Alterations in Intracellular Functions and Fluid and Solute Balance
Alterations in Intracellular Functions and Fluid & Solute Balance — Comprehensive Study Notes
These notes synthesize the lecture transcript on cellular-level function, fluid/electrolyte balance, solute transport, and acid–base physiology. Use them to replace or supplement the provided slides and concept map.
Organization follows major topics from the transcript, with explicit definitions, mechanisms, examples, and exam-relevant details (including key numbers and formulas in LaTeX where indicated).
Visuals referenced in the slides (e.g., diagrams of glycolysis, Na+/K+ pump, osmosis, RAAS, and membrane potentials) are summarized in bullet form for quick review.
I. Overview: Homeostasis, Fluid Compartments, and Balance
Homeostasis is the maintenance of a stable internal environment despite external changes. Any imbalance in body fluids or electrolytes triggers compensatory responses to restore balance.
Core players in fluid/electrolyte balance and intracellular function:
Osmolality and tonicity govern water movement between compartments.
Oncotic pressure (colloid osmotic pressure) relates to proteins (e.g., albumin) in maintaining fluid distribution.
Hydrostatic pressure drives fluid movement between compartments.
Regulatory systems: RAAS, natriuretic peptide system (ANP/BNP), and ADH (vasopressin).
Principal electrolytes: sodium (Na+), potassium (K+), calcium (Ca2+), chloride (Cl−), phosphate (PO4−).
Metabolic acids produced by cellular respiration affect the internal milieu.
Major views of compartments and terminology:
Intracellular fluid (ICF)
Extracellular fluid (ECF), including plasma (vascular space) and interstitial fluid (tissue space)
Terms often used interchangeably in practice: vasculature, bloodstream, plasma, blood volume, circulation, etc.
Guiding equations and concepts (to be memorized):
Osmolality rules water movement between compartments via osmosis; higher osmolality pulls water toward that compartment.
Normal plasma osmolality: O_{plasma} \,\in\, [280,\,295]\;\text{mosmol/kg}
Normal blood pH: pH\;\in\;[7.35,\,7.45]
Normal saline tonicity: 0.9\%\;\text{NaCl} is isotonic to blood (often referred to as NS).
Clinical aim: monitor and correct fluid, electrolyte, and acid–base imbalances to restore ATP production and cellular function.
II. Hypoxia and Cellular-Level Function
Hypoxia is a decrease in oxygen delivery/utilization at the cellular level with a spectrum of etiologies (exercise, respiratory failure, vascular injury).
Cellular response to hypoxia:
Shift from aerobic glycolysis to glycolysis (anaerobic metabolism) to generate ATP when oxygen is limited.
Anaerobic glycolysis yields 2\;\text{ATP per glucose} but produces lactic acid, contributing to acidosis.
Advantages: temporarily sustains energy; Disadvantages: insufficient ATP long-term; lactate accumulation → acidosis.
Consequences of hypoxia:
Acid–base disturbance: increased acid production and potential metabolic acidosis if lactate accumulates.
ATP depletion if ATP production cannot meet cellular demand.
Notable points:
If hypoxia persists, cells accumulate pyruvate → lactate; lactic acidosis may ensue.
Hypoxia-related metabolic derangements are foundational to many disease processes and S&S (e.g., signs of poor oxygenation).
Quick recap of the oxygen pathway:
Aerobic metabolism (with O2) -> efficient ATP production; Anaerobic metabolism (without O2) -> less ATP, lactic acid buildup.
III. Nutritional Alterations and Back-Up Metabolic Pathways
Glucose and vitamins are essential for ATP production; access to nutrients is regulated by hormonal control and storage pathways.
Normal glucose handling (fed state):
Blood glucose rises after a meal; pancreas secretes insulin to promote cellular uptake of glucose; excess glucose is stored as glycogen in the liver (glycogenesis).
If glucose exceeds immediate needs, insulin triggers glycogenesis to store glucose as glycogen.
Term: glycogenesis (formation of glycogen).
Fasting/low glucose state (counterregulatory response):
Hypoglycemia triggers counterregulatory hormones: epinephrine, cortisol, growth hormone (GH), glucagon.
Primary back-up plan after glycogen stores are exhausted: glycogenolysis (breakdown of glycogen to glucose).
After glycogen stores are depleted, the body may use fats and proteins for energy: this is lipolysis/proteolysis leading to ketone production (ketogenesis) and/or gluconeogenesis.
Key back-up processes:
Glycogenolysis: breakdown of glycogen to glucose (liver/glycogen stores).
Gluconeogenesis: creation of glucose from non-carbohydrate sources (e.g., amino acids like alanine, glycerol, lactate).
Ketogenesis: production of ketone bodies from fatty acids; ketones can serve as energy for some tissues but are acidic and brain requires glucose.
Important roles of hormones in energy balance:
Insulin: promotes glucose uptake and storage; enhances glycogenesis.
Glucagon: stimulates glycogenolysis and gluconeogenesis to raise blood glucose during hypoglycemia.
Epinephrine, cortisol, GH: counterregulatory hormones that promote glycogenolysis, gluconeogenesis, lipolysis.
Clinical significance of backup pathways:
Type I diabetes mellitus: lack of insulin leads to sustained gluconeogenesis and lipolysis; risk of hyperglycemia, ketoacidosis, and weight loss.
Glycogen storage diseases (e.g., McArdle disease): impaired glycogenolysis leads to muscle weakness during exercise.
Prolonged gluconeogenesis can lead to excess ketone production and metabolic acidosis.
Brain energy needs:
Brain cells depend heavily on glucose; prolonged hypoglycemia can lead to cognitive deficits, unconsciousness, seizures, or death.
Vitamin deficiencies (particularly in alcoholics) impact metabolic pathways:
Thiamine (B1) deficiency → Wernicke–Korsakoff syndrome; beriberi; neurologic symptoms common.
Other B vitamins and iron deficiencies can impact electron transport chain (ETC) and ATP production.
Toxic exposures and some drugs can impair vitamin absorption and metabolism (e.g., cyanide poisoning disrupts cytochrome c oxidase, see below).
Examples and implications:
Type I diabetes and sustained gluconeogenesis → hyperglycemia and ketosis; risk of ketoacidosis.
Alcoholism frequently accompanies nutritional deficiencies, leading to neuro and systemic symptoms.
Viruses, toxins, and drugs can alter metabolic pathways by affecting enzymes or cofactors.
IV. Solute Status and Electrolyte Balance
Quick overview of key solutes:
Proteins: plasma proteins (e.g., albumin) regulate oncotic pressure; intracellular proteins contribute to intracellular anions.
Glucose: energy source; hyperglycemia can drive osmotic shifts.
Electrolytes: Na+, K+, Ca2+, Cl−, PO4−; move as ions and influence water distribution and electrical properties of cells.
Major compartments and solutes:
Plasma (intravascular) contains Na+, Cl−, proteins; interstitial fluid surrounds cells; intracellular fluid has high K+ and low Na+.
Osmolality and tonicity determine water movement between compartments.
Key concepts:
Diffusion and osmosis drive solute and water movement; water moves toward compartments with higher solute concentration (higher osmolality).
Isotonic fluids have tonicity ~0.9% NaCl; hypotonic and hypertonic fluids create shifts between compartments.
Important numeric references:
Normal osmolality of body fluids: O_{normal} = [280, 295]\ \text{mosmol/kg}
Isotonic saline: 0.9\%\;\text{NaCl} (NS). Isotonic to blood.
Solute balance and blood–tissue dynamics:
A rise in plasma solute concentration (hyperosmolar state) pulls water from tissues into plasma (B→T to restore balance, or T→B depending on context).
A decrease in plasma osmolality (hypoosmolar state, e.g., SIADH with excess ADH or protein loss) can pull water from plasma into tissues, causing edema.
Correlates of osmolality:
Osmotic pressure correlates with osmolality; oncotic pressure (protein-based osmotic pressure) also contributes to fluid distribution.
Clinical terminology around osmolar states:
Hypernatremia or hyponatremia describe Na+ imbalances driving tonicity changes.
Hypercalcemia or hypocalcemia describe Ca2+ changes affecting membrane permeability and excitability.
SIADH increases ADH, causing water retention and dilutional hyponatremia; oliguria occurs due to fluid retention.
Domino effects in solute shifts (therapeutic example):
Potassium supplementation increases plasma K+, which diffuses into tissues, potentially causing hypokalemia in blood over time if not managed; this demonstrates the B-to-T diffusion dynamic.
Practical takeaways for nurses:
When hypernatremia/hyperosmolality occurs, expect cellular dehydration and potential edema in tissues as shifts occur.
When hyponatremia/hypoosmolar states occur, expect water movement into cells, potential cellular swelling and neurologic symptoms.
The balance of Na+, K+, Ca2+, and proteins (albumin) underlies many shifts and outcomes such as edema or dehydration.
V. Fluid Shifts, Osmosis, and Volume Regulation
Fluid movement basics:
Water shifts between plasma, interstitial, and intracellular spaces are governed by osmosis and osmolality differences.
Water moves from lower osmolality (more dilute) to higher osmolality (more concentrated).
Fluid compartments:
Plasma (intravascular space) vs interstitial fluid (tissue space) vs intracellular fluid (cell interior).
The capillary bed is the site where plasma water exchanges with interstitial fluid, and then water can move into and out of cells.
Osmolality and tonicity:
Osmolality measures solute particle concentration per kg of solvent; tonicity is the effective osmolality that influences water movement across membranes.
Normal tonicity of blood is isotonic to normal saline (~0.9% NaCl).
Correlates and terms:
Hypertonic (hyperosmolar): higher osmolality than normal; water moves from cells to the extracellular space.
Hypotonic (hypoosmolar): lower osmolality than normal; water moves from extracellular space into cells.
Key practical examples:
Isotonic fluids (NS, 0.9% NaCl) do not cause net water movement between compartments.
Hypotonic fluids (e.g., 0.45% NaCl) draw water into cells, potentially causing cellular swelling.
Hypertonic fluids (e.g., 3% NaCl) draw water out of cells into the plasma, risking cellular dehydration but increasing intravascular volume.
Osmolality rules and practical checks for practice exams:
If osmolality rises (hyperosmolality), water shifts from tissue to blood (T→B) to restore balance.
If osmolality falls (hypoosmolality), water shifts from blood to tissue or intracellular space (B→T).
RAAS and ADH in volume regulation:
RAAS responds to low blood volume or low BP by stimulating vasoconstriction and aldosterone-mediated Na+ and water retention.
ADH (vasopressin) promotes water reabsorption in the kidneys to conserve water.
ANP/BNP promote diuresis when volume is high to decrease circulating volume.
Practical note for edema vs dehydration:
Edema can result from increased hydrostatic pressure, decreased oncotic pressure (hypoproteinemia), lymphatic obstruction, or Na+ and water retention via hormonal pathways.
Dehydration (volume deficit) shows poor skin turgor, dry mucous membranes, sunken eyes, oliguria, and increased serum osmolality.
VI. Acid–Base Balance: Sequelae of Solute Imbalances
Quick review of acid–base basics:
Blood pH normal range: pH\in[7.35,7.45].
Blood gas analysis involves pH, HCO3−, and PCO2 (and often PO2/SO2).
Definitions:
Acidosis: pH < 7.35
Alkalosis: pH > 7.45
Types of acid–base disorders:
Metabolic acidosis: low HCO3− and low pH; compensation via hyperventilation (blowing off CO2).
Metabolic alkalosis: high HCO3− and high pH; compensation via hypoventilation (retaining CO2).
Respiratory acidosis: high CO2 with low pH; compensation via increased HCO3− via kidney adjustment.
Respiratory alkalosis: low CO2 with high pH; compensation via decreased HCO3− via kidney adjustment.
Common metabolic acidosis etiologies:
Diabetic ketoacidosis (DKA)
Lactic acidosis from hypoxia or sepsis
Kidney failure (inability to excrete acids or reabsorb bicarbonate)
Severe diarrhea (loss of bicarbonate)
Common metabolic alkalosis etiologies:
Vomiting (loss of HCl)
Excess bicarbonate intake (e.g., antacids) or renal loss of acid
Compensation principles (focus for exams):
If metabolic acidosis, lungs hyperventilate to reduce CO2; pH moves toward normal (compensation).
If metabolic alkalosis, lungs hypoventilate to retain CO2; pH moves toward normal (compensation).
If respiratory acidosis, kidneys increase HCO3− reabsorption; if respiratory alkalosis, kidneys decrease HCO3− reabsorption/excretion.
Example ABG interpretations (from slides):
pH = 7.28, HCO3− = 19: metabolic acidosis (low pH, low HCO3−; CO2 not shown) with renal/kidney/metabolic cause.
pH = 7.50, HCO3− = 30: metabolic alkalosis (high pH, high HCO3−).
Practical exam tips:
For the upcoming test, focus on metabolic ABGs and HCO3 changes; if HCO3 is abnormal, identify the acid–base disorder, then consider compensation (respiratory or renal) and the likely primary problem.
ABG interpretation workflow: determine pH, assess whether the primary disorder is metabolic or respiratory based on HCO3− or CO2, then identify compensation and time course.
Additional notes:
DKA and lactic acidosis both contribute to metabolic acidosis and may present with hyperkalemia due to the shift of K+ during acidosis.
Ketoacidosis may present with ketonuria and acetone breath; ketone bodies are acids and can worsen acidosis if not controlled.
VII. Hypovolemia, Hypervolemia, and Hormonal Compensation
Fluid volume deficit (dehydration) signs:
Tenting of skin, dry mucous membranes, sunken eyes, oliguria, increased serum osmolality, and possibly tachycardia and hypotension.
Hormonal compensation in fluid deficit:
RAAS activation: reduced renal perfusion or increased plasma osmolality triggers renin release, angiotensin II formation, and aldosterone secretion.
Aldosterone promotes Na+ and water retention to increase circulatory volume.
ADH promotes water reabsorption; contributes to concentrated urine and fluid conservation.
RAAS cascade (simple flow):
Kidney senses low volume/osmolality → Renin release → Angiotensin I → ACE converts to Angiotensin II → Vasoconstriction and aldosterone release → Na+ (and water) retention; blood pressure and volume increase.
Natriuretic peptide system (NPS):
In volume overload, atria and ventricles secrete ANP and BNP to promote diuresis and natriuresis; reduces circulating volume.
SIADH (syndrome of inappropriate ADH):
Causes excessive ADH release → water retention → dilutional hyponatremia; oliguria.
Clinical implications of edema vs dehydration:
Edema is fluid accumulation in interstitial space due to shifts in osmolality, decreased oncotic pressure, lymphatic disruption, or hydrostatic forces.
Dehydration is a deficit of water in the circulating volume, with concentrated plasma and signs of hypovolemia.
VIII. Acute and Chronic Toxins: Cyanide and Related Mechanisms
Cyanide toxicity mechanism:
Cyanide binds to ferric iron in cytochrome oxidase (Complex IV) in the electron transport chain, inhibiting oxidative phosphorylation.
Result: histotoxic cellular hypoxia; cells cannot generate ATP via aerobic metabolism; shift to anaerobic glycolysis leads to lactic acidosis.
Clinical consequence:
Metabolic acidosis due to lactate accumulation; impaired tissue oxygen utilization despite normal oxygen delivery.
Practical note:
Cyanide toxicity can occur via exposure to certain insecticides, rodenticides, smoke inhalation from burning materials, or some drugs; early recognition is critical due to rapid deterioration.
IX. Vitamins, Deficiencies, and Nutritional Impacts on Metabolism
Alcohol use and vitamin deficiencies:
Common deficiencies in chronic alcoholism: thiamine (B1), folate, others; lead to neurologic manifestations (e.g., Wernicke–Korsakoff syndrome, peripheral neuropathies).
Beriberi: thiamine deficiency; neurologic and cardiovascular symptoms.
Thiamine (B1) role:
Essential cofactor for carbohydrate metabolism (pyruvate dehydrogenase complex) and the TCA cycle; deficiency disrupts ATP production.
Associated neurologic syndromes:
Wernicke–Korsakoff syndrome: memory loss, ataxia, ophthalmoplegia; confusion and neuropathies may be present.
Paresthesia: tingling or numbness; seen in B12 deficiency and other neuropathies.
Nutritional deficiencies and fluid balance:
Hypoproteinemia (low plasma protein) reduces oncotic pressure, contributing to edema and altered fluid shifts (blood-to-tissue movement).
Protein loss in kidney disease (proteinuria) leads to hypoalbuminemia and edema; affects plasma oncotic pressure and osmolality balance.
Practical implications for nursing:
Assess for signs of malnutrition, alcohol misuse, and vitamin deficiencies in at-risk patients.
Monitor for edema, hypoalbuminemia, and related fluid-shift symptoms; consider nutritional interventions and supplementation as indicated.
X. Special Topics: Exercise-Related Physiology, Metabolic Pathways, and Pathologies
Glycolysis and the metabolic pathway (overview):
Glycogenesis: formation of glycogen from glucose; glycogen storage in liver and muscle.
Glycogenolysis: breakdown of glycogen to glucose; provides rapid glucose during fasting or exercise.
Glycolysis (anaerobic): glucose → pyruvate → lactate when oxygen is limited; yields 2 ATP per glucose.
Gluconeogenesis: synthesis of glucose from non-carbohydrate sources (e.g., lactate, glycerol, amino acids); active during fasting to maintain blood glucose.
Lipolysis: breakdown of fats to provide fatty acids for energy; ketogenesis forms ketone bodies when glucose is scarce.
Ketogenesis: production of ketone bodies (acetone, acetoacetate, beta-hydroxybutyrate) from fatty acids; can contribute to acidosis if excessive.
TCA cycle (Krebs) and oxidative phosphorylation provide high-yield ATP under aerobic conditions.
Experimental and concept map connections:
The metabolic pathway map links normal function to disease states. Disorders of glycogen storage, glucose utilization, and vitamin deficiencies disrupt ATP production and cellular function.
Practical exam notes:
Expect questions linking energy pathways to clinical states (e.g., hypoglycemia, DKA, lactic acidosis, metabolic/alveolar compensation).
Remember that brain energy requirements emphasize glucose dependence; ketones are insufficient for complete brain energy needs.
XI. Practice, Policies, and Exam Readiness
Exam logistics and rules (as per slides):
Environmental scans and webcam positioning instructions; ensure visibility of environment, testing surface, computer, and any permitted aids.
No electronic devices or speaking during certain portions; memory aids must be handwritten on one side of one watermarked page; no additional writing during exam; memory aids must be uploaded within 24 hours of exam start; late submission incurs penalties.
Handwritten memory aids should use color differentiation to outline topics; use sheet protectors if needed; avoid using digital handwriting during the exam.
Practice items from the transcript:
Understand the difference between hypoxemia (low blood oxygen) and hypoxia (insufficient oxygen delivery to tissues).
Be able to perform quick ABG interpretation focusing on metabolic disturbances and their compensations.
Distinguish osmolality, tonicity, osmosis, and oncotic pressure; apply to fluid shifts and edema/dehydration scenarios.
Key recall prompts:
Define the following: osmolality, tonicity, oncotic pressure, RAAS, ADH, ANP/BNP, hypopolarization, hyperpolarization, RMP, and the normal ABG ranges for pH, HCO3−, and PCO2.
List the metabolic backup pathways in order: glycogenolysis, gluconeogenesis, lipolysis/ketogenesis, and the conditions that activate each.
Identify clinical signs of dehydration (e.g., tenting, dry mucous membranes, oliguria) and edema (e.g., pitting edema, pulmonary edema, CNS changes).
Summary of Key Equations and Numbers (for quick reference)
Normal plasma osmolality: O_{plasma} \approx 280\text{--}295\;\text{mosmol/kg}
Normal blood pH: pH\in[7.35,7.45]
Isotonic saline concentration: 0.9\%\;NaCl\quad (\text{NS})
Resting membrane potential: RMP = -90\ \text{mV}
Depolarization goal (contraction): +30\;\text{mV}
Anaerobic glycolysis yield: \text{ATP} = 2\ \text{per glucose}
ATP production: aerobic metabolism yields higher ATP than anaerobic glycolysis (not a single number here, but understood from glycolysis vs oxidative phosphorylation).
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