Electrolyte Unit Flashcards
What are the electrolytes of concern?
Sodium, potassium, chloride
What state do sodium, potassium, and chloride exist in? What does this allow for?
- Exist primarily as free ions, bind ‘weakly’ to other molecules (relative to calcium and magnesium)
- Allows for easy movement down electrochemical gradients and solubility
What is the primary function of Na/K/Cl?
Maintain electrochemical charge or gradients (electrolytic and osmotic control)
Why charge does a cell have? What effect does this have?
- The cell has a high negative charge due to the presence of ANIONIC molecules (nucleic acids, proteins) therefore must maintain osmotic balance by pumping IN cations (K+)
- Attracts positive from outside of cell, don’t rush in because of cell membrane which acts as a barrier
- Regulation of water absorption and water control
What are the concentrations of sodium, potassium, and chloride inside the cell and outside the cell?
- Na: outside = 135-148mmol/L; Inside = 12mmol/L
- Cl: Outside = 98-108mmol/L; Inside = 2mmol/L
- K: Outside = 2.3-5.5mmol/L; Inside = 150 mmol/:
How is electrolyte distribution and balance in the body controlled?
- Movement of ions
- passive diffusion (via ion channels along gradient)
- active transport (against gradient) -
Selective permeability of membrane
- prevents movement of proteins and phosphates out of cell
How are elongated cells different than round?
- Elongated cells with membranes of differing permeability have asymmetry of inner and outer membranes. This is how we absorb differently
Where is most of sodium, potassium, and chloride found in the cells?
How is fluid distributed throughout the body?
- Extracellular fluid (ECF): all fluid outside the cells, including intravascular fluid (in blood cells and plasma volume - not including volume of blood cells) and interstitial fluid or third space (between cells and outside blood vessels)
-ICF: all remaining fluid (inside cells)
Explain the function of the Na-K-ATPase Pump
- 3 sodium out, 2 potassium in
- Na/K exchange maintains ionic homeostasis, regulates cell volume AND forms basis for water soluble absorption
- Pump creates electrochemical gradient across cell membranes
1. Electrical gradient: (positive and negative charges)
→Outflow of more sodium than inflow of potassium = relatively more negatively charged cytoplasm
→Used to create action potentials (nerve and muscle function)
2. Chemical gradient
→Increased extracellular sodium vs cytoplasm, sodium flows down the gradient into the cytoplasm (via transmembrane proteins, ie SGLT-1, SMVT) →drives many transport processes
Explain the steps of the Na/K-ATPase pump
What does the Na/K ATPase pump require?
- Magnesium dependent (deficiency can impact pump)
- Phosphorylation of ATPase protein during the transport (AKA requires energy)
What is the structure of the Na/K ATPase pump? Can this vary?
- Functional unit of enzyme is heterodimer of two subunit proteins; alpha and beta subunits
- Several isoforms of subunits identified in a variety of tissues, relative proportion of each varies among tissues (tissue-specific).
- Isoforms have different rates of cycling, some tissues need faster rates like the heart
What is the function of the electrochemical gradient in transport into cells and absorption?
- Active absorption of sodium is primary mechanism for passively absorbing Cl-, amino acids, glucose, and water
- Asymmetric distribution of channels/Pumps (basolateral vs luminal membrane) causes Na+ to be pumped OUT of cell and K IN, Na actively pumped OUT into interstitial space (into plasma), generates gradient from luminal side intracellularly
- Na passively moves from lumen to inside the cell, drawing Cl- ions, also monosaccharides, amino acids or others co-transported
How do co-transporters and channels work together?
- Co-transports allow for active transport of molecules against the concentration gradient, they build up in the cell and then asymmetric channels on the basolateral side enables passive diffusion and absorption
- We can save energy just by controlling these ions, efficient system
How is sodium, Cl, K, and water absorbed in the intestine?
- Electrochemical gradient created by Na, K-ATPase pump assists in the absorption of Na..95-100% absorbed.
→Na/Glc co-transport, Na/H exchange and electrogenic sodium absorption/diffusion - Cl co-transported with sodium or enters via paracellular space
- Less known about K absorption (kidney has lots of control)- via colon by passive diffusion or H/K pump…85-90% absorbed
→ Some secretion of K into the lumen, depends on aldosterone - Water absorption is passive along osmotic gradient created by nutrient absorption
- Intestine plays minor role in controlling electrolyte balance, kidneys play major role
What membrane is the Na/K ATPase pump found in?
Basolateral membrane (Asymmetric situation!)
How does sodium get into the cell?
- Diffusion through ion channels of luminal side
- Carrier-mediate transport (facilitated diffusion)
- Use the electrochemical gradient created by NaKATPase as a driving force for cotransport or countertransport of other solutes
How are amino acids absorbed?
- Quantitatively important when AA concentration is low
- Similar Na-dependent transport systems occur for glucose (SGLT-1) and in other cells, i.e. liver, kidneys
- AA comes in with sodium then sodium leaves via Na/K/ATPase pump
What is transcellular distribution of potassium influenced by?
- Insulin, pH, catecholamines, osmolarity, potassium concentration
What occurs to action potential with hyperkalemia?
- CELLS DEPOLARIZE
- RMP is closet to the AP threshold, so cells are more excitable
- Extracellular potassium higher than normal so K does not leak out as fast as it normally would by diffusion (diffusion out slows)
- More K retained inside the cell = RMP shifted up
- Cell reaches AP with smaller graded potentials
- Over-responsive and smaller signals
What occurs to action potential with hypokalemia?
- CELLS HYPERPOLARIZE (MORE POLARIZED)
- Extracellular K decreases, concentration gradient increases
- Greater K diffusion out of cell
- Intracell more negative than normal
- RMP farther from threshold
- Normal signal will not reach threshold
- AP not reached as less responsive to signal
How is action potential influenced by Na/K?
- Membrane potential is maintained by NaKATPase pumps
- Tight control of cell membrane potential (K in, Na outside) is critical for nerve impulse transmission, muscle contraction, and cardiac function
- Muscle, nerve, and endocrine cells have “excitable” membranes
- Tension, transmission, and secretary functions result from the ability to generate and propagate action potentials; dependent on K concentration gradients
How much of REE is from activity of Na/K/ATPase?
~20-40% of REE
Modulations in [K] can cause _______________ and cells cannot ___________________. Give examples
- electrophysical disturbances and cells cannot maintain normal RMP
- Hyperkalemia: membrane depolarizes (5 mmol/L), cannot repolarize → muscle weakness, arrhythmias, 8mmol/L can cause complete cardiac arrest
- Hypokalemia: membrane hyperpolarizes → muscle weakness, decreased smooth muscle contractility, severe case <3.5mmol/L paralysis, alkalosis
Name the three stages of action potentials and what occurs in each stage
- Depolarization: Voltage gated Na+ channels open from outside due to incoming propagating current (-50mV), Na+ rushes IN against concentration gradient instantanously(-ve inside) and PD drops (all voltage gated channels fly open under the initial phase)
- Repolarization: Only milliseconds later voltage gated K open to let K out until -70(slower) (against now +ve PD), meanwhile Na+ ions cease influx and outside channels close again
- Re-establish steady state: K+ voltage gated channels close again after delay (over shoot), NaK-Pump takes over
- Cl passive during this process
Why does K leave the cell slower than Na rushing in during an AP?
K have different permeability so they are slower
How is a resting membrane potential formed?
- K flows out faster (due to electrical force) than Na flows in so the cell becomes negative
- High Na and Cl outside of cell, High K and A- inside cell
- Na/K pump is able to dynamically maintain the PD across the membrane at -70mV
- Membrane is polarized at -70mV
Explain the 6 steps of the electrochemical gradient (RMP) and how it has a negative charge
- High -ve charge in cell, high K+ in cell (more permeable to K+ than Na+); Chemical forces act on K+ to leave cell
- K+ trying to get OUT (passive), Na+ trying to get IN (passive); More K+ leaves cell than Na+ enters due to asymmetry effect of channels distribution, overall a -ve charge develops INSIDE
- Due to a -ve charge INSIDE, electrical differences now acts from inside cell, attracting cations back into cell (slows K+ leaving because of osmotic balance) and greater force for Na+ inside the cell
- Eventually a steady state occurs for PASSIVE movement (charge leaving equals charge combine in -passive), but not neutral, RMP = -70mV
- Cannot maintain steady state, unless unlimited supply of Na+ outside and K+ inside, therefore Na/K/ATP PUMP does this
- Cl- movement is passive due to symmetrical presence of Cl- channels; Cl- PD usually same as RMP
Is -70 the RMP everywhere?
- Different isoforms of NaK pump so charge can be different in other tissues
- Rate of reset of pump = amount of sodium coming in and potassium leaving, leads to charge
Explain K+ Homeostasis
- Extracellular fluid K+ homeostasis is maintained by concerted regulation of kidney and muscle
- ECF continually enters the kidneys via glomerular filtration rate
- During states of K+ loss will reabsorb 100% of K, normally 90% of filtered load reabsorbed by kidney
- Excess ECF K is taken up after a meal driven by insulin
- Excess ECF K after exercise taken up driven by catecholamines
- Activity = loss of ICF K to ECF, more lost to ECF under K deprivation
What are the sources of K+ and how do we lose it?
- Dietary K = 80mEq/day
- Renal Reabsorption
- Loss from muscle occurs during activity
- Lose 9 mEq/day with stool loss
- Urine loss 70mEq/day
What are the 5 functions of the kidney? What are the complications of these functions and how can they be treated?
What is hypernatremia?
- Hypernatremia (serum [Na+] > 145 mmol/L) is a hyperosmolar condition due to a decrease in total body water relative to Na (usually due to water deficiency → osmotic shift of water out of cells → decrease in intracellular water and brain volume)
Name the causes and effects of sodium excess and sodium deficit
- symptoms associated with fluid volume. Affects BP and CNS function
Summarize potassium excess and defficiency causes and effects in a table
What are the AIs for sodium and chloride? What about salt? UL?
- Adult AI for salt = 3.8g/day (note that salt is 40% Na)
- Adult UL: Na = 2.3g, Cl = 3.6g = 6g/day of Salt (NaCl)
- Na intake of 2.3g/d is assoicuated with higher blood pressure (vs. 1.2g/d)
- Pregnancy and lactation: note that AI does not change despite increased tissue building and plasma volume of fetus and added NaCl in milk
What are the food sources of sodium and chloride?
- Dietary chloride consumed as NaCl
- Very high in processed foods
- E.g. canned veggies much higher in sodium than fresh
- UL = 2.3g/d of sodium
What are the AIs for Potassium?
- Diets that contain greater or equal to 4.7g/d are associated with decreased risk of stroke, hypertension, osteoporosis and kidney stones. (related to compensation of sodium)
- Lactation: need higher due to extra K secreted in breast milk
- No UL for food alone
- Kidneys under healthy conditions are good at managing potassium
Name food sources of potassium
- High in fresh fruits and veggies
- Particularly leafy green and root vegetables, vine fruit, also some beans, peas, tree fruits, milk/yogurt, meats
- Use of ‘salt substitutes’ (100% KCl or mixtures of 65% NaCl, 25% Kcl, 10% MgSO4) can increase K intake providing 0.4-2.8g K/tsp
What does processing do to sodium and potassium contents of food?
- Processing cause increased sodium and less potassium
Explain the structure of the kidney
- Juxtaglomerular apparatus - controls blood pressure
- Collecting tubule reabsorbs water and urea
- Urea - waste component, increases osmolarity in the medulla to drive water absorption in the loop of henle (maintains osmolarity)
- Efferent arteriole: capillaries extending from it and hang out around tubules (Peritubular capillaries) and collect nutrients in blood stream. Connect into renal vein and takes to rest of the body
What are the 6 hormones that affect the kidney? What are their functions and where do they act? hat is their net effect?
- Angiotensin II
- Atrial natriuretic peptide (ANP)
- Aldosterone
- AVP or Antidiuretic hormone (ADH)
- Vitamin D3 (Calcitriol)
- Parathyroid hormone (PTH)
Explain the fluid regulation cycle
* If blood volume decreases, serum osmolality and thirst and water intake increase what will happen?
VERY IMPORTANT SUMMARY CARD
What is the physiological response of fluid imbalance
- Just regulating water, not solutes with fluid imbalance
What is the physiological response of sodium imbalance
- Increased salt appetite and thirst
What is the function of the countercurrent multiplier system of the loop of henle?
- Kidneys can dilute urine to 1/6 the osmolarity of plama or concentrate it up to 4x that of plasma → excrete urine of highly variable osmolarity (50-1200mOsm/L).
- An osmotic gradient is formed by the anatomical arrangement and functional characteristics of the countercurrent multiplier system of the loop of Henle
- Important that osmotic gradient be maintained, not dissipated by the vascular system
- Allows efficient disposal of excess solutes and water
Variability important because we have variation in intake
Where are the following things drawn out in the loop of henle:
- Water
- Solutes
What effect does this have?
- Solutes: Up to 65% of solutes can be reabsorbed in proximal tubule (Na, K, Cl); Actively drawn out in the Ascending limb; More can be drawn out in the collecting tubule and distal convoluted tubule. (NONE DRAWN IN DESCENDING TUBULE)
- Water: Drawn out in the descending tubule, has more aquaporins. More water is drawn out as we go down
How much of the filtrate remains after going through the loop of henle?
- 100% of filtrate in bowman’s capsule
- 30% left in outer medulla after reabsorbtion of solutes
- 10% remains at the distal convoluted tubule
- At the end of the collecting duct only 0.5%-5% remains
Explain how the osmotic gradient shifts throughout the loop of henle
- Blood flow goes from the descending limb to the ascending limb
- At first the osmotic gradient is = in the ascending limb
- Water is drawn out of the descending limb as it descends. Osmolarity increases in the filtrate
- As the limb ascends, active transport of solutes comes out into the interstitial fuid and osmolarity then decreases because there is less solute
This diagram kind of sucks because the solute flow is wrong
Explain the process of re-absorption of water via Arginine vasopressin AVP or Anti-diuretic Hormone ADH)
- ADH in the blood binds to ADH receptor
- Activates G protein for phosphirylation of cAMP and protein kinase A
- Activation of protein kinase A causes aquaporin 2 to move to surface of apical membrane
- Water then absorbed into the cell
- Exits into into blood via Aquaporin 3 in basolateral membrane
How does the osmotic gradient change when ADH is low versus high?
- If ADH is low the urine will have high volume and low osmolarity (less water reabsorbed)
- If ADH is high there will be more reabsorbed water thus urine will have a low volume and high osmolarity
Explain the process of re-absorption of sodium via Aldosterone
- Aldosterone in the blood binds to cytosolic receptor causing potassium release into the tubule and sodium release into the cell.
- Meanwhile, sodium enters peritubular flood and K is released into cell
- AKA influx of Na into cells and active pumping of Na into plasma (with Cl following) - Reabsorb sodium with some K loss
- Therefore retains both salt and water
- Also stimulates thirst and ADH release
Aldosterone is a potent _____________
Vasoconstrictor
- Adrenal cortex senses plasma osmolarity based on signals received from angiotensin II. Then sends out aldosterone
