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NancyPHARM205 > Tut2: Water Balance > Flashcards

Tut2: Water Balance Flashcards

Have not added in what the different drugs do at different sections of the nephron.

1
Q

What are the eight functions of the kidney?

A

Remove waste products from body

Regulate plasma volume

Regulate plasma osmolarity

Regulate blood pressure

Regulate acid base balance and electrolytes

Produce erythropoietin

Synthesise enzymes required for vit D activation from skin/diet

Major route if elimination for a large number of water soluble drugs

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2
Q

How does the kidney regulate plasma volume

A

primarily altering excretion of sodium in the urine

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3
Q

How does the kidney regulate plasma osmolarity

A

Primarily by altering the excretion of water in the urine

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4
Q

How does the kidney regulate blood pressure

A

By regulation of plasma volume

By production of renin secreted in response to renal hypoxia

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5
Q

How does the kidney regulate acid base balance and electrolytes?

A

By altering excretion of H+ and HCO3- ions in the urine

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6
Q

Describe the Renin Angiotensin Aldosterone System

A

-Some change causes a decrease in renal perfusion pressure.
- this is detected by the juxtoglomerular apparatus in the kidney
- kidney releases renin
- renin reacts with angiotensinogen released from liver to produce angiotensin1
- angiotensin converting enzyme released from pulmonary and renal endothelium converts angiotensin1 to angiotensin2
- angiotensin 2 :
Increases SNA
Increases tubular Na+ and Cl- reabsorption and K+ excretion and H2O retention
Increases blood pressure by arteriolar vasoconstriction
Increases ADH secretion from posterior pituitary this causes water reabsorption from the collecting duct

And causes aldosterone secretion from adrenal medulla

  • aldosterone also increases tubular Na+, Cl- reabsorption and K+ excretion and water retention
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7
Q

What turns off the RAAS?

A

RAAS causes Water and salt retention

Effective circulating volume will increase

This causes perfusion pressure of juxtoglomerular apparatus to increase to normal

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8
Q

What two components make up the kidney?

A

Vascular component and tubular component

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9
Q

Where does filtration take place?

A

In the glomerulus (vascular cmponent)

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10
Q

What is blood delivered by?

A

Afferent arterioles

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11
Q

Where does the blood go after leaving the afferents arterioles?

A

It goes to the glomerulus > efferent arterioles > capillaries which turn reabsorbed substances from tubular to the vascular component

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12
Q

How much filtrate is processed by the kidneys each day?

A

180L

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13
Q

How much of this filtrate is reabsorbed back into the vascular component?

A

99%

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14
Q

How is the movement of substances out of the tubule facilitated?

A

By the structure of the tubuel

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15
Q

Why do the kidneys need to produce a wide range of urine concentration and volumes?

A

Salt and water intake in the diet vary widely, so kidneys must produce a wide range of Urine concentration and volumes for the body to remain in water balance.

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16
Q

What is the most dilute urine

A

50mosmol/L

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17
Q

What is the most concentrated urine

A

1200mosmol/L

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18
Q

What is plasma osmolarity?

A

290mosmol/L

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19
Q

What is the osmolarity of the renal cortex?

A

300 mosmol and it does not change

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20
Q

What is the osmolarity of the outer medulla?

A

400-600mosmol

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21
Q

What is the osmolarity of the inner medulla?

A

800-1200mosmol

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22
Q

Where is the loop of henle 1200 mosmol?

A

At the bottom of the descending loop of henle

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23
Q

What happens when plasma osmolarity is reduced?

A

Circulating ADH decreases. This causes less water to be reabsorbed so more is excreted in the urine .

This decreases plasma volume, so plasma osmolarity will increase

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24
Q

What happens when the body is dehydrated?

A

Circulating ADH will be high .
This will cause more aqua porins to be inserted in the ascending loop of henle and the collecting duct so less water is excreted in the urine.

This will retain water, and increase plasma volume

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25
Q

What is urine specific gravity?

A

A measure of the density of urine compared with the density of water

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26
Q

What is the normal range of urine specific gravity?

A

1.002-1.040

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27
Q

What can urine specific gravity be used to estimate?

A

Urine osmolarity

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28
Q

In most cases, what does urine specific gravity increase linearly with?

A

Increasing urine osmolarity

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29
Q

How is urine generated?.

A

Via three processes:
Glomerular filtration,
Tubular reabsorption
Tubular secretion

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30
Q

Where do the three processes of urine formation take place?

A

In the nephrons

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31
Q

What is filtration.

A

The movement of fluid and solutes from the glomerular capillaries into the Bowman’s capsule

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32
Q

What is reabsorption ?

A

The movement of filtered substances out of the tubule and into the surrounding peritubular capillaries

This takes place throughout the nephron

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33
Q

What is secretion?

A

The movement of selected unfiltered substances from the peritubular capillaries into the renal tubule for excretion

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34
Q

What is in the urine?

A

Any substance that is filtered or secreted but not absorbed

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35
Q

What is osmolality

A

The measure of the attractiveness of water to a particular particle

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36
Q

What does serum osmolality measure?

A

The amount of solutes dissolved in the serum

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37
Q

What are the chemicals that affect osmolality.

A

Na+, Cl-, HCO3-, proteins and glucose

38
Q

What is osmolality defined as?

A

The number of osmoles of solute per kg of solvent

Expressed in terms of osmol/kg or osm/kg

39
Q

What is osmosis?

A

The diffusion of water through a semi-permeable membrane from an area of high to low solute concentration

40
Q

What are the two homeostatic mechanisms that work together to control plasma osmolality and hence body water content?

A

Thirst and ADH system

41
Q

What are these homeostatic mechanisms stimulated by?

A

Change in plasma osmolarity

42
Q

Where is this stimulus which activates the thirst and ADH system detected?

A

In receptors in the supraventricular nuclei in the hypothalamus

There is no blood brain barrier here so neurons are exposed directly to changes in blood osmolarity

43
Q

What does an increase in osmolarity result in?

A

Water leaving the cell, this decreases cell volume

This results in sensation of thirst and release of ADH

44
Q

What does a decrease in osmolarity result in?

A

Water entering the cell which increases cell volume

This will suppress thirst and inhibit the release of adh

45
Q

What happens if the body fluids are hyperosmotic?

A

This means body fluid has high concentration of particles. i.e. high osmolarity.

Circulation of ADH is high

Insertion of water channels into apical membranes of cells lining the collecting ducts occurs

Water is reabsorbed and retained by the body.

This increases plasma volume, decreasing plasma osmolarity

46
Q

What happens when body fluids are hypoosmotic?

A

This means body fluids have less osmolarity .

This causes circulating ADH to be reduced or absent

This causes water channels to be removed from the collecting duct

Any excess water is excreted in the urine

47
Q

How much of cardiac output do kidneys receive?

A

20%

48
Q

What does renal blood flow auto regulation chiefly depend on?

A

A combination of:

Pre-glomerular arteriolar vasodilation and

Post glomerular arteriolar vasoconstriction

49
Q

What is pre glomerular arteriolar vasodilation mediated by?

A

Prostaglandins and nitric oxide

50
Q

What is post glomerular arteriolar vasoconstriction mediated by?

A

Angiotensin II

51
Q

What are prostaglandins?

A

Potent vasodilators important for maintaining blood flow to the glomerulus and medulla

Especially in conditions that cause decreased perfusion of blood to the kidneys

E.g. In hypotension

52
Q

What are some factors which affect blood supply to the kidneys?

A

Situations where CO is compromised

Drugs which affect action of prostaglandins or angiotensin II

Direct injury

Ischaemia (atherosclerosis)

Tumour causing renal artery obstruction

53
Q

What does the rapidity which the thirst response can contribute to restoration of plasma osmolarity depend on?

A

The rate at which fluid is absorbed from the gut

54
Q

What does this rate of which fluid is absorbed by the gut depend on?

A

The rate of gastric emptying and

The osmolarity of the fluid

55
Q

What happens when you drink a more concentrated fluid than the blood? (HYPERTONIC)

A

Initially water will be removed from the body into the intestinal lumen

Water will then be reabsorbed secondary to solute absorption

56
Q

What does rapid emptying and dilute solution allow?

A

Rapid absorption

57
Q

How is water absorbed from a hypertonic solution?

A

It is delivered to the intestine

It then enters the portal, then systemic circulation

Plasma osmolarity falls, ADH release is inhibited

Existing circulating ADH disappears over 15-30mins
AQP are removed from collecting ducts

Rate of urine excretion rises and urine specific gravity falls,
The urine excreted will be dilute, and have a low urine osmolarity.

58
Q

What happens once a hyperosmotic fluid reaches the intestine?

A

The osmotic gradient may first draw water from the extracellular compartment into the gut lumen

59
Q

Glucose is rapidly absorbed. What follows?

A

Water follows.

It goes into the portal circulation, to the liver

60
Q

Glucose is removed by the liver. What happens to the water?

A

Water is handled by the kidneys as a hypo-osmotic solution

61
Q

Then plasma osmolarity decreases, what does this trigger?

A

ADH decreases,

AQP removed from apical membrane

excess water is excreted by kidney in the urine

62
Q

What happens if an isoosmotic solution enters the stomach?

A

No absorption occurs as solution is isoosmotic with blood

63
Q

The Na+ from the isoosmotic solution is absorbed from the intestine. What follows?

A

Water and Cl- follow passively

Absorbed fluid enters portal then systemic circulation

Extracellular volume is expanded but plasma osmolarity is unchanged

64
Q

What effects does an isoosmotic solution have in ADH?

A

ADH is not stimulated and circulating levels of it a relatively unchanged

There are no major changes in urine output

65
Q

If you were working within a community pharmacy and a friend of a patient with dehydration secondary to food poisoning was asking your advice, what oral rehydration would you recommend? Why?

A

Isoosmotic solution.

It does not change plasma osmolarity, but will change plasma volume, so will treat the dehydration and cause body to retain more water as ADH circulation will remain unchanged.

66
Q

What does MSU test for, what is the reference data?

A

PH 4.5-8

Proteins <10 white cells/cmm

67
Q

What is MSU ?

A

Mid stream urine

68
Q

What is MSU used for?

A

A simple diagnostic test, usually for UTI/kidney infection

69
Q

What can MSU tell us?

A

Evaluate causes of kidney failure

Screen for chronic diseases like diabetes mellitus and hypertension

70
Q

When is urine infection generally diagnosed.

A

Based in results of urineanalysis -

Urine culture is often ordered as a follow up test to identify bacteria that may be causing infection

71
Q

What is GFR?

A

The volume of plasma filtered across the glomerulus per unit of time

It is the sum of filtration rate from each functioning nephron

72
Q

What directly correlates with GFR?

A

Renal function,

I.e. the processes of filtration, secretion and reabsorption, endocrine and metabolic functions of the kidney

73
Q

Why is plasma creative an ideal endogenous substance for measuring the GFR?

A

It is freely filtered at the glomerulus but is not reabsorbed

74
Q

What is the normal reference range for creatinine in adult males? In adult females?

A 
Males = 60-150umol/L 
Females= 49-90umol/L
75
Q

What is the ideal method for calculating CrCl levels ?

A

By performing a collection of urine over 24 hours and taking a plasma sample midway through this period

However it is difficult and inconvenient to undertake accurately in practice

76
Q

Why is serum creatine not a good marker of renal function?

A

It is influenced by age, gender, ethnicity, muscle mass

77
Q

It is much accurate account for these variables. How is this done?

A

These variables are accounted for by a formula which works out the creatine clearance as an estimation of GFR

78
Q

What is the most widely used formulae for predicting GFR?

A

Cockcroft-Gault equation

This has been validated for dose adjustment in renal impairment.

CrCl= (Fx (140-age) x weight) / (SrCl (umol/L)) 
Weight = lean body weight in kg
F = 1.04 in females, 1.23 for males

Male IBW= 50kg + (0.9x every cm over 150cm in height)
Female IBW= 45kg + (0.9 x every cm over 150cm in height)

79
Q

What are some limitations of the Cockcroft Gault equation?

A

It is not validated in some populations

It is unreliable in extremes of body sizes (severe malnutrition/obesity)

It is imprecise and unreliable for rapidly changing renal function e.g. (ICU, ARF)

It tends to overestimate renal function at lower levels particularly in obese or fluid overloaded patients.

We use the ideal body weight calculations to overcome this.

80
Q

What problems can arise when giving drugs to patients with reduced renal function?

A

Reduced renal excretion of drug or its metabolises may cause toxicity

Sensitivity to some drugs is increased even if elimination is unimpaired

Many side effects are tolerated poorly by patients with renal impairment

Some drugs are not effective when renal function is reduced

81
Q

How can problems arising due to giving drugs to those with reduced renal function be avoided?

A

By reducing the dose of the drug

By giving an alternative drug

82
Q

What kind of drugs act at the proximal convoluted tubule?

A

Acetazolamides

83
Q

Which drugs act in the ascending loop of henle?

A

Bumetanide, furosemide, torsemide, ethacrynic acid

84
Q

Which drugs act at the distal convoluted tubule?

A

Thiazides

85
Q

Which drugs act in the collecting duct?

A

Spironolactone, amiloride, triamterene

86
Q

What are Acetazolamides?

A

Act in the proximal convoluted tubule
- Carbonic anhydrase inhibitor which inhibits reabosprtion of HCO3-

  • Weak diuretic properties
87
Q

What do Bumetanide, Furosemide, Torsemide and Ethacrynic acids do?

A

Acts in Ascending loop of henle.
-Inhibits Na+/K+/Cl- co-transporter resulting in retention of Na+, Cl- and Water retention in the tubule

Most efficacious of the diuretics

88
Q

What do Thiazides do?

A

Act in the distal convoluted tubule
- To inhibit reabsoprtion of Na+ and Cl- resulting in retention of water
Most commonly used diuretics

89
Q

What do Spironolactone, Amiloride, Triamterenes do?

A

Act in the collecting duct
-Spironolactone is an aldosterone antagonist and inhibits the aldosterone mediated reabsorption of Na+ and secretion of K+

  • Amiloride & trimterene block Na+ channels
  • These drugs prevent hypokalemia which occurs with thiazide or loop diuretics
90
Q

How does renal function affect BP and fluid balance?

A

Regulation of ECF important in long term regulation of BP

  • Increased Plasma volume –> Increased BP
  • Decreased plasma volume –> Decreased BP

Plasma volume regulated primarily by altering the EXCRETION of SODIUM in the urine

NancyPHARM205 (15 decks)

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