Notes: Cell Physiology & Fluid Homeostasis (Quick Review)

Physiology: study of functions and mechanisms in living systems.
Anatomy vs Physiology: structure vs function; physiology is integrative and connected to pathophysiology.
Physiology draws from Biochemistry, Anatomy, Physics, Cell biology; clinical relevance in vital signs and fluid balance.

Cell is the basic unit of life; cellular function underpins tissue/organ function; many drugs/toxins/diseases act at the cellular level.
Focus on structure–function relationships and clinical relevance.

Information flows DNA → RNA → Protein; DNA replication, transcription, translation.
Reverse transcriptase allows RNA → DNA.

Function: Powerhouse; site of aerobic respiration; ATP via oxidative phosphorylation.
Contains own DNA; maternal inheritance.
Clinical: mitochondrial diseases affect high-energy tissues (e.g., muscle, brain).
Key processes: Oxidative phosphorylation and ATP production.
Final electron acceptor: O₂ → H₂O.
ATP yield: 1\ NADH \rightarrow \approx 2.5\ ATP\quad 1\ FADH_2 \rightarrow \approx 1.5\ ATP

Inner mitochondrial membrane houses ETC complexes I–IV and ATP synthase (Complex V).
Donors: NADH → Complex I; FADH₂ → Complex II.
Electron flow: I/II → III → IV → O₂.
Proton pumping creates a proton gradient (chemiosmosis).
ATP synthase uses the gradient to phosphorylate ADP → ATP.
Inhibitors/uncouplers: Cyanide/CO inhibit Complex IV; Oligomycin inhibits ATP synthase; Uncouplers dissipate the proton gradient.

Rough Endoplasmic Reticulum (RER): Ribosomes; synthesizes secreted/membrane proteins; abundant in secretory cells.
Smooth Endoplasmic Reticulum (SER): No ribosomes; lipid/steroid synthesis; detox; cytochrome P450 enzymes.
Golgi Apparatus: Modifies/sorts/packages proteins; lysosome production; I-cell disease (defective M6P tagging).
Lysosomes & Peroxisomes: Digestive/ detox roles; storage diseases (e.g., Tay-Sachs, Gaucher, Niemann-Pick); peroxisomes beta-oxidize very long-chain fatty acids; Zellweger syndrome.
Cytoskeleton: Microtubules (tubulin) for transport/mitosis/cilia; Microfilaments (actin) for movement/contraction; Intermediate filaments for structure; ciliary defects (Kartagener).

Kartagener syndrome: dynein arm defect → immotile cilia; chronic respiratory infections; infertility; situs inversus.

Mitochondria: mitochondrial myopathies; LHON (optic neuropathy).
Nucleus: progeria (lamin A defect).
Rough ER: cystic fibrosis (misfolded CFTR retained in ER).
Golgi: I-cell disease (M6P tagging failure).
Lysosomes: Tay-Sachs, Gaucher, Niemann-Pick.
Peroxisomes: Zellweger syndrome.
Cytoskeleton: Kartagener; Alzheimer’s disease (microtubule-associated tau dysfunction).

TBW (Total Body Water) includes:
- Intracellular fluid (ICF)
- Extracellular fluid (ECF) = plasma + interstitial fluid
Demographics (approximate):
- Adult males ~60% body weight as water
- Adult females ~50–55%
- Elderly ~50–55%
- Infants ~70–75%
For a 70 kg adult male (example):
- TBW = 0.60 \times 70 = 42\ \text{L}
- ECF = 0.20 \times 70 = 14\ \text{L}
- ICF = 0.40 \times 70 = 28\ \text{L}
- Of ECF: Interstitial = 0.75 \times 14 = 10.5\ \text{L}; Plasma = 0.25 \times 14 = 3.5\ \text{L}
Rule of 60-40-20: 60% body weight water; 40% ICF; 20% ECF; within ECF, interstitial ~75% and plasma ~25%
Osmolarity vs Tonicity:
- Osmolarity: solute particles per liter (mOsm/L).
- Tonicity: ability to affect water movement across a semipermeable membrane.
- Isotonic: no net water movement (e.g., 0.9\%\ NaCl).
- Hypotonic: water moves into cells → swelling/lysis.
- Hypertonic: water moves out of cells → shrinkage (crenation).

Starling forces describe fluid movement across capillary membranes:
- Pc: Capillary hydrostatic pressure – promotes filtration (out of capillary).
- Pi: Interstitial hydrostatic pressure – promotes reabsorption (into capillary).
- πc: Capillary oncotic pressure (plasma proteins, mainly albumin) – promotes reabsorption.
- πi: Interstitial oncotic pressure – promotes filtration.
Net Filtration Pressure: Net\ Filtration\ Pressure = (Pc - Pi) - (\pic - \pii)
- Positive value = net filtration (fluid leaves capillaries).
- Negative value = net reabsorption (fluid returns to capillaries).
Edema: caused by increased filtration, reduced reabsorption, increased capillary permeability, or lymphatic obstruction. Edema can coexist with reduced plasma volume (hypoperfusion).

Isotonic fluids (e.g., 0.9\%\ NaCl): expands ECF (plasma + interstitial) with no net water movement into/out of cells.
Hypotonic fluids (e.g., 0.45\%\ NaCl or D5W): water shifts into cells; expands both ICF and ECF, more effect on ICF; caution for cerebral edema.
Hypertonic fluids (e.g., 3\%\ NaCl): water shifts out of cells into ECF; ICF shrinks, ECF expands; used for severe hyponatremia or cerebral edema.
IV Fluids Summary:
- 0.9% NaCl → expands ECF only.
- D5W → initially expands ECF, but glucose is taken up; water then shifts to ICF.
- 3% NaCl → pulls water out of cells (ICF → ECF).

ADH (vasopressin): from posterior pituitary; increases water reabsorption via aquaporins in kidneys.
Aldosterone: from adrenal cortex; increases Na+ (and water) reabsorption; K+ excretion.
ANP (atrial natriuretic peptide): from heart; promotes Na+ and water excretion → lowers blood volume.
RAAS (Renin-Angiotensin-Aldosterone System): kidney senses low BP/volume; increases volume via aldosterone and vasoconstriction.
Clinical links:
- Hemorrhage: plasma (ECF) loss → decreased ECF volume; osmolarity unchanged; activates RAAS/sympathetic response (vasoconstriction, ADH release).
- Dehydration (hypertonic fluid loss): increased osmolarity; water shifts from ICF to ECF; both compartments shrink; triggers thirst and ADH release.
- Thirst and osmolarity changes drive compensatory responses; decreased plasma volume further activates RAAS and ADH.

Homeostasis: stability of the internal environment despite external changes.
Components: Receptor (sensor), Control Center (usually brain/hypothalamus), Effector (muscles/glands).
Negative feedback: reverses the change; most common (e.g., insulin/glucagon loop for glucose, temperature regulation, BP).
Positive feedback: amplifies the change to completion; usually self-limiting when external event ends (e.g., labor, blood clotting cascade).