Introduction to renal function Flashcards
What are the functions of the kidney?
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)
What is the extracellular space?
interstitial space and
intravascular space
Describe the distribution of water weight
o 2/3 = intracellular
o 1/3 = extracellular (15L)
2/3 is extravascular
1/3 is intravascular
How is volume determined?
osmotic (oncotic) forces
How do particles cross a permeable membrane?
particles will move freely and even out the concentration on either side
How do particles cross a semi-permeable membrane?
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
What happens when you increase osmolality in the interstitial space?
water will move out of the cells
How is volume determined?
hydrostatic and osmotic (oncotic) forces
How is Hydrostatic pressure determined?
generated by heart pumping and the vessels squeezing
Where has greater oncotic pressure?
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
Where has higher hydrostatic pressure?
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
What is the composition of the extracellular fluid?
mostly NaCl
o Some contribution from K, Ca, bicarbonate
What is the composition of intracellular fluid
mostly K/bicarbonate/proteins
o Also phosphate and sulphate
What is the effect of 1L water administration on body fluid compartments
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
What is the effect of 300 mmol of sodium (NaCl) administration on body fluid compartments
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
What is the effect of 300 mmol of sodium with 1L water (isotonic fluid) administration on body fluid compartments
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
What are the three basic processes of the kidney?
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
Describe the glomerular filtration barrier
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
What is the normal GFR?
approximately 100ml/min = 144L per day
o Varies depending on a lot of aspects
o Younger people tend to have a higher GFR
Describe fluid reabsorption
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
Describe the distal tubule
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
Describe tubular reabsorption
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
Why is varying the concentration of urine important?
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.
Describe the ‘rules’ of the loop
- Thick ascending limb is impermeable to water, but actively transports sodium, potassium and chloride
- Thick ascending limb provides the concentration gradient to promote water reabsorption from thin DLH
- Thin descending limb is freely permeable to salt and water
- Vasa recta doesn’t wash away the gradient because they use countercurrent exchange makes it more
efficient. Loop makes the process much more efficient
Describe the interaction between the kidney and the circulation
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
What is the function of the juxta-glomerular apparatus?
maintains GFR in face of increases or decreases in blood flow to the kidney
How does the juxta-glomerular apparatus maintain GFR?
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
What is the kidneys response to reduced sensed volume?
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)
How does olguria present?
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
What are Natriuretic peptides and why are they produced?
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
