CLS 446 UNIT 2 RENAL & ELECTROLYTES

finished

what percentage of human body weight is water?

~40-75%

what factors decrease body water percentage?

• age

• obesity

• higher body fat

what is water’s general role in the body?

acts as a solvent for body processes

what are the four major functions of water?

• transports nutrients to cells

• determines cell volume by its transport into and out of cells

• removes waste products by way of urine

• acts as body’s coolant by way of sweating

how is water distributed in the body? (learning objective)

• intracellular fluid compartment → 2/3… ~28 L

• extracellular fluid compartment → 1/3… ~10.5 L

  • interstitial fluid = fluid in tissues that lies between and bathes tissues

  • intravascular fluid = plasma compartment

what are the four colligative properties? (learning objective)

• osmotic pressure

• vapor pressure

• boiling point

• freezing-point depression

what happens to the colligative properties when solute is added to solvent?

• vapor pressure → lowered below that of pure solvent

• boiling point → raised

• freezing point → lowered

what does osmotic pressure represent?

hydrostatic pressure that develops and is maintained when two solutions of different concentrations exist on opposite sides of a semipermeable membrane

what does a difference in osmotic active molecules cause?

can cause migration of molecules and create osmotic pressure

ex. glucose, protein, and urea nitrogen

what is osmolality?

a physical property of a solution based on concentration of solutes (millimoles) per kg of solvent (% w/w) and is related to changes in properties of solution relative to pure water

decrease in freezing point and vapor pressure

what is the clinical significance of osmolality?

• osmolality is a parameter to which the hypothalamus responds

• regulation of osmolality affects plasma sodium concentration

• regulation of sodium and water controls blood volume

can be determined through serum or urine

what are the osmolality reference ranges for serum?

275-295 mOsm/kg

what are the osmolality reference ranges for urine (24 hr)?

300-900 mOsm/kg

random = 50 - 1200 mOsm/kg

how can osmolality be measured?

through freezing point depression osmometry or vapor pressure osmometry

calculated osmolality does not account for volatile substances like alcohols

what can cause an abnormal osmolal gap?

• alcohols (ethanol, isopropanol, methanol)

• acetone (ketone bodies)

• organic solvents (benzene, toluene, esters & ethers, xylent)

reference range = 5-10 mOsm/kg

what two blood changes affect water regulation?

changes in blood osmolality and blood volume

what are electrolytes and what are the two types?

ions that carry an electric charge

• anion (-) → anode

• cations (+) → cathode

which electrolytes regulate fluid volume and osmolality and support heart function? (learning objective)

volume/osmolality

• Na, Cl, K

heart rhythm/contractility

• K, Mg, Ca

which electrolytes help enzyme activation and blood coagulation? (learning objective)

enzymes

• Mg, Ca, Zn

coagulation

• Ca, Mg

what are the concentrations of the cations in the plasma (mmol/L)? (learning objective)

cations

• 142 mmol/L

sodium

• 4.0 mmol/L

potassium

• 6.0 mmol/L

calcium

• 2.0 mmol/L

magnesium

• 1 mmol/L

what are the concentrations of the anions in the plasma (mmol/L)? (learning objective)

anions

• 103 mmol/L

chloride

• 27 mmol/L

HCO3-

• 16 mmol/L

proteins

• 5.0 mmol/L

organic acids

• 2.0 mmol/L

HPO4 2-

• 1.0 mmol/L

what are the concentrations of the cations in the interstitial fluid (mmol/L)? (learning objective)

cations

• 145 mmol/L

sodium

• 4.0 mmol/L

potassium

• 2-3 mmol/L

calcium

• 1-2 mmol/L

what are the concentrations of the anions in the interstitial fluid (mmol/L)? (learning objective)

anions

• 116 mmol/L

chloride

• 31 mmol/L

what are the concentrations of the cations in the interstitial water (mmol/L)? (learning objective)

cations

• 12 mmol/L

sodium

• 156 mmol/L

potassium

• 3 mmol/L

calcium

• 26 mmol/L

what are the concentrations of the anions in the interstitial water (mmol/L)? (learning objective)

anions

• 4.0 mmol/L

chloride

• 8.0 mmol/L

HCO3-

• 55 mmol/L

what regulates water and electrolyte balance in the body?

hormones and other substances

what stimulates hypothalamic neurons involved in water regulation?

• increased extracellular osmolarity

• decreased intravascular volume

• angiotensin 2

what stimulates angiotensin II, where does it act, and what does it do? (learning objective)

↑ renin (major stimulus); proximal tubule (site); ↑ NaCl and H₂O reabsorption (effect)

what stimulates aldosterone, where does it act, and what does it do? (learning objective)

↑ Angiotensin II or ↑ plasma K⁺ (major stimulus); distal tubule/collecting ducts (site); ↑ NaCl and H₂O reabsorption (effect)

what stimulates ANP, BNP, and CNP, and what is their effect? (learning objective)

↑ ECF volume (major stimulus); collecting ducts (site); ↓ NaCl and H₂O reabsorption (effect)

what stimulates urodilatin, and what does it do? (learning objective)

↑ ECF volume (major stimulus)_; collecting ducts; ↓ NaCl and H₂O reabsorption (effect)

what stimulates ADH, where does it act, and what does it do? (learning objective)

↑ plasma osmolality or ↓ ECF volume (major stimulus); distal tubule/collecting duct (site); ↑ H₂O reabsorption (effect)

regarding the renin-angiotensin-aldosterone system, what does the system regulate? (learning objective)

• body sodium and water content

• arterial blood pressure

• potassium balance

what is renin? (learning objective)

proteolytic enzyme produced, stored and secreted by cells located in the juxtaglomerular cells of the kidney (cells located in the wall of the afferent arterioles) → catalyzes the conversion of angiotensinogen, produced in the liver, to angiotensin I

what increases the secretion of renin? (learning objective)

• reduction in renal profusion pressure

• stimulation of sympathetic nerves to the kidney

• reduced Na+ concentrations in the distal tubule

what does angiotensin I do? (learning objective)

angiotensin I converted to angiotensin II by ACE found on the surface of vascular endothelial cells which takes place primarily in lungs and kidneys

what does angiotensin II do? (learning objective)

is a potent vasoconstrictor with major effects of:

• stimulation of aldosterone secretion of adrenal cortex

• arteriolar vasoconstriction (increases blood pressure)

• stimulation of ADH/thirst

• enhancement NaCl reabsorption in the PCT which leads to ↑ blood pressure

what does aldosterone do? (learning objective)

stimulates Na+ reabsorption in the distal nephron and the body retains water

how does dehydration activate the RAAS pathway? (learning objective)

low effective circulating volume, sensed by afferent arterioles of the kidney and baroreceptors in the carotid sinus and aortic arch which signals the medullar control centers in brain to increase sympathetic outflow to juxtaglomerular cells

what is included in the family of natriuretic peptides? (learning objective)

• atrial-type natriuretic peptide (ANP)

• brain-type natriuretic peptide (BNP)

• c-type natriuretic peptide (CNP)

what are natriuretic peptides? (learning objective)

induces natriuresis (discharge of Na through urine) and is released in response to intravascular volume expansion → has a reciprocal effect on RAAS & plays an important role in guarding against salt inducing hypertension and moderating CHF

each is tissue specific and independently regulated

what is atrial-type natriuretic peptide? (learning objective)

produced primarily in cardiac atria and released in response to changes in pressure within the atria

what are the functions of ANP? (learning objective)

• reducing venous pressure that occurs with increased blood volume

• increasing vascular permeability

• promoting natriuresis and diuresis

what does ANP do regarding the kidneys? (learning objective)

• increases GFR

• suppresses RAAS which inhibits tubular Na+ reabsorption

• moderates the effects of ADH in the CD which inhibits water reabsorption

what does ANP do regarding the brain? (learning objective)

inhibits salt appetite, water intake & secretion of ADH

what is brain-type natriuretic peptide? (learning objective)

is a hormone produced in cardiac ventricles and is released when pressure within the ventricles increases due to an increase in volume expansion and pressure overload

had a similar effect on cardiovascular, natriuresis, and diuresis is similar to ANP

what overhydration disorders/conditions are associated with increased ADH?

water intoxication/SIADH (inappropriate ADH secretion) → increased secretion of ADH secondary to decreased venous return to the heart

• asthma

• pneumothora

• pneumonia

• positive-pressure ventilation

• COPD

• right-sided heart failure can increase ADH due to ↓ venous return

what can cause inappropriate ADH secretion in SIADH?

increased secretion of ADH in absence of appropriate osmolar or volume stimuli due to:

• hypothyroidism

• pain, fear

• anesthesia or surgical stress

• drugs (morphine, barbiturates and carbamazepine)

• CNS disorders resulting from skull fractures and possible brain tumors

what can cause dehydration?

• deficit of water alone

• deficit of water and sodium

• water imbalance

what is the electrolyte, sodium? (learning objective)

a major cation of extracellular fluid… maintains normal distribution of water and osmotic pressure in extracellular fluid

largely determines osmolality of plasma & kidneys majorly regulate body sodium

what is sodium’s role in active transport? (learning objective)

used in the Na⁺/K⁺ ATPase pump (active transport), which uses ~25% of cellular ATP and ~66% of basal brain energy

prevents Na equilibrium in all cells

where is most filtered sodium reabsorbed? (learning objective)

about 60% in PCT, along with HCO3- and water

what is sodium regulation based on? (learning objective)

• intake of water in response to thirst

• excretion of water

• blood volume status

what is the reference range of sodium? (learning objective)

136-145 mmol/L

what causes hypernatremia?

• profuse sweating

• high salt intake

• decreased ADH

what causes hyponatremia?

• depletion due to vomiting, diarrhea, polyuria

• dilution due to retention of water (edema, cardiac failure)

what specimens can be used to measure sodium? (learning objective)

• serum

• plasma

• whole blood

• urine

• sweat

ISE most common to measure

what is the electrolyte, potassium? (learning objective)

major intracellular cation in the body with a concentration of 20x greater inside

the kidneys regulates potassium balance

what are the functions of potassium? (learning objective)

• regulation of neuromuscular excitability

• contraction of heart

• ICF volume

• hydrogen ion concentration

  • as K is lost, Na and H move into cells creating an alkalosis

what does potassium do to normalize an acute rise? (learning objective)

potassium will uptake from ECT into cells to normalize the acute rise in plasma potassium concentration due to increased intake

what are the three factors that influence the distribution of potassium? (learning objective)

• inhibition of NaK/ATPase pump by certain conditions

• insulin promotes potassium ions entering muscle and liver

• catecholamines promote cellular entry of potassium

how is potassium regulated? (learning objective)

• exercise increases plasma potassium

• hyperosmolality depletes potassium

  • ex., uncontrolled diabetes → water diffused from cells carrying K with the water… with normal kidney function, K will eventually be depleted

• cellular breakdown releases potassium into ECF

what is the reference range for potassium? (learning objective)

3.5-5.1 mmol/L

what causes hyperkalemia? (learning objective)

• IV infusion of potassium solutions

• renal failure

• diabetic ketoacidosis (DKA)

what causes hypokalemia? (learning objective)

• starvation

• alkalosis

• vomiting, diarrhea, intestinal fistulas

what specimens can be used for potassium testing? (learning objective)

• serum

• plasma

• urine

why is serum potassium higher than plasma potassium? (learning objective)

platelets release K+ during coagulation, so serum is ~0.1-0.7 mmol/L

what collection factors can falsely increase potassium? (learning objective)

• tourniquet use

• excessive fist clenching

• exercise

• storing blood on ice

• hemolysis

ISE is the most common method

what is the electrolyte, chloride? (learning objective)

is a major extracellular anion & is significant in water distribution, osmotic pressure, electroneutrality

• passively reabsorbed, along with sodium in the proximal tubules

  • in the ascending limb of the loop of Henle, chloride is actively reabsorbed by the chloride pump

• ingested in diet & almost completely absorbed by intestinal tract

what is the reference range for chloride? (learning objective)

98-107 mmol/L

what causes hyperchloremia? (learning objective)

• dehydration

• kidney disease

• salicylate intoxication (starts as metabolic acidosis)

what causes hypochloremia? (learning objective)

• vomiting

• salt-losing nephritis

• metabolic alkalosis

  • conditions associated with high plasma bicarbonate

what specimens can be used for chloride testing? (learning objective)

• serum

• plasma

• urine

• sweat

ISE is the most common method

what is the electrolyte, bicarbonate? (learning objective)

second most abundant anion in ECF and is a major component of buffering system in blood → makes up about 98 mmol/L of TCO2 in plasma

• consists of physiologically dissolved CO2, CO2 bound to amine group in proteins as HCO3- or CO2-, & carbonic acid

• regulated through reabsorption by proximal (85%) & distal (15%) tubules on kidneys

what can cause increased bicarbonate/hypercapnia? (learning objective)

• vomiting with metabolic alkalosis

• compensatory hypoventilation

• hypokalemia

what can cause hypocapnia? (learning objective)

• renal disease

• diarrhea

• respiratory alkalosis

hypokalemia can increase HCO3- because H+ shifts into cells as K+ leaves, contributing to alkalosis

why can severe diarrhea cause hyperchloremic metabolic acidosis (related to hypocapnia)? (learning objective)

excess loss of NaHCO3-

what causes decreased PCO3 in respiratory alkalosis (related to hypocapnia)? (learning objective)

hyperventilation, which may occur with hypoxemia, salicylate intoxication, CVA, or gram-negative sepsis

what is the reference range of bicarbonate? (learning objective)

23-29 mmol/L

what specimens can be used for bicarbonate testing? (learning objective)

serum & plasma

ISE and enzymatic most common

what does the urinary system consist of? (learning objective)

• two kidneys

  • divided into two distinct areas: outer layer (cortex), inner layer (medulla) & each kidney contains ~1-1.5 million nephrons (functional unit)

• two ureters

• bladder

• urethra

what is the flow of renal filtrate?

1. bowman’s capsule

2. proximal convoluted tubule (PCT)

   • located in cortex

3. descending loop of henle

4. ascending loop of henle

5. distal convoluted tubule (DCT)

   • located in cortex

6. collecting duct

7. renal calyces

8. ureter

9. bladder

10. urethra

what is the flow of renal blood?

1. renal artery

2. afferent arteriole

3. glomerulus

4. efferent arteriole

5. peritubular capillaries

6. vasa recta

7. renal vein

what are the three major renal functions? (learning objective)

1. glomerular filtration

2. tubular reabsorption

3. tubular secretion

summarize glomerular filtration (learning objective)

blood is filtered across the glomerular basement membrane into the bowman’s capsule → high glomerular capillary pressure promotes filtration → semi-permeable glomerular basement membrane is negatively charged & large, which helps repel larger negatively charged molecules like proteins… GFR is volume of blood filtered per minute

remember that the pressure in the glomerular capillaries is high due to the difference in size between the afferent and the efferent arterioles

summarize tubular reabsorption (learning objective)

uses both active and passive transport and is a process throughout the nephron (PCT, loop of henle, DCT, & collecting duct) that returns essential water, electrolytes, and nutrients from the filtrate back into peritubular blood

renal threshold is tied to tubular reabsorption, which is the concentration above which the substance cannot be totally reabsorbed and is excreted in the urine (ex. glucose is 160-180)

what is active transport related to tubular reabsorption? (learning objective)

the substance to be reabsorbed must be combined with a carrier protein that is contained in the membranes of the renal tubular cells and requires the expenditure of energy from ATP

what is passive transport related to tubular reabsorption? (learning objective)

requires no energy and is characterized by movement of a substance from an area of higher concentration to one of lower concentration

water and urea are always reabsorbed through passive transport

summarize tubular secretion (learning objective)

the passage of substances from the peritubular capillaries into the tubular filtrate & has two major functions:

• eliminates substances that were not adequately filtered by glomerulus

• regulation of acid-base balance in the body through secretion of 90% of H+ excreted by the kidney

what is the role of the proximal convoluted tube in both reabsorption and secretion?

reabsorption

• returns valuable substances to the blood

secretion

• secretes products of metabolism

what is the role of the loop of henle?

aids in reabsorption of water, sodium, and chloride

what is the role of the distal convoluted tubules?

adjusts for electrolyte & acid-base homeostasis through hormonal control of ADH and aldosterone

what is the role of the collecting duct?

is the final site for concentration or diluting urine & controls reabsorption of water, sodium, chloride, & urea

how is the nonprotein nitrogen compound, urea, eliminated in renal physiology?

readily filtered by the glomerulus and is reabsorbed in the collecting ducts

how is the nonprotein nitrogen compound, creatinine, eliminated in renal physiology?

readily filtered by the glomerulus but is NOT reabsorbed by the tubulues

how is the nonprotein nitrogen compound, uric acid, eliminated in renal physiology?

readily filtered by glomerulus and undergoes a complex cycle of reabsorption and secretion as it courses through the nephron

how is water balanced in the kidney?

through ADH → ADH increases the permeability of DCT & collecting ducts to water which causes the increase in water reabsorption

increased plasma osmolality or decreased intravascular volume stimulates secretion of ADH from posterior pituitary

how does sodium participate in electrolyte balance in the kidneys?

controlled primarily by RAAS & excreted by the kidneys

how does potassium participate in electrolyte balance in the kidneys?

reabsorbed & excreted by DCT & collecting ducts; excretion controlled by aldosterone

how does chloride participate in electrolyte balance in the kidneys?

passively reabsorbed as a counter-ion when sodium is reabsorbed in PCT