Introduction to renal function

Question 1

What are the functions of the kidney?

Answer 1

 Overall function: maintain homeostasis  with urine as a by-product
 Removing metabolic waste from the extracellular fluid (urea, acids)
 Controlling the volume of extracellular fluid (close link to blood pressure)
 Maintaining optimal concentrations of vital solutes in the extracellular fluid (Na, K, H, Ca, Mg, Cl, Phos)

Question 2

What is the extracellular space?

Answer 2

interstitial space and

intravascular space

Question 3

Describe the distribution of water weight

Answer 3

o 2/3 = intracellular
o 1/3 = extracellular (15L)
 2/3 is extravascular
 1/3 is intravascular

Question 4

How is volume determined?

Answer 4

osmotic (oncotic) forces

Question 5

How do particles cross a permeable membrane?

Answer 5

particles will move freely and even out the concentration on either side

Question 6

How do particles cross a semi-permeable membrane?

Answer 6

particles stay on one side, generating
a force for water movement
o These differences are generated by protein pumps,
particularly Na-K- ATPase
o Cell proteins even out the osmotic pressure  results in even
osmotic pressure on either side

Question 7

What happens when you increase osmolality in the interstitial space?

Answer 7

water will move out of the cells

Question 8

How is volume determined?

Answer 8

hydrostatic and osmotic (oncotic) forces

Question 9

How is Hydrostatic pressure determined?

Answer 9

generated by heart pumping and the vessels squeezing

Question 10

Where has greater oncotic pressure?

Answer 10

Intravascular space has a greater oncotic pressure than outside the vascular space
o Generated mainly by intravascular plasma proteins that don’t cross the vascular barrier

Pressures reversed (although not equally compared to the arterial side) at the venous end
o Oncotic pressure driving fluid in is not as great at the
hydrostatic pressure that drove it out on the arterial end
o Lymphatic system compensates for extra fluid

Question 11

Where has higher hydrostatic pressure?

Answer 11

higher at the arterial end, drives fluid out at the arterial end

Pressures reversed (although not equally compared to the arterial side) at the venous end
o Oncotic pressure driving fluid in is not as great at the
hydrostatic pressure that drove it out on the arterial end
o Lymphatic system compensates for extra fluid

Question 12

What is the composition of the extracellular fluid?

Answer 12

mostly NaCl

o Some contribution from K, Ca, bicarbonate

Question 13

What is the composition of intracellular fluid

Answer 13

mostly K/bicarbonate/proteins

o Also phosphate and sulphate

Question 14

What is the effect of 1L water administration on body fluid compartments

Answer 14

 Number of particles (osmoles) does not change
 Volumes will change very slightly (in proportion to the size of the compartment)
 Water distributes evenly across the three compartments because of osmosis

Question 15

What is the effect of 300 mmol of sodium (NaCl) administration on body fluid compartments

Answer 15

 Number of particles has increased, but volume hasn’t
 Particles will only be distributed across the extracellular compartment
 When Na enters cells, it is pumped back out by Na-K- ATPase
 This means that the number of particles will increase in:
o Intravascular space
o Extravascular space
 Won’t increase in the intravascular space
 This generates an osmotic potential, and water moves out of the cells into the extracellular space
o The volume in the EC space will increase

Question 16

What is the effect of 300 mmol of sodium with 1L water (isotonic fluid) administration on body fluid compartments

Answer 16

 Increase the number of particles in the EC space
 Increase volume of fluid in the EC space
 None of the water enters the IC space to maintain osmolality

Question 17

What are the three basic processes of the kidney?

Answer 17

 Glomerular Filtration: Filtering of blood into
tubule forming the primitive urine (glomerular
filtrate)
 Tubular Reabsorption: Selective absorption of
substances from tubule to blood
 Tubular Secretion: Secretion of substances from
blood to tubular fluid

Question 18

Describe the glomerular filtration barrier

Answer 18

 Size-selective sieve
 A unique structure allowing extracellular fluid to be filtered and to leave the body
 Specialised capillary endothelium => not found anywhere else in the body
o Fenestrations between endothelial cells
 Glomerular basement membrane - collagen based
 Podocyte foot processes => provide a large surface area and gaps for filtrate to pass through

Question 19

What is the normal GFR?

Answer 19

approximately 100ml/min = 144L per day
o Varies depending on a lot of aspects
o Younger people tend to have a higher GFR

Question 20

Describe fluid reabsorption

Answer 20

 Reabsorption of fluid is driven mainly by Na-K- ATPase on basolateral surface of cells
 Drives a concentration gradient for sodium within the cell
 Open channels for sodium on the apical (luminal) surface of the cell
 Sodium tends to travel with an anion (usually Cl - )
 This drives an osmotic gradient for water reabsorption
 Process requires a lot of energy
 To maximise efficiency:
o Lots of mitochondria lined up alongside energy-requiring channels
o Large surface area => brush border on luminal edge of cell

Question 21

Describe the distal tubule

Answer 21

 Principle cell => gradient driven by Na-K- ATPase creates a concentration gradient for sodium uptake by
ENAC
o ENAC => sodium travels into the cells and then interstitium, bringing water with it
> Exchanged for potassium => mechanism for K + excretion

 Intercalated cell
o Negative charge created by the movement of sodium into the cells also creates a mechanism for H + excretion
> Na-K- 2Cl (NKCC) channel
o gradient driven by Na-K- ATPase creates a concentration gradient for sodium uptake
o sodium moves accompanied by 2Cl and K
o This creates a positive excess of K in the cell
o K leaks back out through K channel
o Creates a positive charge in the lumen => allows paracellular reabsorption of Ca and Mg

Question 22

Describe tubular reabsorption

Answer 22

 Approximately 70% sodium chloride is reabsorbed in proximal tubule.
 Nearly all amino acids and glucose are reabsorbed in proximal tubule
 Some acid secretion in proximal tubule
 Distal tubule => fine tuning, excretion of H/K
 Loop of henle/collecting duct => varying urine concentration

Question 23

Why is varying the concentration of urine important?

Answer 23

 Crucial to survival on land
 If no system for concentrating urine relative to plasma then no way of dealing with salt/water depletion.
 If no system for diluting urine relative to plasma then no way of dealing with water excess.

Question 24

Describe the ‘rules’ of the loop

Answer 24

1. Thick ascending limb is impermeable to water, but actively transports sodium, potassium and chloride
2. Thick ascending limb provides the concentration gradient to promote water reabsorption from thin DLH
3. Thin descending limb is freely permeable to salt and water
4. Vasa recta doesn’t wash away the gradient because they use countercurrent exchange  makes it more
   efficient. Loop makes the process much more efficient

Question 25

Describe the interaction between the kidney and the circulation

Answer 25

 Circulation has baroreceptors to detect PRESSURE (not volume!)
 Signal to the brain to increase sympathetic activity if low pressure is detected
o Causes constriction of afferent arteriole to protect kidney function
o Reduces blood supply to the kidney => reduces filtration and therefore excretion

Question 26

What is the function of the juxta-glomerular apparatus?

Answer 26

maintains GFR in face of increases or decreases in blood flow to the kidney

Question 27

How does the juxta-glomerular apparatus maintain GFR?

Answer 27

 Distal tubule reflects closely to glomerulus and afferent/efferent arterioles
 Contains specialised epithelium
o Macula densa – senses tubular flow
 Increased tubular flow  Macula densa produces adenosine  causes afferent arteriolar constriction
 Reduced tubular flow (reduced sensed volume)  sensed by macula densa
o Granular cells are stimulated to produce renin
o Results in RAAS pathway
o ANG II  causes vasoconstriction of the efferent arteriole
 This increases glomerular filtration pressure  preserves glomerular filtration even
though the blood flow to the kidneys has decreased
 Increases reabsorption of sodium in proximal tubule (and therefore water)
 Stimulates production of aldosterone by the adrenal gland
 Increases reabsorption of NaCl through ENAC and K + excretion

Question 28

What is the kidneys response to reduced sensed volume?

Answer 28

 Efferent glomerular arteriolar constriction preserves waste
excretion
o Increases filtration pressure in the glomerulus
 Avid tubular sodium and water re-absorption preserves
extracellular fluid volume
 NET EFFECT – OLIGURIA (<0.5ml/kg/hr)

Question 29

How does olguria present?

Answer 29

o Reduced urine volume => more tubular filtrate reabsorbed
o concentrated urine (i.e. high osmoles/kg urine)
o Low urine sodium concentration (<20mmol/L)
o High urine potassium secretion because of the effect of aldosterone on the distal tubule

Oliguria is a common emergency
o Not always bad, but shows the body is under stress and that the kidney is working at its maximum to maintain homeostasis

Question 30

What are Natriuretic peptides and why are they produced?

Answer 30

Natriuretic peptides produced in response to increased sensed volume oppose effects of angiotensin II
on kidney – ‘Pressure natriuresis’
o ANP – atrial natriuretic peptide
o BNP – brain natriuretic peptide
 Kidney increases excretion of NaCl in response to these signals from the circulation