Physiology Flashcards
What is osmolarity?
Concentration of osmotically active particles present in a solution.
Units osmol/l or mosmol/l.
What 2 factors are needed for osmolarity to be calculated?
The molar concentration of the solution.
The number of osmotically active particles present.
What is tonicity?
The effect a solution has on cell volume.
Define isotonic?
No change in cell volume as there is no net movement.
Define hypotonic?
More water outside the cell than inside the cell -> cell lysis.
Define hypertonic?
More water inside the cell than outside -> cell shrinkage.
How is distribution volume of a tracer measured?
Add a known quantity of tracer X (Qx) to the body.
Measure the equilibrium volume of X in the body ([X]).
Distribution volume (litres) = Qx/[X].
In what conditions does water intake need to increase to balance excessive water loss?
Hot weather.
Prolonged heavy exercise.
What are the main ions found in the ECF?
Na.
Cl.
HCO3 .
What are the main ions found in the ICF?
K.
Mg.
Negatively charged proteins.
Why are the osmotic concentrations of the ECF and ICF identical despite the cell membranes being selectively permeable?
Changes in solute concentrations lead to immediate changes in water distribution, the regulation of fluid balance and electrolyte balance are tightly intertwined.
If there are changes in salt concentration then it affects the osmolality between the inside and outside of the cell (osmotic imbalance).
This means water moves to try and maintain balance -> regulation of fluid balance and electrolyte balance are closely linked.
What is fluid shift?
Movement of water between the ICF and ECF in response to an osmotic gradient.
What would happen to the ECF and ICF volume if the osmotic concentration of the ECF increases?
Lose water and not salt so the ECF would become hypertonic compared to the inside of the cell.
Cell volume with decrease because its in a hypertonic solution so water is lost from inside the cell.
ICF volume decrease.
ECF volume increase.
What would happen to the ECF and ICF volume if the osmotic concentration of the ECF decreases?
The ECF becomes hypotonic as there is additional water in the ECF whilst salt remains the same.
This causes an osmotic gradient so water moves down the gradient to restore balance.
ICF volume increases.
ECF volume decreases.
What would happen to the ECF and ICF volume if there is NaCl gain in the ECF?
ECF volume increases.
ICF volume decreases.
What would happen to the ECF and ICF volume if there is NaCl loss in the ECF?
ECF volume decreases.
ICF volume increases.
Why is electrolyte balance important?
Total electrolyte concentrations can directly affect water balance (via changes in osmolarity).
The concentrations of individual electrolytes can affect cell function.
Na and K are major contributors to the osmotic concentrations of the ECF and ICF, respectively; they directly affect the functioning of cells
What can minor changes in ICF K concentrations cause?
Muscle weakness -> paralysis.
Cardiac irregularities -> cardiac arrest.
What are the functions of the kidney?
- Water balance.
- Salt balance.
- Maintenance of plasma volume.
- Maintenance of plasma osmolarity.
- Acid-base balance.
- Excretion of metabolic waste products (e.g. urea, bilirubin).
- Excretion of exogenous foreign compounds.
- Secretion of renin (control of arterial blood pressure).
- Secretion of erythropoietin (EPO; RBC production when hypoxic).
- Conversion of vitamin D into active form (Calcitriol: Ca2+ absorption in GI tract).
What is the primary function of the kidney?
Regulate the volume, composition and osmolarity of body fluids.
Controlled excretion of Na, K, H, Ca, Cl, PO4 and other substances.
What structures does the urinary system consist of?
Kidneys.
Ureter.
Bladder.
Urethra.
What is a nephron?
Functional unit of a kidney.
What are the functional mechanisms of a nephron?
Filtration.
Reabsorption.
Secretion.
What are the main differences between a juxtamedullary nephron and a cortical nephron?
Juxtamedullary: longer loop of Henle; single capillary (vasa recta) that follows the tubules; produces more concentrated urine than cortical nephron.
Cortical: shorter loop of Henle; meshwork of capillaries that follow the tubules.
What cells make renin?
The granular cells in the juxtaglomerular apparatus.
What is urine?
Modified filtrate of the blood.
Worth reviewing.
What are the filtration barriers in the kidney?
Glomerular capillary endothelium (barrier to RBC).
Basement membrane (basal lamina; plasma protein barrier).
Slit processes of podocytes (glomerular epithelium; plasma protein barrier).
Worth reviewing.
What is glomerular filtration rate?
The rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule per unit time.
How is GFR regulated extrinsically?
Sympathetic control via the baroreceptor reflex.
How is GFR regulated intrinsically?
Myogenic mechanism.
Tubuloglomerular feedback mechanism.
What is the relationship between arterial blood pressure and GFR?
Direct: increase in arterial BP => increase in GFR; decrease in arterial BP => decrease in GFR.
What is the myogenic mechanism of autoregulation in the kidney?
If vascular smooth muscle is stretched (i.e. arterial BP increases), it contracts thus constricting the arteriole.
The smooth muscle of the blood vessels reacts to the stretching of the muscle by opening ion channels, which cause the muscle to depolarize, leading to muscle contraction. This significantly reduces the volume of blood able to pass through the lumen, which reduces blood flow through the blood vessel. Alternatively, when the smooth muscle in the blood vessel relaxes, the ion channels close, resulting in vasodilation of the blood vessel; this increases the rate of flow through the lumen.
What is the tubuloglomerular feedback mechanism of autoregulation in the kidney?
If GFR rises transiently, more NaCl flows through the tubule leading to constricting of the afferent arterioles.
Involves the juxtaglomerular apparatus.
What is the juxtaglomerular apparatus?
The juxtaglomerular apparatus is a specialised structure formed by the distal convoluted tubule and the glomerular afferent arteriole. It is located near the vascular pole of the glomerulus and its main function is to regulate blood pressure and the filtration rate of the glomerulus.
Involves the macula densa cells which sense NaCl content of the tubular fluid, and granular cells (produce renin).
What is plasma clearance?
A measure of how effectively the kidneys can clean the blood of a substance.
Equals the volume of plasma completely cleared of a particular substance per minute.
Each substance that is handled by the kidney will have its own specific plasma clearance value.
What is suggestive of a substance being reabsorbed?
That its clearance is < GFR (determined by inulin or creatinine).
What is suggestive of a substance being secreted into the tubule?
If its clearance is > GFR (determined by inulin or creatinine).
What is suggestive of whether a substance is neither reabsorbed nor secreted?
If its clearance = GFR (determined by inulin or creatinine).
What are the key components for an ideal GFR marker?
Should be filtered freely and not secreted or reabsorbed.
How can renal plasma flow be calculated?
Using para-amino hippuric acid which is an exogenous organic anion.
What are the key components for an ideal renal plasma flow marker?
Should be filtered and completely secreted.
What is a filtration fraction?
The fraction of plasma flowing through the glomeruli that is filtered into the tubules.
I.e. ~20% of the plasma that enters the glomeruli is filtered. The remaining 80% moves on to the peritubular capillaries.
Where does reabsorption occur in the kidney?
Along the whole nephron but mainly in the proximal convoluted tubule.
What does the kidney reabsorb?
99% of fluid.
99% of salt.
100% of glucose.
100% of amino acids.
50% of urea.
0% of creatinine.
What is glomerular filtrate?
A modified filtrate of the blood (i.e. contains ions and solutes at plasma concentration but lacks RBCs and large plasma proteins).
What is the reabsorption rate in the proximal tubule?
About 80ml/min.
Flow rate at the start of the nephron is 125ml/min and decreases to 45ml/min when it reaches the Loop of Henle.
What is reabsorbed in the proximal tubule?
Sugars.
Amino acids.
Phosphate.
Sulphate.
Lactate.
What is secreted in the proximal tubule?
H+.
Hippurates.
Neurotransmitters (e.g. ACh, noradrenalin and adrenaline).
Bile pigments.
Uric acid.
Drugs (e.g. atropine, morphine, penicillin).
Toxins.
What are the steps that constitute transcellular tubular reabsorption?
A substance must pass through:
- Apical/luminal membrane.
- Cytoplasm.
- Basolateral membrane.
- Lateral space.
- Peritubular capillary.
How can substances be reabsorbed in the tubule?
Transcellular.
Paracellular.
What are the types of carrier-mediated membrane transport?
Primary active transport.
Secondary active transport.
Facilitated diffusion.
What is primary active transport?
Energy is directly required to operate the carrier and move the substrate against its concentration gradient.
E.g. Na+/K+ ATPase pump.
Movement up a concentration gradient.
What is secondary active transport?
The carrier molecule is transported coupled to the concentration gradient of an ion (usually Na+).
E.g. symporters, antiporters.
Movement down a concentration gradient.
What is facilitated diffusion?
Passive carrier-mediated transport of a substance down its concentration gradient.
Movement down an existing concentration gradient of a substrate.
What types of transport are going on in this diagram of examples?
Why is an energy-dependent Na-K ATPase transport mechanism at the basolateral membrane essential for Na reabsorption?
It maintains a low concentration of Na inside the cell which is necessary for the cells function.
As sodium-glucose co-transporter, sodium-amino acids co-transporter and a countertransporter bring Na ions from the tubular fluid into the cell, meaning the Na-K ATPase pump moves Na actively out of the cell into the peritubular plasma for them to reach the blood.
Why is iso-osmotic fluid reabsorbed across ‘leaky’ proximal tubular epithelium and why does the osmolarity of the fluid not change?
Due to standing osmotic gradient and oncotic pressure gradients.
Salt and water are reabsorbed in equal proportions.
What helps pull salt and water from the interstitial fluid into the peritubular plasma in the proximal tubule?
Plasma proteins in the peritubular plasma create an osmotic drag for water and chloride to be pulled through.
How is glucose reabsorbed in the proximal tubule?
The sodium-glucose co-transporter moves glucose from the interstitial space into the cell.
Then glucose is moved from the cell into the peritubular space by facilitated diffusion at the basolateral membrane.
Water follows the movement of glucose across this osmotic gradient.
What is the transport maximum?
The point at which increases in the concentration of a substance (filtration) do not result in an increase in movement of a substance across a cell membrane (reabsorption), hence that substance is then excreted.
- Red line represents how much glucose is being filtered per minute (rate of filtration depends upon plasma concentration of that particular substance x GFR).*
- Black line represents rate at which glucose is being reabsorbed by the kidney - it matches the red line up until a point where it plateaus. Anything that is not reabsorbed is then secreted (blue line).*
- Normally all filtered glucose is being reabsorbed as it is below the renal threshold of 10-12mmol/L; if it goes above that then it is saturated and glucose is excreted.*
What drives sodium reabsorption in the proximal tubule?
The basolateral Na+-K+ ATPase pump.
What drives Cl- ion reabsorption in the proximal tubule?
Na+ reabsorption drives Cl- ion reabsorption through the paracellular pathway.
How does fluid flow in the loop of Henle?
Opposing flow in the two limbs is termed countercurrent flow ( fluid flows down the descending limb and up the ascending limb).
The entire loop functions as a countercurrent multiplier.
Together the loop and vasa recta establish a hyper-osmotic medullary interstitial fluid.
What happens in the ascending loop of Henle?
Along the entire length, Na and Cl are reabsorbed (achieved by active transport in the thicker (higher) part of the limb and by passive in the thinner (lower) part of the limb).
This limb is relatively impermeable to water meaning little or no water follows salt reabsorption.
What happens in the descending loop of Henle?
This segment does not reabsorb NaCl and is highly permeable to water.
How are Na and Cl reabsorbed in the thick ascending limb of the loop of Henle, whilst it is impermeable to water?
The tight junctions are particularly tight so that water cannot follow the salt that is being actively transported by the triple co-transporter into the loop of Henle and then on into the interstitial fluid.
How is NaCl absorbed from the cell of the thick ascending loop of Henle into the interstitial fluid?
Through recycling of K+ from being transported into the cell by the triple co-transporter and by the Na-K ATPase pump and then diffused out of the cell.
What happens to the osmolarity of the fluid passing through the loop of Henle and why?
- Solute removed from the lumen of ascending limb (water cannot follow).
- Tubular fluid is diluted and osmolality of interstitial fluid is raised.
- Interstitial solute cannot enter the descending limb.
- Water leaves the descending limb by osmosis.
- Fluid in the descending limb is concentrated.
How is the cortico-medullary concentration gradient reached in the loop of Henle?
- Solute pumped out of the ascending limb.
- The osmolality of the interstitial fluid rises.
- Passive water efflux from the descending limb.
- Flow occurs moving everything on as before.
Essential blood flow through the medulla tends to wash away NaCl and urea.
What minimises this problem?
- Vasa recta capillaries follow hairpin loops.
- Vasa recta capillaries are freely permeable to NaCl and water.
- Blood flow to vasa recta is low (few juxtamedullary nephrons).
What receptor does ADH bind to and where?
Vasopressin type 2 on the basolateral membrane of cells in the distal tubule and collecting duct.
What effect does vasopressin have on distal tubule and collecting duct cells?
Increases permeability of the luminal membrane to water by inserting aquaporins.
What happens to the fluid in the distal tubule in the presence of maximal ADH plasma concentrations?
Tubular fluid equilibrates with interstitium via aquaporins to reabsorb water and concentrate the tubular fluid.
What happens to the fluid in the collecting duct in the presence of minimal ADH plasma concentrations?
The collecting duct and distal tubule cells are relatively impermeant to water, so there is no water reabsorption.
What is the effect of ADH on urine osmolarity, volume and total solute excretion?
ADH has no influence on salt reabsorption by the tubular cells.
Worth reviewing.
What happens if there are abnormal increases in the renin-angiontensin-aldosterone system?
Hypertension.
Fluid retention associated with congestive heart failure.
- Treatment = low salt diet, diuretics (loop).*
- ACE inhibitors will stop fluid and salt retention and arteriolar constriction.*
Worth reviewing.
Worth reviewing.
Worth reviewing.
H+ ion secretion is what is driving the new bicarbonate formation.
How do certain respiratory conditions generate respiratory acidosis?
How does the kidney compensate for respiratory acidosis?
H+ secretion is stimulated.
All filtered HCO3- is reabsorbed (so none is excreted).
H+ continues to be secreted and generates titratable acid and NH4+.
Acid is excreted and ‘new’ HCO3- is added to the blood causing plasma bicarbonate concentrations to rise as a result of respiratory acidosis and as a result of renal compensation.
Correction requires lowering CO2 partial pressure by restoration of normal ventilation.
How do certain conditions generate respiratory alkalosis?
How does the kidney compensate for respiratory alkalosis?
Blood CO2 partial pressure is what drives H+ secretion by the kidney, so excessive removal of CO2 reduces H+ secretion into the tubule.
The H+ secretion is insufficient to reabsorb the filtered HCO3-, even though the load is lower than normal, so HCO3- is excreted and urine is alkaline.
No titratable acid and NH4+ is formed, so no “new” HCO3- is generated.
Renal compensation further lowers plasma concentrations of HCO3-.
Correction requires the restoration of normal ventilation.
How does the respiratory system compensate for metabolic acidosis?
How is metabolic acidosis corrected?
Filtered HCO3- is very low and very readily reabsorbed.
H+ secretion continues and produces titratable acid & NH4+ to generate more “new” HCO3-.
The acid load is excreted (urine is acidic) and plasma HCO3- is restored.
Ventilation can then be normalised.
Acid load cannot be excreted immediately, therefore, respiratory compensation is essential.
How does the respiratory system compensate for metabolic alkalosis?
How is metabolic alkalosis corrected?
Filtered HCO3- load is so large compared to normal that not all of the filtered HCO3- is reabsorbed which depends upon the plasma concentration times the GFR (i.e. since concentration is higher than normal, more is filtered).
No titratable acid or NH4+ is generated.
HCO3- is excreted (urine is alkaline).
Plasma bicarbonate ion concentration falls back towards normal.
