1 on endothelium; firm, irreversible binding

Leukocyte Extravasation — Step 3: Diapedesis

Leukocytes squeeze through endothelium via PECAM-1 (CD31) at postcapillary venules

Leukocyte Extravasation — Step 4: Chemotaxis

Migration toward injury guided by C5a, IL-8, LTB4, and bacterial products

Selectins — Role

E-selectin and P-selectin on endothelium mediate rolling; rapidly expressed after TNF/IL-1 stimulation

Integrins — Role

CD18/LFA-1 and Mac-1 bind ICAM/VCAM; mediate firm adhesion (upregulated by TNF, IL-1)

PECAM-1 (CD31)

Mediates diapedesis — leukocytes transmigrate through interendothelial junctions at postcapillary venules

Chemotaxis — Key Mediators

C5a, IL-8 (CXCL8), LTB4, and bacterial products (e.g., fMLP)

Rubor (Redness)

Vasodilation → ↑ blood flow; mediators: Histamine, PGE₂, PGI₂, NO

Calor (Heat)

Vasodilation + ↑ blood flow → local temperature rise; mediators: Histamine, Prostaglandins, NO

Tumor (Swelling)

↑ Vascular permeability → exudate into tissue; mediators: Histamine, Bradykinin, LTC₄, LTD₄

Dolor (Pain)

Direct nerve stimulation; mediators: Bradykinin, PGE₂, IL-1, TNF-α

Functio Laesa (Loss of Function)

Combination of pain, swelling, and tissue damage; indirect result of all inflammatory mediators

Arachidonic Acid — Source

Released from cell membrane phospholipids by phospholipases; blocked upstream by corticosteroids

Arachidonic Acid — COX Pathway

Cyclooxygenase → PGG₂ → PGH₂ → PGI₂, TXA₂, PGD₂, PGE₂; blocked by aspirin/NSAIDs

Arachidonic Acid — 5-LOX Pathway

5-Lipoxygenase →
LTB4 (chemotaxis)
LTC₄, LTD₄, LTE₄ (bronchoconstriction, ↑ permeability)

Prostacyclin (PGI₂)

Vasodilation + inhibits platelet aggregation; produced by endothelium

Thromboxane A₂ (TXA₂)

Vasoconstriction + promotes platelet aggregation; produced by platelets

PGD₂ / PGE₂

Vasodilation, ↑ vascular permeability, leukocyte chemotaxis

LTB4

Potent neutrophil chemotactic agent; via 5-lipoxygenase pathway

LTC₄, LTD₄, LTE₄

Cysteinyl leukotrienes → bronchospasm + ↑ vascular permeability; blocked by montelukast

Lipoxins (LXA₄, LXB₄)

Via 12-lipoxygenase;
1. inhibit neutrophil adhesion

2. chemotaxis — pro-resolution mediators

Steroids — Mechanism

Inhibit phospholipases → block arachidonic acid release →
suppress both COX and LOX pathways

NSAIDs/Aspirin — Mechanism

Inhibit COX-1 and COX-2 → block prostaglandin/thromboxane synthesis;
do NOT block leukotriene pathway

Acute Inflammation — Key Features

Vascular changes, neutrophil recruitment, mediator release; caused by infarction, infection, toxins, trauma

Acute Inflammation — Resolution

Clearance of stimulus + mediators + inflammatory cells → injured cells replaced → normal function restored