Physiology Flashcards
What is osmolarity
Concentration of osmotically active particles present in a solution
How do you calculate osmolarity
Molar concentration of the solution x number of osmotically active particles
E.g. 150mM NaCl
150 x 2 = 300 mosmol/l
What is tonicity
Effect a solution has on cell volume
3 types of tonicity
Isotonic
Hypotonic
Hypertonic
Hypotonic solution effect on cell
Water moves into cell
Hypertonic solution effect on cell
Water moves out of cell
Isotonic solution effect on cell
No change in cell volume
Tonicity is dependent on
Osmolarity
Ability of solutions to cross the cell membrane
Total body water is made of what compartments
Intracellular fluid + Extracellular fluid
Extracellular fluid includes
Mostly interstitial fluid
plasma
Lymph
Transcellular fluid
How do you measure the body fluid compartments
Use tracers
For TBW = 3H20
For ECF = Inulin
For plasma = labelled albumin
Water loss occurs at
Skin
Lungs
Sweat
Faeces
Urine
Hot weather causes increase / decrease in water loss from lungs
Decrease
Hot weather causes increase / decrease in water loss from urine
Decrease (since more is lost in sweat; decreased excretion of urine is a compensatory mechanism)
How is water balance achieved when there is extra water loss due to exercise / hot weather / cold weather
Increased water ingestion
Decreased excretion of water by kidneys to a certain extent, not sufficient alone
Describe the characteristics of ionic composition of ICF and ECF
There is always more Na+, Cl-, HCO3- in ECF than ICF
There is always more K+ in ICF than ECF
Why is regulation of ECF volume essential
Because it contain plasma so regulation of ECF is required for regulation of blood pressure
Gain in NaCl in ECF causes
Osmolarity of ECF to increase
Causes fluid to move from ICF into ECF
ICF decreases
= fluid homeostasis
Na+ is mainly present in which body fluid compartment
What does this imply for the compartment
ECF
So it is a major determinant of ECF volume
K+ plays a key role in
Establishing membrane potential
K+ is mainly in which body fluid compartment
ICF
Functions of the kidney
Regulate volume, osmolarity, composition of body fluids
Excretion of waste produces and exogenous foreign compounds (drugs / additives)
Secretion of renin
Secretion of erythropoietin
Conversion of vitamin D into active form
Functional unit of kidneys
Nephron
General function of nephron
Filter out tubular fluid
Reabsorb substances from the fluid or secrete substances into the tubular fluid
Vessels in nephron
Afferent arteriole -> Glomerulus -> efferent arteriole -> peritubular capillaries -> venule -> vein
What is Glomerulus
Cluster of blood vessels located in bowman’s capsule where filtering of the blood occurs
What is the bowman’s capsule
where waste in blood is filtered out of glomerular capillaries and enters the lumen of bowman’s capsule which then enter the Proximal tubule
Bowman’s capsule is made of what cells
Podocytes
Which are the 3 filtration barriers
Capillary endothelium
Basal lamina
Podocytes
Why can’t proteins enter the glomerular filtrate
Net negative charge of basal lamina repel the proteins
Too big to go through the pores of endothelium
Except from capillary endothelial cells, the glomerulus also contains
Mesangial cells
Function of mesangial cells
control glomerular filtration
provide structural support
How do mesangial cells control glomerular filtration
Mesangial cells can contract which narrows the capillary lumen hence less flow of blood = less filtration
Location of mesangial cells
intercapillary space
Between the afferent and efferent arterioles
2 types of nephron
Juxtamedullary
Cortical
Which type of nephron is predominant in humans
Cortical nephron (80%)
Differences between juxtamedullary and cortical nephron
Juxtamedullary nephron has longer loop of Henle
Juxtamedullary nephron does not have peritubular capillaries, it has 1 capillary called vasa recta
Route of vasa recta
Follows the loop of Henle
The diameter of afferent arteriole is larger / smaller than efferent arteriole
Larger
Renin is secreted by
Granular cells
4 parts of the nephron
Renal corpuscle
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Renal corpuscle consists of
Glomerulus and Bowman’s capsule
Function of Renal corpuscle
Production and collection of glomerular filtrate
Function of proximal convoluted tubule
Reabsorption of water, amino acids, glucose
Function of loop of Henle
Creation of hyper osmotic environment in medulla
Function of distal convoluted tubule
Absorption of water, Na+, bicarbonate, K+ and H+
for acid-base and water balance
What proportion of sodium is reabsorbed in proximal tubule and through which mechanism
70% by active transport
What proportion of glucose and amino acids is reabsorbed in proximal tubule and through which mechanism
All glucose and amino acids; by co-transport
What feature do the lining of proximal convoluted tubule have to increase reabsorption
Microvilli
Histological differences between proximal and distal convoluted tubules
PCT larger
PCT less well defined lumen margin due to microvilli
How does the thickness of loop of henle vary
Descending limb - first thick then thin limbs
Ascending limb - thick limb
Type of epithelial cell that lines the loop of Henley
thick limbs (ascending and descending limbs) - simple cuboidal
thin limbs (descending limb) - simple squamous
Is there microvilli in distal convoluted tubule
No, very sparse apical microvilli
Reabsorption of Na+ hence water in DCT is controlled by which hormone
Aldosterone
Reabsorption of water in collecting duct is controlled by which hormone
ADH
How does ADH increase water reabsorption in collecting duct
Increase aquaporin channels
The epithelium of minor, major calyxes, ureter, bladder and urethra
Urothelium
Urothelium type of epithelium
transitional epithelium
What is transitional epithelium
= properties lie between stratified squamous and simple non-stratified
What are the cells of urothelium that is facing the lumen called
Umbrella cells
Special properties of umbrella cells and why
thickened and inflexible membrane, to provide a highly impermeable barrier
Layers below the urothelium (from inner to outer)
Connective tissue
Smooth muscle
Adventitia
Serosa
The smooth muscle in urinary bladder is called
Detrusor muscle
Function of detrusor muscle
Contract to
- push urine out of bladder
- prevent back flow of semen during ejaculation
- prevent back flow of urine into ureter
Pressures that are included in the net filtration pressure for glomerular filtration
Bowman’s capsule fluid pressure
Glomerular capillary blood pressure
Capillary oncotic pressure
Bowman’s capsule oncotic pressure
Which pressure is the key driver of glomerular filtration
Glomerular capillary blood pressure
Pressures that pushes plasma through the filtration barriers
Glomerular capillary blood pressure
Bowman’s capsule oncotic pressure ( but 0 mmHg)
Pressures that draws fluid away from bowman’s capsule
Bowman’s capsule hydrostatic pressure
Capillary oncotic pressure
What is capillary oncotic pressure
Due to presence of plasma proteins = higher osmolarity than filtration fluid hence wants to draw fluid back into vessel
Why is bowman’s capsule oncotic pressure 0 mmHg
because there is no plasma proteins in filtration fluid hence no oncotic pressure that will try to draw water in
Normal net filtration pressure
10 mmHg
GFR =
filtration coefficient x net filtration pressure
Filtration coefficient can change depending on
how permeable the glomerular membrane is
Why is glomerular capillary blood pressure constant throughout
Because the afferent arteriole has a wider diameter than efferent arteriole
What happens to GFR when there is an increase in arterial BP
Increase in arteriole BP -> increase in BP in afferent arteriole -> increase in Glomerular capillary BP -> increase in net filtration pressure -> increase in GFR
What happens to urine volume when there is an increase in GFR
Increases
Changes in systemic arterial BP does not necessarily result in changes in GFR. Why is that
Due to auto regulation, compensatory mechanisms ; but only to a certain extent
what are the 2 mechanisms of auto regulation to prevent changes in GFR
Myogenic
Tubuloglomerular feedback
What is the myogenic auto regulation of GFR
Increase in BP causes vascular smooth muscle to stretch -> causes constricting of arteriole -> less blood flowing through to glomerulus
What is the tubuloglomerular autoregulation of GFR
- Rise in GFR
- more NaCl flow through the tubule
- constriction of afferent arterioles
Tubuloglomerular auto regulation involves which type of nephron
Juxtaglomerular
Effect of kidney stones in GFR
Stone blocking fluid causing fluid to accumulate -> Increases bowman’s capsule fluid pressure -> lower net filtration pressure -> GFR decrease
Effect of diarrhoea in GFR
diarrhoea causes dehydration causing higher osmolarity in blood
so increase in capillary oncotic pressure
hence draws more fluid out
reduces net filtration pressure
= decrease in GFR
What is plasma clearance
measures how effectively kidneys can clean the blood of a substance
each substance will have their own specific plasma clearance
What is plasma clearance
measures how effectively kidneys can clean the blood of a substance
each substance will have their own specific plasma clearance
Plasma clearance =
rate of excretion of X / plasma concentration of X
Rate of excretion of X =
[X in urine] x Urine production rate
What is used to measure the GFR
Inulin clearance = GFR
Why is inulin used to measure GFR
Because it is freely filtered at glomerulus but it is not absorbed / metabolised hence can be measured in urine
If clearance < GFR
Substance is reabsorbed into the tubule
If clearance = GFR
Neither reabsorbed nor secreted
If clearance > GFR
Substance is secreted into tubule
If clearance > GFR
Substance is secreted into tubule
What is reabsorption
water and solutes within the tubule are transported into the bloodstream
Around how much plasma entering the glomerulus is being filtered
20%; 80% of the plasma is not filtered and leaves via efferent arteriole
Kidneys reabsorb what % of fluid and salt
99%
Kidneys reabsorb what % of glucose and amino acids
100%
Kidneys reabsorb what % of creatinine
0%
What is reabsorbed in the proximal tubule
67% of all salt and water
100% of glucose and amino acids
Phosphate
Sulphate
Lactate
What is secreted in the proximal tubule
H+
Neurotransmitters
Bile pigements
Uric acid
Drugs
Toxins
2 routes reabsorption takes place
transcellular ( through cells)
paracellular ( between cells)
How does transcellular reabsorption occur
Primary active transport
Secondary active transport
Facilitated diffusion
How is Na+ reabsorbed back into capillary
- Basolateral sodium potassium ATPase transports K+ into the tubular cell in exchange for sodium out of the cell = reabsorbed
- This creates a concentration gradient for Na+ between the filtrate and tubular cell
- So sodium in the filtrate enters the tubular cell via facilitated diffusion (and this sodium will later be transported out via sodium potassium ATPase)
- Reabsorption of Na+ sets up an electrochemical gradient that drives the passive movement of Cl- via the paracellular route
Describe the paracellular route of Cl-
- Cl- moves passively into the interstitial fluid (between tubular cell and capillary) via paracellular route due to electrochemical gradient set up by Na+
- forms NaCl
- NaCl reabsorbed
- Sets up a osmotic gradient that drives passive movement of water via the paracellular route
- Because the water movement is dependent on NaCl, their reabsorption are equal
- so no change in osmolarity in filtrate fluid
Why is the filtrate in proximal tubule isosmotic
Because the reabsorption of NaCl and water is equal
Na+ is reabsorbed everywhere in the nephron except
descending limb of loop of henle
What is transport maximum
maximum rate at which we can reabsorb a particular substance
What determines the limit for transport maximum
saturation of the specific transport systems of substance = i.e. if more substances come in, they cannot be reabsorbed
Why is transport maximum important in relation with glucose
Glucose transport maximum is 375mg/min; exceeding this = glucose in urine
What is renal threshold
the concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine. - this can be reabsorbed depending on the transport maximum
Renal threshold and transport maximum varies between substances. Why is it beneficial for renal threshold to be lower than transport maximum for certain substances - glucose / amino acids
This means that some glucose/ amino acids will be in the urine but because transport maximum is higher, all of those substances can be reabsorbed up to a certain extent
Function of loop of Henle
Generates a cortico-medullary solute concentration gradient
in order to form hypertonic urine
Describe the flow of fluid in loop of Henle
Countercurrent flow - the flow of fluid in both limbs are opposing each other
Why is there an osmotic gradient in the medulla
Due to difference in permeability of water and salt for descending and ascending limbs
Describe the permeability to water and NaCl for descending and ascending loops of henle
Descending - permeable to water, not to NaCl
Ascending - impermeable to water, NaCl can be reabsorbed
Mechanism of sodium reabsorption in ascending loop of Henle
via Na K Cl transporter (triple transporter)
The reabsorption of water in descending limb of loop of Henle uses
Countercurrent flow mechanism
Describe the countercurrent flow mechanism
- Na+ and Cl− are actively pumped out of the filtrate in ascending limb
- Water does not follow because it is impermeable to water
- This causes the osmolarity of the interstitial fluid to be raised
- Water moves out of the descending limb by osmosis
- But Solute cannot enter the descending limb
- Because water is moving out of DL, osmolarity of fluid in DL is raised while the interstitial fluid is lowered
- concentrated fluid in DL then moves into AL, process begins again
What drugs blocks the triple transporter in ascending limb and why
Loop diuretics
So less Na+ reabsorbed = increased excretion of water (less water reabsorbed from descending loop) = decreased blood pressure
Osmolarity of fluid leaving the ascending loop of Henle
Hypotonic (low osmolarity)
What structure is involved in countercurrent exchange
Vasa recta
Describe the countercurrent exchange mechanism
As the concentrated fluid flows next to the vasa recta, the electrolytes and water that have been reabsorbed from the filtrate diffuse out of the fluid and into the blood vessels
What property of vasa recta allows countercurrent exchange mechanism to work
It is freely permeable to water and NaCl
Blood flow to vasa recta is slow
Describe the change in blood osmolarity in vasa recta
Rises as it goes down into the medulla - because solute is reabsorbed from the concentrated interstitial fluid
Decreases as it rises back up into the cortex - because water in interstitial fluid is reabsorbed
Slow blood flow in vasa recta allows
maintains the solute concentration gradient in the medulla
because solute that is reabsorbed into blood can go back out into the interstitial fluid
Effect of low ADH
- collecting ducts in the kidney remain relatively impermeable to water
- This means that water cannot be effectively reabsorbed
- Since the urine is not concentrated in the collecting ducts, there is no significant driving force to draw water out of the descending limb
- = weak concentration gradient in medulla
- = large amount of diluted urine
