Sodium, Potassium, Chloride Flashcards
What are the bodies fluid compartments?
intracellular fluid (ICF) and extracellular fluid (ECF)
* ICF: 65% in cells
* intravascular fluid part of ECF: 5-8% in blood vessels
* interstitial fluid part of ECF: 25% between cells
* transcellular fluid part of ECF: 1-2% in epithilial lined spaces
What is the primary function of Na+, K+, Cl-?
maintain electrochemical charge or gradients (electrolytic & osmotic control) and exist primarly as free ions and only bind weakly to other molecules
relative concentrations of Na+, K+ and Cl- inside vs. outside the cell?
- Na+ Outside Cell = 135-148 mmol/L
- Na+ Inside Cell = 12 mmol/L
- Cl- Outside Cell = 98-108 mmol/L
- Cl- Inside Cell = 2 mmol/L
- K+ Outside Cell = 3.8-5.5 mmol/L
- K+ Inside Cell = 150 mmol/L
Why is the charge of a cell so negative?
due to the presence of ANIONIC molecules (nucleic acids, proteins)
* must maintain osmotic balance by pumping IN cations (K+)
How is lectrolyte distribution and balance in the body controlled?
- movement of ions
- selective permeability of membrane
What is the most ubiquitous pump for electrolyte balance?
Na+-K+-ATPase pump which is responsible for 20-40% of BMR
* 3Na+ out, 2K+ in
* Pump creates electrochemical gradient across cell membranes
Describe the electrical and chemical gradients of the Na+/K+ ATPase
- Electrical: Outflow of more Na+ than inflow of K+ so cytoplasm stays more negatively charged and is used to create AP
- chemical: ↑ extracellular [Na+] vs cytoplasm lets Na+ flow down the gradient into the cytoplasm via transmembrane proteins (ie. SGLT-1, SMVT) which drives many transport processes
What is the Na/K ATPase important for?
- maintains ionic homeostasis
- regulates cell volume
- forms basis for water soluble absorption
Describe the Na/K pump
transmembrane protein and functional units is heterodimer with two 𝝰- and β- subunits, but different isoforms exist so relative proportion of each varies among tissues.
* molecular basis is Mg2+ dependant
* Characterized by the transient phosphorylation of ATPase protein during the transport cycle
Descrive the process of how Na/K ATPase works
- transporter picks up 3Na+ inside cell
- ATP binds phosphorylating 𝝰-subunit and changing conformation to release Na+ outside of cell
- transporter picks up 2 K+ outside of cell
- phosphate group on 𝝰-subunit is hydrolyzed triggering release of K+ inside cell
- Cycle repeats
What does active absorption of Na+ act as a co-transporter?
primary mechanism for passively absorbing Cl-, amino acids, glucose, water through co-transport
* allow for active transport of molecules against the concentration gradient, they build up in the cell & then asymmetric channels on the basolateral side enable passive diffusion & ABSORPTION into circulation
Describe the benefit of the asymmetric distribution of channels and pumps on elongated cells?
Asymmetric distribution of channels/PUMPS (basolateral vs luminal membrane) causes Na+ to be pumped OUT of the cell & K+ IN, Na+ actively pumped OUT into interstitial space (into plasma), generates gradient from luminal side intracellularly
Intestine absorption of Na+, Cl-, K+ and water
- Na+: 95-100% absorbed from luminal side via diffusion by ion channels or facilitated diffusion which is assisted by the Na/K pump on basolateral.
- Cl-: co-transported with Na+ or enters via paracellular space
- K+: 85-90% absorbed via passive diffusion in colon or H/K pump
- water: absorption is passive along osmotic gradient by nutrient absorption
How might Na+ facilitate transport of AAs into the cell?
The Na+ binding to the AA transporter increases its affinity for the AA (Na+ going down its gradient) which then binds and the complex causes a conformation change that brings both molecules in and the Na+ is pumped back out by Na/K ATPase
What are the main sources of K+?
> 90% ICF and ~2% ECF, K+ can usually look after itself
* intestinal absorption from dietary K+
* Loss from muscle with activity
* renal reabsorption
What influences transcellular distribution of K+?
- insulin
- pH
- catecholamines
- osmolarity
- K+ concentration
When does muscle take up excess K+ from ECF?
- after a meal driven by insulin
- during exercise driven by catacholamines
What is the resting membrane potential of the cell and how is it maintained?
the resting potential is generally -70Mv but may very on tissue with the different Na/K pump isoforms
1. High K+ in cell so chemical forces act on it to leave
2. K+ more permeable to get OUT than Na+ to get IN so overall -ve charge occurs
3. -ve charge inside slows K+ leaving and greater force for Na+ to get IN
4. steady state with -ve charge occurs for passive movement assisted by Na/K-ATPase
What are the steps of an action potential?
- stimulus occurs
- depolarization: incoming propagating current (-50mV) opens all voltage gated Na+ channels from outside so Na+ rushes IN against concentration gradient (-ve inside) & PD drops
- repolarization: Only milli secs later voltage gated K+ channel on inside open to let K+ out (slower) (against now +ve PD), meanwhile Na+ ions cease influx & outside channels close again.
- re-establish steady state: K+ voltage gated channels close again after delay
(over shoot), Na,K-PUMP takes over.
What maintains the membrane potential?
Na/K-ATPase pump
* critical for nerve impulse transmission, muscle contraction & cardiac function
What major biological functions require the AP process?
Muscle, nerve & endocrine cells have “excitable” membranes
* Tension, transmission, secretory functions result from the ability to generate & propagate action potentials; dependent on [K+] gradients
Why do excitable membranes depend on [K+] gradients?
Modulations in [K+] can cause electro-physical disturbances & cells cannot maintain normal resting membrane potential
* hyperkalemia
* hypokalemia
Describe hyperkalemia
membrane depolarizes (5mmol/L) and cannot repolarize
* Resting membrane potential is closer to the action potential threshold so cells become more excitable
* extracellular K+ higher than normal and K+ does not leak out as fast as it normally would by diffusion (diffusion out slows) & more K+ is retained inside the cell than normal so resting membrane potential is shifted up (closer to threshold) & cell will reach action potentials with smaller graded potentials (over-responsive to smaller signals)
Describe hypokalemia
membrane hyperpolarizes
* Resting membrane potential is farther from the action potential threshold so cells get less excitable
* As extracellular K+ decreases, the concentration gradient increases so greater diffusion pressure & so more K+ diffuses out than normal and intracellular becomes more negative than normal so normal signal would not reach threshold & AP not reached (less responsive to signal)
What is the result of hyperkalemia?
- muscle weakness
- arrhythmias
- 8 mmol/L can cause complete cardiac arrest
What is the result of hypokalemia?
- muscle weakness
- decreased smooth muscle contractility
- severe cases <3.5 mmol/L paralysis, alkalosis
What factors contribute to water/fluid balance?
water input (2.5L/day) and output (2.5L/day)
* input: absoroption across GI & production by cellular metabolism
* output: excretion in urine and feces &loss through sweat and respiration
What controls osmotic homeostasis and fluid balance?
Na+ and kidneys
* ion transport effects fluid balance effects osmotic homeostasis
What is normal osmotic pressure?
300 mOsm in & out of cells (intracellular, interstitial, plasma)
* cells remain same volume (osmotic equilibrium)
What happens with drinking large amounts of pure water?
↓ [solutes] ↓ ([osmotic])
if uncorrected, water will flow into cells where the osmotic concentration is higher so kidneys quickly excrete water to compensate which increases urine volume of low osmolarity.
What happens with consuming large quantity of salt nuts and no water?
↑ plasma [osmotic]
If uncorrected, cell volume may shrink so kidneys respond by quickly modifying [urine] to excrete more solutes in a decreased volume of urine
How does the kidney compensate for changes in fluid?
By controlling the rate of water excretion via changes in the rate of water reabsorption
What are the main compartments of the kidney?
- cortex: composed of glomerulus, Bowmans capsule, juxtaglomarular apparatus, convoluted tubules
- medulla: composed of collecting ducts and loops of henle
Function of the kidney renal tubules
passive water re-absorption, couples to active re- absorption of solutes (including Na+, K+ & Cl-).
How does solute transport vary depending on the segment of kidney tubules?
- Proximal & Distal tubules have Na,K-ATPase PUMPS that drive an osmotic gradient to re-absorb water.
- Descending limb of Henle is impermeable to ions (no pumps) & draws out water only.
- Ascending limb of Henle has Na,K PUMPS, & draws solute (re-absorbs) out from the tubular fluid.
What is the system of the loop of henle?
Countercurrent Multiplier System
Generates differential osmotic gradient from the anatomical arrangement of loop of henle, which is in turn used along the length of the collecting duct to control the rate of water re-absorption from urine and allows for efficient disposal of excess solutes and water
* Allows kidneys to dilute urine to 1/6 the osmolarity of plasma or concentrate it up to 4x that of plasma so excrete urine of highly variable osmolarity (50-1200 mOsm/L)
What is osmolarity?
the concentration of a solution expressed as the total number of solute particles per liter.
Where is osmolarity typically high and low in the kidney tubules?
- the bottom of the loop of henle is typically ↑ osmolarity, being salty concentrated in NaCl+urea since water drawn out
- distal tubule is often ↓ osmolarity with solutes being reabsorbed
What is the functional unit of the kidney?
the nephron
Each kidney is made up of about a million nephron filtering units which include a filter, called the glomerulus, and a tubule.
What is the two step
- the glomerulus filters your blood
- the tubule returns needed substances to your blood and removes wastes.
What is filtered into the glomerulus?
*100% filtered
Includes *water, *salts, *bicarbonate, *glucose, *amino acids, creatinine, urea
*are reabsorbed in the proximal tubule
How does the filtrate move through the nephron?
- 100% filtered into glomerulus
- up to 65% solutes can be reabsorbed in proximal tubule
- water is drawn out in the descending limb
- solutes reabsorbed in the ascending limb
- about 10% of filtrate left in the distal tubule
- more reabsorption of solutes occurs in the collecting duct
- 0.5-5% of filtrate remains