An Introduction to Kidney and Body Fluids

Question 1

What are we made of? Overview of fluid compartments

compartments?
40-20 rule?

Answer 1

• The majority of the body is made up of water (60% of body weight)
this may vary with relative proportion of muscle and lipid
this means that in a 70kg body, 42 liters is water

The body water is distributed into two different water compartments

• intracellular fluid

• this contains 40% of the body weight
• in a 70 kg body, this is 28 liters of water

• extracellular fluid

• this contains 20% of the body weight
• in a 70 kg body, this is 14 liters of water
• > the extracellular fluid can be split into two
• interstitial fluid
• this contains 11 liters in a 70kg body
• plasma fluid
• this contains 3 liters in a 70kg body

• The figures mentioned above are fairly abstract as there are cells in the capillaries and in the blood plasma which contain water as well

Question 2

Body water and solutes

what is osmolarity?
are the solute composition the same? what must be kept the same?

what is the principal electrolyte of the ECF? what about ICF?

Answer 2

Osmolarity is the total concentration of osmotically active solutes

Solute composition of ECF and ICF differs, but osmolarity must be kept the same to avoid excessive shifts of water between ECF and ICF

Sodium is the principal electrolyte of the ECF, therefore sodium (with associated anions) is the major determinant of ECF osmolarity

K+ for intracellular fluid -> equal anion and cation

Question 3

Factors Important in Movement of Fluids Between

Compartments (2)

Answer 3

• Osmolarity

* Starling’s principle of fluid exchange

Question 4

Why is the control of body fluids important?

what needs to be controlled between compartments? why? what will happen if not controlled and issue with this?

what does there need to be adequate volume of? why?

Answer 4

• Cell volume

• the net movement of fluid between the compartments needs to be zero
• this is controlled by regulating the osmolarity of the fluids
• if there is a change in osmolarity, this will result in shift of fluid from one compartment to another
• large shifts between in ECFV and ICFV will disrupt tissue structure and function (through changes in the volume of the cell)
• regulation of extracellular osmolarity is important to ensure there are no large shifts between water in intracellular compartment and extracellular compartment
• > this is called osmoregulation

• Tissue perfusion

• this depends on the balance between circulating volume (plasma) and interstitial volume
• there has to be an adequate circulating volume in order to maintain blood pressure and thereby adequate perfusion of tissues
• if the ECF volume is lost, blood pressure will be lost, and therefore body tissues will be under-perfused

Question 5

Salt and water balance depends on two key processes

different regulations

Answer 5

Osmoregulation: maintain osmotic equilibrium between ICFV and ECFV

Volume regulation: maintain adequate ECFV to support plasma volume

Question 6

Dehydration

when does this happen?
what happens with volume of water and conc of Na+?
leads to?

major issue with this?

Answer 6

This happens when there is either decreased water intake or increased water loss or both

• When there is dehydration, the ECF water volume reduces while the solute concentration (Na+) remains constant
• This leads to an increase in osmolality of the ECF
• There is movement of water from the ICF to the ECF by osmosis thus causing a shrinkage of cells

• During dehydration, brain cells can shrink thus disrupting neural tissue and maybe also death

Question 7

Oedema

what is this?
why does it occur?
what could it be a consequence of?

what can cause a massive increase in ECF volume? what dpes this less to?

what happens if there is less perfusion in the kidney?

what happens if oedema in lungs?

Answer 7

Oedema is tissue swelling due to excess fluid in the interstitial space

• This happens when there is fluid imbalance between plasma space and the interstitial space
• It is a consequence of congestive heart failure
• it is the loss of heart function to be able to produce enough pressure to adequately perfuse all tissues
• there will be a massive increase in ECF volume from sodium and water retention
• there will be accumulation of fluid in the interstitial space

• there will be less perfusion in the kidney
- there will be less salt excretion which again will promote water retention thus making the problem bigger

• Oedema within the lungs can lead to serious pulmonary congestion and death

Question 8

Osmoregulation
calculating plasma osmolarity

equation?
what is the principle electrolyte?

Answer 8

Control of ECFV osmolarity in order to maintain osmotic equilibrium between ICFV and ECFV

Sodium (with its associated anions) is the principal electrolyte contributing to ECFV osmolarity

Plasma osmolarity can be estimated by:

2[Na] + 2[K] + [glucose] + [urea] (all in mmol L-1)

Typical:
2(135) + 2(4) + (5) + (5) = 288 mOsm L-1

2 because anions must have balance of cations

Question 9

Why is sodium important?

why not other ions?

Answer 9

So you can see why a percentage change in Na will have a bigger impact on osmolarity than any other electrolyte or solute.

Everything else (proteins, small molecules, other cations) is present in much lower concentrations and can be neglected as a contributor to osmolarity.

Question 10

Mechanism of osmoregulation

what are the 2 ways to chnage osmalarity of a solution?

how does the body achieve osmoregulation?
what happens when plasma osmolarity rises? falls?

Answer 10

There are two ways to change the osmolarity of a solution

1) Add/remove solute
2) Add/remove water

The body accomplishes osmoregulation by adding or removing water not sodium

• Plasma osmolarity rises – more water needed
  Kidneys respond by producing small volume of concentrated urine (water retention)
• Plasma osmolarity falls – too much water
  Kidneys respond by producing large volume of dilute urine (water excretion)

Question 11

Volume regulation

what detects the chnages in volume?
how is a fall in blood volume opposed?

Answer 11

Refers specifically to the control of the circulating (plasma) volume

Changes detected by stretch and pressure receptors in the cardiovascular system

A fall in blood volume is opposed by sodium retention; water follows osmotically, restoring volume

Note: although the total amount of body sodium may be increased, concentration (and hence osmolarity) is little changed because the retained sodium brings water with it

Question 12

The kidneys and the urinary tract

what is the kidneys function?
what is it by product?

Answer 12

Kidney function is homeostasis - The central function of the kidney is salt and water balance

The production of urine is a by-product of kidney function.

The urinary tract is important for temporary storage and then to remove the urine from the body

Question 13

Functions of kidney

8 different functions

Answer 13

• the production of urine is a central process of kidney function.

• the urinary tract is important for temporary storage and then to remove the urine from the body
• regulation of salt and water balance
• control of blood pressure
• regulation of electrolytes balance (eg potassium, calcium, phosphate)
• removal of metabolic waste products from blood
• removal of foreign chemicals in the blood (e.g. drugs)
• regulation of red blood cell production (erythropoietin)

Question 14

The nephron is the functional unit of the kidney

what is it?
what structures allow urine production to begin here?

Answer 14

• the nephron is the basic repeated unit of the kidney
• contains tiny tubes and interrelated blood capillaries

• urine production begins here with the help of many
structures:
- blood vessels, the glomerulus, bowman
capsule, the renal tubule

Question 15

The kidneys have a very strong vasculature

describe the vasculature
how it recieves blood? what it branches off to? what does this supply?
what drains the blood?

Answer 15

• each kidney receives blood via the renal artery
which subdivides until it branches down to
arterioles called afferent arterioles

• afferent arterioles supply the bowman capsule
of nephron

• there is an elaborate network of capillaries
associated with the tubule of the nephron

• the nephron is drained by a venule ultimatey
draining the kidney via the renal vein

Question 16

Nephrons are structurally organized in the kidney

describe the organisation of the nephon

what does the cortex contain?
what does the medulla contain?

Answer 16

• the nephron has a blind ending at one end
called the bowman capsule containing the
glomerulus which contains a series of curved tubules

• the tube continues down and comes back up again,
continues on and eventually drains into collecting ducts which come along to form the ureter

• the cortex of the kidney contains the bowman capsules and the tubules
• the tubules dip down to the medulla of the kidney

bowmans capsule -> glomerulus -> PCT -> thin loop of henle -> thick loop of henle -> DCT -> collecting duct -> ureter

Question 17

The four basic processes of renal function

Answer 17

Glomerular Filtration
Tubular Reabsorption
Tubular Secretion
Excretion of water and solutes in the urine

Question 18

glomerular filtration

where is blood filtered from the capillaries into the kidneys?

what drives this process? what causes an inward pressure?

which process is favoured and what does this lead to?

what is the glomerular filtration rate? what is it average to and % of renal flow?

when is this rate reduced?

what can be used as an index for the GFR? measured where and why is it produced? what does its conc depend on?

Answer 18

the blood is filtered from the capillaries into the kidneys at the bowman capsule
the entire blood volume is filtered out everyday several times
there are several forces that drive this filtration:

• > the capillary and bowman capsule are both lined up with endothelial cells
• hydrostatic pressure forces fluids and solutes through the glomerular capillary membrane
• here the small molecules pass readily into the bowman capsule whilst the larger proteins remain inside

-> this causes an inwards (towards the capillaries) osmotic pressure

the net gradient between the hydrostatic pressure and the osmotic pressure favors filtration
- thus the filtrate enters the bowman capsule

the glomerular filtration rate is monitored by doctors
- it is the amount of filtrate the kidneys produce each minute
- it averages to 125 ml/min (approx 20% of renal plasma flow) (6 liters/hour)
- the filtration rate is reduced in renal failure
- plasma creatinine levels can be used as an index to measure GFR
- it is easily measured in plasma
- produced as a byproduct of muscle metabolism at a
constant rate
- its concentration in the plasma will depend on the filtration rate

Question 19

Reabsorption

where does this take place? from where to where?
what will the filtrate from the earlier process contain? how much of solutes is reabsorbed?

when may glucose not be reabsorbed?

how does reabsroption take place? what can happen to water?

Answer 19

• this happens in the proximal region of the tubule
  many substances are filtered and then reabsorbed from the tubular lumen into the peritubular capillaries
• the filtrate from the earlier process (glomerular filtration) will contain virtually all the solutes of the blood except for the large proteins
• the important solutes now need to be reabsorbed
  180 liters of water is filtered each day but only 1.5 liters is excreted (rest is all reabsorbed)
  for mostly all the solutes, 99% of them are reabsorbed
• glucose may not be completely reabsorbed in pathological conditions such as diabetes and therefore there will be sugar in urine
• reabsorption takes place by active transport into the network of capillaries around the kidney tubules
• the epithelial cells around the kidney tubule will reabsorb many solutes which have been filtered into the kidney
• water can also be drawn back from the tubular fluid

Question 20

Secretion

importance of this? (4)

Answer 20

many substances are filtered and then reabsorbed from the tubular lumen into the peritubular capillaries during tubular reabsorption

tubular secretions are used for fine tuning and the secretion of additional solutes that need to be excreted

• this involves secretion of substances that were not filtered, or substances that were reabsorbed but need to be filtered
  this process also takes place in the peritubular capillaries
• > tubular secretion is important for:
• disposing of substances not already in the filtrate
• eliminating undesirable substances such as urea and uric acid
• ridding the body of excess potassium ions
• controlling blood pH

Question 21

Excretion of fluid and solutes in the urine

what 3 things determine what is excreted?
what is the eqaution

Answer 21

what is excreted depends on the amount filtered, the amount reabsorbed and the amount secreted

• the formula for total excretion = amount filtered - amount reabsorbed + amount secreted

Question 22

Control of Sodium and Water Balance

what controls body water and what controls body sodium

Answer 22

• Body water is controlled by osmoregulation
by controlling the osmolality of ECF

• Body sodium is controlled by volume regulation
by controlling the volume of water in the body

• Control is based on negative feedback systems

Question 23

Changes in water balance:

effect?

Answer 23

Changes in body fluid osmolality

Shift of water between ICFV and ECFV

Question 24

The Control of Water Balance

how is this done?

Answer 24

This is done by controlling the osmolality of the ECF
• Concentration or osmolarity can be changed in two ways
- change the amount of solute
- change the amount of water

• The body regulates osmolarity by changing the amount of water

• Controlling sodium is important in controlling the overall volume of water especially extracellular body water
- by retaining sodium, water is retained with it
- regulation of sodium is the defense of the circulating
volume

Question 25

A complex process occurs when there is a change in
amount of water in the body

what happens once there is a change in water?
what if there is an increase in water? decrease?
what will sense the change?
what is the response?
what is the net result?

Answer 25

• the change can be through water intake or excretion (water loss)
• there is a change in concentration of ECF fluid
- in the event of an increase in water intake osmolality goes down as there is the same concentration of solute and more water
- in the event of a decrease in water in the body, osmolality goes up as there is same concentration of solute and less water
• sensory neurons in the hypothalamus will respond to changes in interstitial fluid osmolality
• there will be a response in which a hormone is secreted by the pituitary which will act on the kidney changing the amount of water retained or excreted
• The total water in the body needs to be balanced
• input of water = output of water
• the balance needs to be 0 to maintain osmolality
• if there is a change in balance, it will change the body fluid osmolality
• this will result in transfer/shift of water between the ICF to the ECF

Question 26

The physiological response to water restriction

what will happen? what may this result in?
what detects thos?
what is released?
effect of this? (3)

Answer 26

• The physiological response to water restriction will follow the negative feedback system mentioned above
• the plasma osmolality will increase
• this may result in the moving out of ICF volume
• this will be detected by receptors in the hypothalamus
• there will now be increased secretion of the hormone called ADH/vasopressin
• increased vasopressin secretion will have several effects
- there will be a decrease in urine volume
- there will be an increase in urine osmolality
- the reabsorption of water in the kidney tubule will increase

Question 27

The physiological response to increase in water intake

what will happen? what may this result in?
what detects thos?
what is released?
effect of this? (3)

Answer 27

• The physiological response to increase in water intake will follow the negative feedback system mentioned above
• the plasma osmolality will fall
• this may result in the moving of ECF volume to the ICF volume
• this will be detected by receptors in the hypothalamus
• there will now be decreased secretion of the hormone called ADH/vasopressin
• decreased vasopressin secretion will have several effects
- there will be an increase in urine volume
- there will be a decrease in urine osmolality
- the reabsorption of water in the kidney tubule will decrease

Question 28

Plasma osmolality is maintained (~280 - 300 mOsmol/Kg) in face of changes in water intake
by retaining or by excreting water

what is max renal output and osmolality with excess water intake?

with restricted water intake?

Answer 28

• when there is an excess of water intake, the maximum renal output will be 20 liters a day and the osmolality will be less at 50mmol/liter
• when there is restricted water intake, the minimum renal output will be 0.5 liters a day and the osmolality will be high at 1200mmol/liter

• the above is accomplished by ADH systems, kidneys and the behavioral thirst response
- increase in interstitial fluid osmolality will result in brain mechanisms resulting in thirst

Question 29

Control of Sodium Balance

how is this done?
normal levels?
what is output?
why is Na+ balance important?
how is Na+ balance controlled?
what detecs the change?
what does it result in? via what 2 hormones?

Answer 29

• This is done by controlling the volume of water in the body
• Normal levels of Na+ concentrations is between 135 and 145 mmol/liter
• Total Na+ concentration in the body is input - output of Na+
• input can range from 10 to 400 mmol/day
• output involves loss in sweat, diarrhea, vomit and regulated renal excretion
• sodium balance is important as it is the major electrolyte of the ECF
• changes in Na+ concentration will lead to changes in ECF volume which will affect blood
volume and interstitial volume
• Na+ balance is controlled by a negative feedback system by the control of the ECF volume
• changes in Na+ concentration is detected by volume and pressure receptors
• this results in changes in renal sodium and excretion
• Two hormone systems control sodium balance (the primary function of these is volume
regulation)
• sodium retaining systems
- this is the renin-angiotensin-aldosterone system (RAAS)
• sodium eliminating pathways
- this is managed by cardiac natriuretic peptides
(ANP)

Question 30

The physiological response to increase in Na+ intake

what does increased sodium promote?
what detects this?
what is up-regulated and what is down-regulated? from where?
net effect?

Answer 30

• The physiological response to increase in Na+ intake
will follow the negative feedback system mentioned
above
• increase sodium intake will promote water retention
increasing ECF volume
• ANP will get up-regulated and RAAS will get downregulated
- the increase in ECF volume will be detected by
stretch receptors in the heart
- this will stimulate the release of ANP from the atria and down-regulate RAAS
• there will be a decrease in Na+ reabsorption and
therefore an increase in Na+ excretion

Question 31

The physiological response to decrease in Na+

what does decreased sodium promote?
what detects this?
what is up-regulated and what is down-regulated? from where?
what triggers sodiumd retention? 
net effect?

Answer 31

• The physiological response to decrease in Na+ will follow the negative feedback system mentioned above
• decrease sodium intake will decrease ECF volume
• RAAS will get up-regulated and ANP will get down-regulated
- reduced volume will mean a reduced perfusion pressure in the kidney
- this will be detected by sensory apparatus in the kidney
- this will result in increase in RAAS
- renin will be secreted by kidneys which will activate a circulatory precursor of angiotensin
- this will have various effects promoting increase in volume
- sodium retention will be triggered by aldosterone
• there will be an increase in Na+ reabsorption and therefore a decrease in Na+ excretion