Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathophysiology - Urinary Tract > Disorders of Acid-Base Regulation > Flashcards

Disorders of Acid-Base Regulation Flashcards

1
Q

Give the Henderson Hasselbach Equation.

A

pH = 6.1 + log (([HCO3-]) / (0.03 *pCO2))

The 0.03 is based on dissolved carbonic acid, and varies with the elevation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the difference between a volatile and nonvolatile acid? Give some examples of the latter.

A

Volatile - potential acid which can be evaporated. I.e. CO2 from daily metabolism

Nonvolatile - acids which cannot be evaporated.

Examples:
Sulfur-containing amino acids -> degrade to sulfuric acid
positively charged AA -> HCl
Phosphates also contribute -> phosphoric acid

negatively charged AA and organic anions -> produce bicarbonate, which buffers some of this.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why do we need to keep making HCO3-? How does the kidney function in this?

A

We make about 1 mEq/kg/day of nonvolatile acids which need to be buffered by bicarbonate system.

When they are buffered, they rapidly form CO2 gas which is loss (volatile gas). This HCO3- then needs to be replaced. Kidney functions to excrete the sodium salts that are made from this conversion and replenish the HCO3- by secreting acid EXACTLY EQUAL to the nonvolatile acid produced, and reclaim filtered HCO3-.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is total H+ secretion by the tubules equal to? (sum of other H+ secretions)?

A

Total H+ secretion = H+(HCO3-) + H+(NH4+) + H+(TA)

H+ total = H+ for reabsorption of bicarbonate + H+ in the form of NH4 + H+ in another titratable acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the net acid secretion then / how is it calculated?

A

Net acid secretion = [(Excreted NH4 + Excreted TA)] - [Excreted HCO3-]

Excreted HCO3- is bicarbonate which wasn’t reabsorbed

Excretion can be calculated by the urinary concentration of the substance times the urine flow rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the transporters which help reabsorb bicarbonate in the proximal tubule on both the apical and basolateral membranes?

A

Apical - H+-ATPase (Vacuolar), Na/H exchanger

Basolateral - 3HCO3/Na cotransporter (driven by relatively positive ECF), HCO3-/Cl- antiporter (AE1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the function of carbonic anhydrase in the proximal tubule?

A

Speeds formation of CO2 + H2O which would normally be very slow after formation of carbonic acid (rate limiting step)

This facilitates reabsorption of carbon dioxide and water rapidly into the cell, where carbonic anhydrase inside can reform HCO3-.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the mechanism of reabsorption of bicarbonate in the TALH?

A

Same as in proximal tubule, just with less carbonic anhydrase on the apical membrane, making it slower

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What cell is responsible for acidifying the urine? What apical transporters does it do this with?

A

Alpha-intercalated cell, relatively impermeable to H+ aside from transporter -> can bring urine pH down to 4.0

V-ATPase (H-ATPase) on apical surface
+
H,K-ATPase - the exchanger

These can be used to reabsorb existing bicarbonate from the tubule lumen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the function of the beta intercalated cell and what transporter does it have at the apical and basolateral membranes?

A

For secretion of bicarbonate (bases) in the lumen, rarely needed except in vegans who can have base excess. Basically a mirror image of an alpha intercalated cell.

Apical transporter - Pendrin** - functions like AE1/AE2 but not the same. HCO3- out with Cl- in.

Basolateral transporter - V-ATPase, pumps H+ out. Cl- also passively reabsorbed into blood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why is a non-bicarbonate buffer needed to generate new base (new HCO3-)?

A

If it was bicarbonate, H+ would be pumped into the lumen and combine with HCO3- and form CO2, which is another acid. We will have effectively reabsorbed that acid.

In this case, H+ stays in the lumen and the bicarbonate generated by carbonic anhydrase from this isn’t matched by the degradation of one in the tubular lumen. This allows that acid to be ACTUALLY EXCRETED in the urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two most important non-bicarbonate buffer systems? Where do they come from?

A

NH3/NH4+ = produced by kidneys, regulated by acid-base status -> makes up the majority of net acid excretion

HPO4-2/H2PO4- = titratable acid derived from diet, filtered at glomerulus, does not change with acid-base status

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Where and how is ammonia made in the nephron? How does this help us excrete acid?

A

Glutamine is converted to alpha-ketoglutarate and two NH4+ in the proximal tubule via the enzyme phosphate dependent glutaminase (PDG), or only one by glutamine deamidase

Each NH4+ is secreted into the lumen in the place of H+ for the Na/H exchanger

The two NH4+ forms two bicarbonate which leave at basolateral membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does the TALH do with ammonium?

A

Reabsorbs it via the NKCC transport, substituting for K+

Then, NH4+ leaves substituting for K again with the Na/K ATPase or normal K+ channel (wants to go out)
-> concentrates the medullary interstitium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens to NH4 in the medullary interstitium / how is it uptaken by the collecting duct?

A

NH3 / NH4+ is in equilibrium
It is taken up by the alpha-intercalated cell by one of two mechanisms:
1. Na/K ATPase in place of K
2. Rhcg channel (protein is in Rh antigen family)

Then is secreted into tubular lumen by Rhcg channel

NH3 will be again protonated by H+ secreted by alpha intercalated cell, finally resulting in a complete loss of acid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens if the NH3 in the medullary intersitium does not re-enter the alpha intercalated cell to be excreted?

A

ammonia will enter bloodstream and be made into urea and secreted, the H+ it was carrying will never be lost, and there is no net acid secretion.

-> secretion by alpha intercalated cell is critical for maintaining acid-base balance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does systemic pH affect the action of the NH3/NH4 system?

A

low pH stimulates proximal tubule glutamine deamidase
high pH inhibits it

-> secrete more acid in the form of NH4+ when you need to.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do plasma potassium levels affect the NH3/NH4 system?

A

Hypokalemia - stimulates NH4+ production and increases Rhcg expression, and stimulates H+,K+ ATPase (hypokalemia will predispose to alkalosis)

Hyperkalemia - does opposite, inhibits NH4+ production (hyperkalemia will predispose to acidosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do ECF expansion and ECF contraction alter bicarbonate reabsorption?

A

ECF expansion - lowers bicarbonate absorption by lowering proximal tubule Na reabsorption (time for Na/H activity at high volumes)

ECF contraction - increases bicarbonate and sodium reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the mechanism of increased or decreased normal (not NEW) bicarbonate reabsorption in response to alkalosis or acidosis?

A

Acidosis - more bicarbonate reabsorption
Alkalosis - less bicarbonate reabsorption

Mechanism - lower intracellular pH of alpha-intercalated cell favors secretion of H+ (lower cell-to-lumen gradient to push against via ATPase), and thus bicarbonate reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does aldosterone stimulate H+ secretion (bicarbonate reabsorption)?

A

Directly -> stimulates H+ secretion by alpha intercalated cells

Indirectly -> stimulates Na+ reabsorption by principle cells, generating a negative lumen potential, which favors secretion of H+ by alpha intercalated cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does increasing angiotensin II affect bicarbonate reabsorption? How does this mechanism relate to blood pCO2 as well?

A

Directly increases number of proximal tubule Na/H exchangers, which increases H+ secretion and hence HCO3- reabsorption
-> increased pCO2 does the exact same thing

-> this is the mechanism responsible for contraction alkalosis (more bicarbonate absorption than usual when AT2 levels are high)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is acidosis vs acidemia?

A

Acidosis - a process which, if left unopposed, will lead to acidemia

Acidemia - drop in pH below 7.35 (7.40 in Rossi’s world)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the difference between a metabolic and a respiratory acid-base disorder?

A

Metabolic - characterized by a PRIMARY change in HCO3-

Respiratory - characterized by a PRIMARY change in pCO2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How do plasma HCO3- levels change in respiratory acidosis (not yet compensated) and why?

A

Plasma levels rise -> carbonic reaction is driven to the left because of addition of pCO2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How is acid-base buffered in the body intracellular / extracellular outside of the bicarbonate system?

A

H+ buffered by hemoglobin, as well as phosphates and plasma proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the renal compensation of metabolic or respiratory acidosis?

A

Stimulation of tubular H+ secretion

  • > enhanced reabsorption of filtered HCO3-
  • > Increased net acid excretion via production of ammonia
  • > HCO3- will return pH back to normal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is it more difficult for the kidney to compensate conditions of alkalosis?

A
  1. Inhibition of tubular H+ secretion may be overridden by ECF concern -> want to take up as many ions as possible
  2. Reduction of HCO3- secretion is difficult for the reason mentioned above
  3. Metabolic alkalosis often accompanied by hypokalemia -> stimulates acid secretion and further predisposes to alkalosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How is the compensatory fall in pCO2 for metabolic acidosis calculated?

A

Fall in pCO2 = 1.0 -1.3 mmHg * (fall in HCO3-)

HCO3- is assumed to be 25 mEq/L at baseline
pCO2 is assumed to be 40 mmHg at baseline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What causes an increased vs a normal plasma anion gap acidosis, conceptually?

A

Increased - addition or production of an acid which leaves an unmeasured anion in the blood

Normal - caused by addition of HCl (Cl- is measured in blood), or primary loss in HCO3- (excretion of HCO3- is paired with reabsorption of Cl-)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How do you calculate a plasma anion gap, and what is a normal gap?

A

Anion gap = [Na] - ([Cl-] + [HCO3-])

Normal gap = 10 mmol/L

140-(105+25) = 10

32
Q

What type of acid-base disorder will a renal tubular acidosis cause and how? What type of kidney does this have to happen in?

A

Normal plasma anion gap
-> renal tubular acidosis is due to impaired urinary acidification (impaired renal H+ excretion)

  • > Happens in a healthy kidney with no other underlying cause
  • > it’s not called a renal tubular acidosis if you have advanced chronic kidney disease and that’s the reason why you can’t excrete acid
  • > failing kidneys will make maximally acidic urine but just have low urine flow
33
Q

What is the urinary anion gap useful for and how is it calculated? What is a normal urine value?

A

Useful for the differential diagnosis of normal plasma anion gap metabolic acidosis

Based on the assumption that HCO3- and other unmeasured anions in the urine are negligible, and charges will equal out

0 = ([NH4+] + [Na+] + [K+]) - ([Cl-] + [Unmeasured anions])
Since NH4+ is difficult to measure, we can calculate the anion gap by assuming there are only four cations in the urine. Thus, we can say that

UAG = -[NH4+] = [Na+] + [K+] - [Cl-]

In normal urine, this gap is zero or slightly negative.

34
Q

How does the urinary anion gap change if the kidney is properly responding to normal plasma anion gap metabolic acidosis and why?

A

Normal response would be to increase renal tubule acid secretion in the collecting duct. This is done by increasing ammonia excretion. Since ammonia will be excreted as a positive cation, the Cl- in the urine will also increase to counteract this cation in the urine. This will be measured as an increase in urine chloride.

Thus, normal UAG response to metabolic acidosis is:
UAG = normal Na + Normal K+ - HIGH CL-
Urinary anion gap is VERY negative, reflecting high ammonia concentration.

-[NH4+] = UAG

35
Q

What does it mean if UAG is zero or positive in the presence of normal plasma anion gap metabolic acidosis?

A

It means ammonia is not being excreted properly -> distal tubule renal tubular acidosis

Type I renal tubular acidosis

36
Q

What is the urinary pH in Type I RTA and how does it change with plasma HCO3-? What pathophys mechanism accounts for this?

A

Distal renal tubular acidosis, associated with pH > 5.5 even with very low plasma [HCO3-], due to impaired ability to secrete H+ by alpha intercalated cells

  • > decreased titratable acid and trapping of NH4+ -> decreased net acid secretion
  • > impaired reabsorption of HCO3-, urine remains basic
37
Q

What type of carbonic anhydrase exists in the renal tubule lumen vs inside the cell?

A

Lumen - Carbonic anhydrase Type IV

Cell - Carbonic anhydrase Type II

38
Q

What are the causes of RTA Type I?

A

Congenital abnormalities:
Obstruction - damages collecting duct
Hereditary mutation in H+-ATPase

Drugs:
Amphotericin B, tenofovir -> nephrotoxic, increase H+ permeability, allowing diffusion of H+ back into the cell (urine cannot be acidified)

39
Q

What is RTA Type II? What will the urine characteristics be? Include pH and anion gap.

A

RTA Type II - proximal RTA
Impaired bicarbonate reabsorption in the proximal tubule leads to increased bicarbonate loss in urine

Urine pH will still be low (<5.5) as alpha-intercalated cells are functioning properly and can secrete H+ into urine via increasing ammonia production + increased H+ secretion.

UAG will be very negative (normal response to acidosis) since cells are responding properly

40
Q

What are the causes of Type II RTA?

A

Fanconi syndrome - proximal tubule transporters don’t work at all, leading to loss of all types of things in urine
-> caused by drugs like ifosfamide, cisplatin, tenofovir, expired tetracyclines

Carbonic anhydrase inhibitors - i.e. acetazolamide

Cystinosis

41
Q

What will happen to blood potassium levels in Type I and Type II RTA and why?

A

Type I - decreased ability to use H+/K+ antiporter inhibits K+ reabsorption -> hypokalemia

Type II - increased delivery of non-absorbable anions to principle cells -> increased negative luminal charge and K+ wasting -> hypokalemia

42
Q

What will a mutation in NBCe1 cause?

A

NBCe1 = sodium bicarbonate cotransporter -> Type II RTA

Less able to reabsorb bicarbonate on basolateral membrane of proximal tubule cell

43
Q

What will a mutation in AE1 cause?

A

Anion exchanger mutation on basolateral surface of alpha-intercalated cell (and proximal tubule, but failed distal acidification takes precedence)

-> Type I RTA

44
Q

What is the pathogenesis of Type IV RTA?

A

Hypoaldosteronism leads to hyperkalemia

Hyperkalemia causes impaired NH4+ generation by proximal tubule -> impaired excretion of acid
-> hyperkalemic renal tubular acidosis

45
Q

What is the definition of increased anion gap and what are the causes of increased anion gap metabolic acidosis?

A

Increased: Anion gap >12 mEq/L

MUDPILES
M: Methanol, metformin
U: Uremia
D: Diabetic ketoacidosis / ketoacidosis in general
P: Paracetamol - acetaminophen
I: Isoniazid, Iron tablets
L: Lactic acidosis
E: Ethylene glycol
S: Salicylates
46
Q

Why does uremia cause increased anion gap metabolic acidosis?

A

Associated with renal failure, which means decreased net acid excretion in general (urea formed from ammonia which was failed to be excreted) -> acidois

47
Q

Does metabolic acidosis happen early or late into salicylate overdose?

A

Late

Early you tend to see respiratory alkalosis due to stimulation of the respiratory centers

48
Q

Why is methanol ingestion toxic?

A

Step 1: Formaldehyde - toxic to optic nerve, causes blindness
Step 2: Formic acid (analagous to lactic acid of ethanol) - causes acidosis

49
Q

Why is ethylene glycol ingestion toxic?

A

Glycolic acid in metabolism - acidosis

Eventual formation of oxalic acid - precipitates as oxalate crystals in kidneys

50
Q

How does metformin cause problems with acid-base?

A

Can cause increased lactic acid production - lactic acidosis

51
Q

What is another name for normal anion gap metabolic acidosis? What causes it?

A

Hyperchloremic metabolic acidosis -> Cl- will rise to compensate for HCO3- loss.

-> due to loss of bicarbonate or addition of HCl

52
Q

What are the non-renal loss of HCO3- causes which induce a hyperchloremic metabolic acidosis?

A

Diarrhea - Rich in HCO3- and K+. Kidney will compensate well with acid secretion and K+ reabsorption.

Small bowel or pancreatic drainage - loss of HCO3- secretions

Ureterosigmoidostomy / malfunctioning ileal loop

53
Q

How does ureterosigmoidscopy lead to metabolic acidosis?

A

Urine is high in Cl-

After ureter cancer, you do this procedure, using a loop of bowel to connect bladder to urethra. Transporters in the bowel facilitate reabsorption of chloride with loss of bicarbonate.

54
Q

What is dilutional hyperchloremic acidosis? Where does this appear in the mnemonic for normal anion gap metabolic acidosis?

A

Rapid ECF expansion via NaCl will dilute out the current concentration of HCO3-, making the body relatively acidic

HARDASS
Hyperalimentation
Addison disease (hypoaldosteronism -> hyperkalemia -> acidosis)
Renal tubular acidosis
Diarrhea
Acetazolamide
Spironolactone - Type IV RTA
Saline infusion -
55
Q

What are situations where “HCl” could be added to induce hyperchloremic acidosis?

A

Parenteral nutrition - formulas contain excess cations -> arginine-Cl or lysine-Cl -> chloride rises and arginine / lysine are acid cations which need to be buffered

Eating HCl or NH4Cl -> ammonium chloride used to be used as a diet pill

56
Q

What are the three ways which you can cause a metabolic alkalosis?

A
  1. Excess loss of H+ from body
  2. Primary gain of HCO3-
  3. Loss of fluid containing Cl- in a concentration greater than ECF -> HCO3- was generated and left behind to create this fluid
57
Q

How does volume depletion “maintain” metabolic alkalosis?

A

Contraction alkalosis -> increase proximal Na reabsorption and associated HCO3- reclaimation.

Furthermore, aldosterone stimulates ENaC -> make lumen more negative -> increase H+ secretion -> reabsorption of HCO3- by alpha-intercalated cells

58
Q

Why does vomiting even doubly make for alkalosis?

A
  1. H+ lost -> HCO3- reabsorbed at basal surface
  2. Cl- loss (loss of concentrated chloride substance)
    - > sodium must be cotransported with HCO3- instead of Cl- to maintain euvolemia. -> more bicarbonate reabsorption.
59
Q

Why does increased HCO3- worsen alkalosis?

A

Increased HCO3- delivery to collecting duct -> non-reabsorbable anion -> secrete more K+ -> hypokalemia -> alkalosis due to stimulation of NH4+ production

60
Q

What is the formula for respiratory compensation of metabolic alkalosis? What is the limitation?

A

rise in pCO2 (hypoventilation) - limitation of hypoventilation is hypoxemia

Rise in pCO2 = 0.5 to 1.0 * rise in [HCO3-]

61
Q

What is the differential diagnosis of metabolic alkalosis based off of?

A

Based on urine [Cl-] -> low concentration of Cl- implies that bicarbonate is being reabsorbed largely because there is a deficit in Cl- to run Na/Cl- cotransporter -> HCO3- transporter goes in its place. -> kidney is focusing on ECF depletion, its #1 priority

62
Q

What are the two categories of metabolic alkalosis?

A
  1. Saline responsive: Urinary [Cl-] < 20 mEq/L
    - > ECF depletion is the issue
  2. Saline unresponsive: Urinary [Cl-] > 20 mEq/L
    - > ECF is normal or expanded
63
Q

What are two common causes of saline responsive metabolic alkalosis?

A

Diuretics, especially loop diuretics -> volume depletion, loss of chloride and sodium(NKCC)

Vomiting -> HCl loss, volume depletion

64
Q

What are two types of diarrhea which cause a metabolic alkalosis rather than metabolic acidosis?

A
  1. Villous adenoma -> secretes Cl- and K+ into bowels

2. Congenital chloride losing diarrhea

65
Q

How can hypercapnia predispose to alkalosis?

A

Long period of respiratory acidosis -> kidney stimulates HCO3- reabsorption

-> once intubated, HCO3- remains high, takes a couple days to correct

66
Q

What are the two usual broad causes of saline unresponsive metabolic alkalosis?

A

Excess mineralocorticoids -> K+ wasting, with increased acid secretion to reabsorb K+

Severe K+ depletion -> same reason as above

67
Q

What are the syndromes associated with excess mineralocorticoids?

A

Primary hyperaldosteronism
Cushing’s disease / syndrome - enough cortisol can overcome 11b-hydroxysteroid DH
Licorice ingestion - blockade of 11b-hydroxysteroid-DH

68
Q

What are the metabolic alkaloses causes where base is ingested faster than it can be excreted?

A

Excess alkali intake (baking soda) or milk-alkali syndrome

69
Q

Why does non-hyperparathyroid hypercalcemia cause metabolic alkalosis?

A

When bone is broken down, calcium carbonate is released. This is normally stimulated by PTH, whhich also signals to excrete bicarbonate in urine to prevent alkalosis.

If PTH is not accompanying the hypercalcemia, the release of bone bicarbonate will not accompany bicarbonate excretion -> alkalosis.

70
Q

What is the acute and chronic kidney compensation formula for changes in [HCO3-] with respiratory acidosis? What’s the max?

A

Acute: 1 mEq/L per 10 mmHg rise

Chronic: 3.5 mEq/L per 10 mmHg rise

Cannot rise above 35 mEq/L with compensation alone

71
Q

What is the acute and chronic kidney compensation formula for changes in [HCO3-] with respiratory alkalosis? What’s the min for each?

A

Acute: 2 mEq/L per 10 mmHg fall, but not less than 18

Chronic: 5 mEq/L per 10 mmHg fall, but not less than 14

72
Q

What is the system for approaching acid-base imbalances?

A
  1. Look at pH -> acidemia or alkalemia?
  2. Look at the directional change in HCO3- and pCO2 -> metabolic or respiratory issue? -> evaluate bicarbonate first
  3. Look at the amount of compensation -> if not appropriate, mixed disorder
  4. What is the underlying cause? -> calculate anion gap.

Look at urinary chloride if metabolic alkalosis
Calculate urinary anion gap if normal anion gap metabolic acidosis

73
Q

What is Winter’s formula for calculating bicarbonate compensation of metabolic acidosis?

A

Acceptable compensation:

pCO2 = 1.5 * [Bicarbonate] + 8 +/- 2

out of this range is a mixed disorder

74
Q

Can anion gap be increased in metabolic alkalosis?

A

Yes, absolutely. Despite the patient having an underlying metabolic alkalosis, they may also have an acidosis issue which is not large enough to cause acidemia.

75
Q

How can starvation increase the anion gap?

A

Increased ketone body production -> acids

Covered by MUDPILES mnemonic if the Diabetic ketoacidosis includes ketoacidosis of any kind (i.e. starvation-induced)

Pathophysiology - Urinary Tract (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions