WGU D236 Pathophysiology Competency Mastery
Guide - 2026/2027 Edition | Complete Exam Review
System | Disease Mechanism Mastery
Unit 1: Cellular & Systemic Foundations
Competency: Explain the cellular injury–inflammation cascade, fluid–electrolyte shifts,
acid-base disturbances, and genetic influence on disease risk.
1.1 Cellular Injury & Inflammation
Part A – Competency & Key Concepts
● Objective: Describe how reversible vs. irreversible cellular injury triggers the
inflammatory cascade.
● Key mechanisms:
○ ATP depletion → Na⁺/K⁺ pump failure → cellular swelling
○ Membrane phospholipid breakdown → release of prostaglandins &
leukotrienes
○ Cytokine (IL-1, TNF-α) activation of endothelial adhesion molecules →
margination & diapedesis
Part B – Deep-Dive Mechanism
When oxidative phosphorylation fails (hypoxia, toxins), intracellular ATP drops within
minutes. The Na⁺/K⁺ ATPase stalls, Na⁺ accumulates, water follows osmotically, and
the cell swells (hydropic change). Simultaneously, Ca²⁺ leaks into the cytosol, activating
phospholipases and proteases that digest membrane proteins and phospholipids. Once
,the plasma membrane is breached, intracellular enzymes (e.g., troponin, CK-MB) spill
into plasma, providing clinical biomarkers. Inflammatory cells are recruited by IL-8 and
complement fragment C5a; neutrophils roll, adhere, and migrate toward the injured
tissue, amplifying the inflammatory response.
Part C – Clinical Application
Scenario: A 56-year-old man presents with crushing chest pain; troponin I is 12 ng/mL
(high).
Q: Why does the elevated troponin confirm irreversible myocardial injury?
Answer: Troponin is bound to the actin-myosin complex inside cardiac myocytes; its
presence in plasma indicates sarcolemmal disruption—an irreversible step.
Part D – Competency Assessment
1. Which lab value best distinguishes reversible from irreversible cellular injury?
A. Elevated serum lactate
B. Elevated serum troponin I
C. Elevated C-reactive protein
D. Elevated serum glucose
Answer: B
Rationale: Troponin is an intracellular structural protein; extracellular detection
implies membrane rupture—irreversible injury.
2. Select all that apply. Inflammatory cell margination is mediated by:
A. Selectins on endothelium
B. Integrins on neutrophils
C. IL-1–induced ICAM-1 up-regulation
D. Histamine-induced vasoconstriction
Answer: A, B, C
Rationale: Margination requires selectin-mediated rolling (A), integrin-mediated
adhesion (B), and cytokine-up-regulated adhesion molecules (C). Histamine
causes vasodilation, not constriction (D incorrect).
, 1.2 Fluid & Electrolyte Shifts
Part A – Competency & Key Concepts
● Objective: Predict edema or dehydration based on Starling forces and ADH/RAAS
responses.
● Key mechanisms:
○ ↓Plasma oncotic pressure (nephrotic syndrome, liver failure) → peripheral
edema
○ ↑ADH (SIADH) → water retention → dilutional hyponatremia
○ Aldosterone escape vs. aldosterone breakthrough
Part B – Deep-Dive Mechanism
In nephrotic syndrome, massive albuminuria drops serum albumin below ~2 g/dL. The
reduced intravascular oncotic pressure no longer counterbalances hydrostatic pressure,
so fluid filters into interstitial spaces, producing periorbital and pedal edema. Despite
falling plasma volume, ADH and aldosterone are activated, causing renal sodium and
water retention. However, because the primary defect is low oncotic pressure, the
retained fluid simply leaks into the interstitium, worsening edema.
Part C – Clinical Application
Scenario: A 7-year-old boy with nephrotic syndrome has 3+ pitting edema and serum
Na⁺ 128 mEq/L.
Q: Why is hyponatremia dilutional rather than depletional?
Answer: ADH-driven water retention exceeds sodium retention, expanding total body
water and lowering serum Na⁺ despite normal total body sodium.
Part D – Competency Assessment
1. Which finding best supports that edema is due to decreased plasma oncotic
pressure rather than increased hydrostatic pressure?
Guide - 2026/2027 Edition | Complete Exam Review
System | Disease Mechanism Mastery
Unit 1: Cellular & Systemic Foundations
Competency: Explain the cellular injury–inflammation cascade, fluid–electrolyte shifts,
acid-base disturbances, and genetic influence on disease risk.
1.1 Cellular Injury & Inflammation
Part A – Competency & Key Concepts
● Objective: Describe how reversible vs. irreversible cellular injury triggers the
inflammatory cascade.
● Key mechanisms:
○ ATP depletion → Na⁺/K⁺ pump failure → cellular swelling
○ Membrane phospholipid breakdown → release of prostaglandins &
leukotrienes
○ Cytokine (IL-1, TNF-α) activation of endothelial adhesion molecules →
margination & diapedesis
Part B – Deep-Dive Mechanism
When oxidative phosphorylation fails (hypoxia, toxins), intracellular ATP drops within
minutes. The Na⁺/K⁺ ATPase stalls, Na⁺ accumulates, water follows osmotically, and
the cell swells (hydropic change). Simultaneously, Ca²⁺ leaks into the cytosol, activating
phospholipases and proteases that digest membrane proteins and phospholipids. Once
,the plasma membrane is breached, intracellular enzymes (e.g., troponin, CK-MB) spill
into plasma, providing clinical biomarkers. Inflammatory cells are recruited by IL-8 and
complement fragment C5a; neutrophils roll, adhere, and migrate toward the injured
tissue, amplifying the inflammatory response.
Part C – Clinical Application
Scenario: A 56-year-old man presents with crushing chest pain; troponin I is 12 ng/mL
(high).
Q: Why does the elevated troponin confirm irreversible myocardial injury?
Answer: Troponin is bound to the actin-myosin complex inside cardiac myocytes; its
presence in plasma indicates sarcolemmal disruption—an irreversible step.
Part D – Competency Assessment
1. Which lab value best distinguishes reversible from irreversible cellular injury?
A. Elevated serum lactate
B. Elevated serum troponin I
C. Elevated C-reactive protein
D. Elevated serum glucose
Answer: B
Rationale: Troponin is an intracellular structural protein; extracellular detection
implies membrane rupture—irreversible injury.
2. Select all that apply. Inflammatory cell margination is mediated by:
A. Selectins on endothelium
B. Integrins on neutrophils
C. IL-1–induced ICAM-1 up-regulation
D. Histamine-induced vasoconstriction
Answer: A, B, C
Rationale: Margination requires selectin-mediated rolling (A), integrin-mediated
adhesion (B), and cytokine-up-regulated adhesion molecules (C). Histamine
causes vasodilation, not constriction (D incorrect).
, 1.2 Fluid & Electrolyte Shifts
Part A – Competency & Key Concepts
● Objective: Predict edema or dehydration based on Starling forces and ADH/RAAS
responses.
● Key mechanisms:
○ ↓Plasma oncotic pressure (nephrotic syndrome, liver failure) → peripheral
edema
○ ↑ADH (SIADH) → water retention → dilutional hyponatremia
○ Aldosterone escape vs. aldosterone breakthrough
Part B – Deep-Dive Mechanism
In nephrotic syndrome, massive albuminuria drops serum albumin below ~2 g/dL. The
reduced intravascular oncotic pressure no longer counterbalances hydrostatic pressure,
so fluid filters into interstitial spaces, producing periorbital and pedal edema. Despite
falling plasma volume, ADH and aldosterone are activated, causing renal sodium and
water retention. However, because the primary defect is low oncotic pressure, the
retained fluid simply leaks into the interstitium, worsening edema.
Part C – Clinical Application
Scenario: A 7-year-old boy with nephrotic syndrome has 3+ pitting edema and serum
Na⁺ 128 mEq/L.
Q: Why is hyponatremia dilutional rather than depletional?
Answer: ADH-driven water retention exceeds sodium retention, expanding total body
water and lowering serum Na⁺ despite normal total body sodium.
Part D – Competency Assessment
1. Which finding best supports that edema is due to decreased plasma oncotic
pressure rather than increased hydrostatic pressure?
