Renal Regulation Of Water And Acid-base Balance Flashcards by Callum Reeson

Calculation for osmolarity?

Concentration x no. Of dissociated particles
= Osm/L or mOsm/L

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What is the relationship between osmotic pressure and the no. Of solute particles?

Directly proportional

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Calculate the osmolarity for 100 mmol/L glucose and 100mmol/L NaCl.

Osmolarity for glucose = 100 x 1 = 100 mOsm/L
Osmolarity for NaCl = 100 x 2 = 200 mOsm/L

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What percentage of body weight is made up by total fluid volume?

Around 60%

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What proportion of total fluid volume sits in the ECF compared to intracellular?

1/3 extracellular, 2/3 intracellular

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What are the different ways in which water is lost via an unregulated mechanism?

Sweat, feces, vomit, water evaporation from respiratory lining and skin

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What are the two mechanisms of renal regulation of water loss ?

Positive water balance
Negative water balance

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Outline the mechanism of renal regulation of a positive water balance

High water intake -> inc. ECF volume, dec. conc. of sodium, dec. osmolarity -> hypo-osomtic urine production -> osmolarity normalizes

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Outline the mechanism of renal regulation of negative water balance

Lower water intake -> dec. ECF volume, inc. conc. of sodium, inc. osmolarity -> hyperosmotic urine production -> osmolarity normalises

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For water reabsorption to occur from the loop of henle and collecting duct does the medullary interstitium need to be hyper or hypoosomtic?

Hyperomsotic since water is reabsorbed through the passive process of osmosis

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What are the two steps of countercurrent multiplication?

Active salt reabsorption
Passive water reabsorption

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What occurs during the active salt reabsorption stage of countercurrent multiplication?

Salt actively pumped out of thick ascending limb of loop of henle

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What occurs during the passive water reabsorption step of countercurrent multiplication?

Water passively reabsorbed from thin ascending limb of loop of Henle

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What are the two main objectives of urea recycling?

Have urea concentrated in interstitium to inc osmolarity for passive water reabsorption
Loss of urea with least amount of water lost

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What are the two pathways for urea once it has left the collecting duct?

Enters blood circulation via vasa rectum or enters back into the nephron through thin descending limb

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How does urea enter the thin descending loop of Henle?

Through UT-A2 receptors

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Outline the affect of vasopressin on urea recycling?

Boosts UT-A1 and UT-A3 numbers

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T or F NaCl and urea are both responsible for generating a hyperosmotic medullary interstitium?

True

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What is the main function of ADH?

Promote water reabsorption from collecting duct

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Where is ADH produced?

Hypothalamus - supraoptic and paraventricular nuclei

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Where is ADH stored?

Posterior pituitary

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What factors stimulate ADH production?

Inc. plasma osmolarity
Hypovolemia
Dec. Blood pressure
Nausea
Angiotensin 2
Nicotine

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What factors inhibit ADH production?

Dec. Plasma osmolarity
Hypervolemia
Inc. blood pressure
Ethanol
Atrial natriuretic peptide

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What percentage change in blood pressure is required for baroreceptors to signal to inc/dec ADH production?

5-10%

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What does diuresis describe?

Increased dilute urine excretion

In diuresis what is the level of ADH?

Low or zero

Following diuresis is the urine hyper/ hyposomolar?

Hypo-osmolar

What does anti- diuresis describe?

Concentrated urine in low volume excretion

List three examples of ADH-related clinical disorders

Central diabetes insipidus Syndrome of inappropriate ADH secretion (SIADH) Nephrogenic diabetes insipidus

What are the causes of central diabetes insipidus?

decreased/ negligent production and release of ADH

What are the clinical features associated with central diabetes insipidus?

Polyuria and polydipsia

Treatment options for central diabetes insipidus?

External ADH

Causes of syndrome of inappropriate ADH secretion (SIADH)?

Increased production and release of ADH

What are the clinical features associated with SIADH?

Hyperosmolar urine Hypervolemia Hyponatremia

What is Hypervolemia?

Too much fluid volume in the body

Treatment for SIADH?

Non-peptide inhibitor of ADH receptor

What are two examples of non-peptide inhibitors of ADH receptors given to treat SIADH?

Conivaptan and tolvaptan

causes of nephrogenic diabetes insipidus?

Less/ mutant AQP2 Mutant V2 receptor

What are the clinical features associated with nephrogenic diabetes insipidus?

Polyuria and polydipsia

Treatment options for nephrogenic diabetes insipidus?

Thiazide diuretics and NSAIDS

What are the three roles of the kidney in regulation of acid-base balance?

Secretion & excretion of H+ •Reabsorption of HCO3- •Production of new HCO3-

Henderson-hassalbach equation: what effect does an inc. in concentration of bicarbonate have on conc. of H+ ?

decrease

What percentage of bicarbonate ions are reabsorbed in the kidneys?

100%

What are the two ways in which new bicarbonate ions are produced in the kidneys?

Through the proximal convoluted tubule Through distal convoluted tubule and collecting duct

Outline the process of new bicarbonate ion production by the proximal convuluted tubule

ammoniogenesis: glutamine produces 2 ammonium ions and 2 bicarb. ammonium ions must be excreted to allow for net addition of bicarb.

Outline the process of bicarbonate ion reabsorption through the distal convuluted tubule and collecting duct?

Alpha-intercalated cells: HCO3- reabsorption and H+ secretion Beta-intercalated cells: HCO3- secretion and H+ reabsorption

EXPECTED RANGES FOR PH, CO2, HCO3

pH= 7.4 HCO3- = 24mEq/L PCO2 = 40mmHg

How much water is absorbed in the PCT?

67%

During the active salt reabsorption stage of counter current multiplication, what happens to the osmolarity of the interstitium?

Increases, resulting in the passive reabsorption of water

Per countercurrent multiplication, what happens to new filtrate as it arrives in the nephron?

Salt is actively pumped out producing the gradient which helps the passive reabsorption of water

Outline the mechanism of urea recycling What affect does this have?

Filtrate arrives at collecting duct UT-A1 on apical membrane UT-A1 on basolateral membrane Urea pumped out into medullary interstitium Urea reabsorbed by thin descending loop of Henle by UT-A2 receptors Or reabsorbed by vasa recta (UT-B1) Increases osmolarity of interstitium

Release of ADH has what affect open UT-A1 and UT-A3 receptors? What is the effect of this>?

Increases no. Of receptors Increases permeability of collecting duct to urea

T or F: ADH regulates the no. Of aquaporin Channels in both the apical and basolateral membranes of the principal cells

True

T or F: The blood of someone with SIADH will slowly get more hyperosmotic?

False

T or F: NaCl and urea are both responsible for generating a hyperosmotic medullary interstitium?

True

T or F: one of the body’s response to inc, plasma osmolarity is the trigger of thirst?

True

T or F: Intravenous fluid infusion first enters the intracellular fluid and then travels to the ECF compartment?

False

T or F: osmolarity for 100mmol/L NaCl is less than 200mmol/L NA+ ions?

False

Outline the mechanism of action of ADH

Mechanism of ADH • ADH arrives a principal cell • binds to the V2 receptor and activates G protein cascade • results in activation of PKA • PKA increases APQ2 vesicle migration to apical cell membrane • water reabsorption increases • ADH up/downgrades AQP2 & AQP3 numbers as required

Outline the mechanism of diuresis:

Mechanism of diuresis • AP2 is absent on DCT due to lack of ADH • tubular fluid is hyposmotic due to active salt reabsorption • little water reabsorption occurs

In what ways does ADH support sodium reabsorption? TAL,DCT,CD

Increases transporters Thick ascending limb: inc. Na/K/Cl symporters DCT: inc. Na/Cl symporter CD: inc. sodium channels

Do beta-intercalated cells produce HCO3- into the tubular fluid or into the blood?

Tubular fluid

When alpha-intercalated cells of the DCT and collecting duct secrete H+ into the tubular fluid, what reaction occurs?

Binds with bicarbonate -> H2CO3 -> H20 + CO2

Where in the nephron are alpha and beta intercalated cells found?

The distal convuluted tubule and the collecting duct

How does bicarbonate reabsorption occur in the proximal convuluted tubule?

Carbonic anhydrase produces H+ and HCO3-, HCO3- leaves via Na+ symporter

What is the Henderson- hassalbach equation and what is it used for?

Used to determine pH from HCO3- and CO2 pH = pK + log HCO3-/aPCO2

What causes respiratory acid base disorders?what causes metabolic acid base disorders>

Resp= CO2 Metabolic = HCO3-

How is normal acid base balance maintained?

Diet and metabolism adds both acid and base to the body Base excreted in faeces Net addition of metabolic acid to the body which must be neutralised This is achieved by bicarbonates leading to production of sodium salts and strong acids and CO2 These are excreted by the kidneys and the lungs

Outline the process of new bicarbonate production in the proximal convuluted tubule

Ammoniogenesis: glutamine produces 2 ammonium ions and 2 bicarbonate ions Ammonium ions must be excreted to allow net addition of HCO3-

In the process of new bicarbonate ion production via the PCT, how are ammonium ions excreted?

Via Na+/H+ antiporters Via diffusion in the form of NH3 gas

Outline the process of new bicarbonate ion production in the DCT and CD?

Protons neutralised by urinary buffer e.g. phosphate Bicarbonate from CO2 is effectively a new ion

How much bicarbonate is absorbed along the different parts of the nephron?>

80% in PCT 10% in loop of Henle (ascending limb) 6% in DCT 4% in collecting duct

A low HCO3- and low pH describes what acid base imbalance?

Metabolic acidosis

A high HCO3- and pH are characteristic of what type of acid base imbalance?

Metabolic alkalosis

A high PCO2 and low pH suggest which type of acid base imbalance?

Respiratory acidosis

A low PCO2 and low pH are suggestive of what acid base imbalance?

Respiratory acidosis

What is the compensatory mechanism for metabolic acidosis?

Inc. ventilation to inc bicarbonate reabsorption and production

What is the compensatory mechanism for metabolic alkalosis?

Dec. Ventilation resulting in increased bicarbonate excretion

What is the acute compensatory response for respiratory acidosis?

Intracellular buffering

What is the chronic compensatory response for respiratory acidosis?

Increased bicarbonate reabsorption and production

What is the acute compensatory mechanism for respiratory alkalosis?

Intracellular buffering

What is the chronic compensatory response for respiratory alkalosis?

Decreased bicarbonate reabsorption and production

Identify the acid base disorder: pH =7.2, HCO3- = 17, PCO2 =35

Metabolic acidosis

Define osmolarity

Osmolarity is a measure of the solute (particle) concentration in a solution (osmoles/liter)

What is the normal plasma range for osmolarity?

275-295mosmoles/L

Why does a high salt diet lead to an increase in blood pressure?

Increased salt in the diet leads to increased total body sodium so water is taken in to maintain osmolarity and this increases ECF fluid volume. This increases the pressure in the system i.e. increased blood pressure.