part 2 Key Concepts: Cellular Injury & Stress

Hypoxia: reduced oxygen delivery to cells via decreased blood flow → ischemia when delivery is low.
Two core cellular hits during hypoxic injury:
- Aerobic metabolism stops in mitochondria (Krebs cycle) → ↓ ATP.
- Cells shift to anaerobic glycolysis → some ATP, but lactic acid produced → intracellular acidosis.
Consequences of ATP depletion:
- Na^+ leaks in, K^+ leaks out; Na^+/K^+ pumps require ATP and slow down → Na^+ and water accumulate in cell → cell swelling (hydropic change).
Consequences of anaerobic metabolism:
- Lactic acid damages membranes, intracellular structures, and DNA.
Overall: hypoxic injury has two main harmful pathways (double-edged sword) that can be reversible if oxygen delivery is restored and nucleus remains intact.
Waste and overuse:
- If metabolism is upregulated (illness, burns, infection) or overuse occurs, excessive waste accumulates and contributes to injury.
Prevention note for nurses: assess and prevent hypoxic injury; intervene to restore oxygen delivery.

Reversible injury:
- Cell membrane compromised but nucleus intact.
- Morphology: plasma membrane blebs; mitochondria swelling; endoplasmic reticulum rupture; ribosomes disperse. If nucleus intact, cell can recover.
Irreversible injury (necrosis):
- Nucleus damaged; necrosis occurs when recovery isn’t possible.
- Nuclear changes: pyknosis/pyknotic (nucleus shrinks), karyolysis/karolytic (nuclear fragmentation), karyolysis/karolytic (nucleus dissolves).
- Necrosis leads to cell rupture and release of contents → inflammation.
Apoptosis (programmed cell death):
- Quiet, orderly cell death; no inflammation; macrophages clean up debris.
- Triggered by wear/damage, telomere shortening, DNA damage; p53 involvement; failure of repair can lead to cancer if DNA damage persists (p53 pathway).

Ischemic necrosis and infarction: tissue death due to prolonged lack of oxygen; dead tissue may become infarcted.
Types of necrosis:
- Liquefactive necrosis: tissue becomes liquid (e.g., brain).
- Coagulative necrosis: architecture preserved; common in heart, kidney, spleen.
- Caseous necrosis: cheese-like appearance; TB.
Gangrene: large necrotic area; types:
- Dry gangrene (coagulative) – dry and shriveled.
- Wet gangrene (liquefactive) – swollen, wet, infection-prone.
- Gas gangrene – gas production (Clostridium) within tissue.
Myocardial infarction: ischemic necrosis of heart muscle due to prolonged oxygen deprivation.

Two boys with hypoxic events: one warm, one very cold.
Key reasoning:
- Warmer boy: higher metabolic rate → higher oxygen use → more ATP depletion → more cell swelling and lactic acid production (more acidotic).
- Colder boy: metabolic rate slowed → less oxygen use → less lactic acid → less acidosis; more salvage potential if oxygen delivery is restored.
pH concept: low pH = acidotic; lactic acid from anaerobic metabolism lowers pH.
Clinical takeaway: environment (temperature) affects hypoxic injury severity and potential for recovery; prioritize restoring oxygen delivery and perfusion.

Stressor: any demand that challenges homeostasis (physical or psychological).
General Adaptation Syndrome (Selye): alarm (recognize stress), resistance (adapt and cope), exhaustion (system depletes).
Four hormonal systems activated by stress (focus on three described): cortisol, epinephrine, norepinephrine; (fourth system not detailed here).
HPA axis concept: stress signals from hypothalamus stimulate pituitary to activate adrenal cortex → cortisol release.

Source: adrenal cortex; glucocorticoid class.
Effects (catabolic):
- Alters glucose, fat, and protein metabolism; promotes energy availability for stress.
- Increases plasma glucose; mobilizes amino acids and fatty acids; ramps up breakdown stores.
- Suppresses inflammation and immune responses.
- Suppresses nonessential functions (reproduction, growth, etc.).
Psychological and systemic effects: can cause mood changes, increased alertness, and potential “roid rage” with exogenous steroids.
Clinical note: chronic stress -> compromised immunity and reduced production of RBCs/WBCs due to cortisol effects.

Source: Epinephrine from adrenal medulla; norepinephrine from neurons.
Effects: "fight or flight" response (rapid, short-term):
- ↑ Heart rate; ↑ peripheral vasoconstriction → ↑ blood pressure.
- Redistribution of blood flow: increased to heart, lungs, brain; decreased to skin, gut, kidneys; ↓ urine output; sweat gland activation.
- Result: improved short-term perfusion to essential organs; potential gut/kidney hypoperfusion under stress.
Clinical signs: rapid pulse, cool/pale skin, reduced GI activity, decreased urine output; diaphoresis (sweating).

In cellular injury, focus on ATP depletion, Na^+/K^+ pump failure, cell swelling, and lactic acidosis.
Distinguish reversible from irreversible injury by nucleus integrity and the presence of inflammatory response after necrosis.
Recognize necrosis types and that infarction refers to tissue death due to prolonged ischemia.
During stress, cortisol is catabolic and immunosuppressive; epinephrine/norepinephrine drive the rapid, systemic fight-or-flight response and perfusion shifts.
In management, increasing oxygen delivery and preserving perfusion help limit hypoxic injury; calcium channel blockers can be used to promote vasodilation and improve blood flow in certain contexts.

Ischemia: reduced blood flow/oxygen delivery; can cause hypoxic injury.
Hypoxic injury: dual damage from ATP depletion and lactic acidosis.
Reversible injury: intact nucleus; potential recovery.
Irreversible injury: nucleus damage (pyknosis, karyolysis); necrosis occurs.
Apoptosis: programmed cell death; no inflammation.
Necrosis: uncontrolled cell death with inflammation; various patterns (liquefactive, coagulative, caseous).
Infarction: tissue death due to prolonged ischemia.
General Adaptation Syndrome: alarm → resistance → exhaustion.
Cortisol: catabolic hormone; increases glucose/fat/protein breakdown; immune suppression.
Epinephrine/norepinephrine: rapid sympathetic activation; ↑HR, vasoconstriction, blood pressure; redistribution of blood flow.