Physiology II Flashcards
What is the two solute hypothesis
Concentration of urea in the kidney is dependent on the concentration gradient created by active transport of NaCl
The presence of these 2 solutes allows kidney to concentrate urea in the urine and excrete it
How does urea contribute to the cortico-medullary concentration gradient
- The ascending limb of loop of Henle actively transports out NaCl without water
- Water is drawn out of the descending limb of loop of Henle without solute moving
- The concentration gradient in medulla established by NaCl draws water out of the collecting duct which dips into the medulla
- This makes the tubular fluid in collecting duct concentrated with urea
- Hence urea moves out of the collecting duct to interstitial fluid -> reabsorbed back into the ascending limb -> contribute to the concentration of urine
The distal tubule and collecting duct are major sites for
regulation of ion and water balance
Distal tubule and collecting duct ability to regulate ion and water balance can be affected by
ADH
Aldosterone
PTH
Atrial natriuretic hormone (ANP)
What factor allows the production of hypertonic urine in presence of ADH
Cortico-medullary concentration gradient
How does the cortico-medullary concentration gradient allow the production of hypertonic urine in presence of ADH
- The function of ascending and descending limbs of loop of Henle creates a highly concentrated interstitial fluid in medulla
- The tubular fluid flowing into the collecting duct is less concentrated because NaCl was pumped out to contribute to the gradient
- Collecting duct had low permeability to water but in presence of ADH, it becomes more permeable
- Water can then flow from collecting duct into the interstitial fluid to be reabsorbed due to the osmotic gradient established by the countercurrent flow
Function of ADH
Increase water reabsorption to decrease plasma osmolarity
Function of aldosterone
Increase Na+ reabsorption
Increase K+ secretion (so less K+ in blood; this is why hyperaldosteronism causes high BP and hypokalaemia)
Function of ANP
Decrease Na+ reabsorption
Function of PTH
Increase Ca2+ reabsorption
Decrease phosphate reabsorption
Distal tubule is in the cortex / medulla
Cortex
Osmolarity of the fluid entering distal tubule
Hypoosomtic
Describe the permeability of distal tubule
Low to water and urea
But can be affected by ADH
Low permeability to urea in distal tubule means that
Tubular fluid is concentrated with urea
Early distal tubule function
NaCl reabsorption using Na K Cl transporter (triple transporter)
Late distal tubule function
Reabsorption of
Ca2+
Na+
K+
Secretion of H+ and aldosterone
How does aldosterone alter the late distal tubule function
Instead of reabsorbing K+, aldosterone will cause the secretion of K+ into tubular fluid -> excreted
The collecting tubule is located at
Going down from cortex to medulla
Describe the interstitial fluid around medulla
Progressively increasing concentration (osmolarity)
Late collecting duct function
Low ion, water, urea permeability
But can be influenced by ADH
Triggers of ADH release
Increase in plasma osmolarity
Decrease in blood pressure
Nicotine
What inhibits ADH release
Alcohol
How does drastic decrease in blood volume (trauma) cause ADH secretion
Decrease in blood volume -> decrease in blood pressure -> decreased atrial pressure activates left atrial stretch receptors -> stimulates ADH release
How does ADH decrease plasma osmolarity
Increase aquaporin channels on the collecting duct
Increase thirst -> increase H2O intake
Effect of ADH on urine
Small, concentrated (hypertonic) urine
Triggers of aldosterone release
Increase in K+ plasma concentration
RAAS
90% of K+ is reabsorbed in
proximal tubule
10% in distal tubule
Is there K+ urine
No, all are reabsorbed in either the proximal or distal tubule
What triggers the release of renin from granular cells in juxtaglomerular apparatus
Decrease in blood pressure
Decrease in NaCl in blood
Decrease in blood volume
Sympathetic nervous system due to decrease in BP
Which cells sense the amount of NaCl in distal tubule hence triggers renin release
Macula dena cells
ANP is produced by ___ and stored in ____
Produced by the heart
Stored in atrial muscle cells
Trigger of release of ANP
When atrial cells are stretched due to an increase in plasma volume
Effect of ANP
Decrease reabsorption of Na+ -> increase in H2O excretion in urine -> lower BP
Afferent arteriolar vasodilation -> increase in GFR so more Na+ and H2O filtered out
Reduce cardiac output -> lower BP
Reduce vascular resistance -> lower BP
Micturition is controlled by
Micturation reflex
Voluntary tightening of external sphincter
What is the micturition reflex
Involuntary response initiated by stretch receptors in the bladder wall
Contraction of detrusor muscle and opening of the internal and external urethral sphincters
What is the normal pH of arterial blood
7.45
What is the normal pH of venous blood
7.35
Why is it important to regulate pH
H+ can affect enzyme activity
Changes in H+ influence K+ levels
Changes in CNS and peripheral nervous system
Weak acid dissociates partially / completely in solution
Partially
Strong / weak acid sets up an equilibrium
Weak because it dissociates partially only
Adding H+ to the buffer system will cause the equilibrium to
Shift to the left
= more HA less A-
Adding a base to the buffer system will cause the equilibrium to
Shift to the right; because the base is reacting with H+ so less H+
Less H+ = HA will dissociate more to replenish the lost H+ so pH does not change
So Less HA more A-
What is the most important physiological buffer system and what is its significance
CO2 and HCO3 buffer
To control the acid-base balance in body
H2CO3 in the CO2 HCO3 buffer is formed from
CO2 + H2O by carbonic anhydrase
What controls the concentration of HCO3-
Kidneys
What controls the concentration of CO2
Lungs
How do kidneys maintain the acid base balance
It controls the excretion of H+ and reabsorption of HCO3-
How do kidneys excrete fixed amount of H+ to maintain acid base balance
Excretion of H+ as titratable acid (H2PO4)
Excretion of H+ as ammonia (NH4+)
How does the kidney control the concentration of HCO3-
Reabsorption of filtered HCO3-
Formation of new HCO3- to add to the blood
The mechanisms that control the concentration of HCO3- is dependant on
how much H+ is in the tubule - the excretion of H+ is accompanied by synthesis and reabsorption of HCO3- in order to replenish the HCO3- used for buffering
Are all HCO3- reabsorbed
Yes, mainly in proximal tubule
The reabsorption of HCO3- mainly occurs at
Proximal tubule
Describe the formation of new HCO3-
Occurs when the HCO3- in tubular fluid is low
- Secreted H+ into urine in exchange for HCO3- combines with phosphate to form a titratable acid (H2PO4)
- net gain of HCO3-
What is the titratable acid and what is its use
H2PO4; it is the by product for formation of new HCO3- and it can be measured to use as an indicator for body’s acid-base balance
If 40mmol/day of titratable acid is excreted, what does it imply
40mmol/day new HCO3- is gained by the circulation
If 40mmol/day of NH4- is excreted, what does it imply
40mmol/day new HCO3- is gained by the circulation
Total H+ secreted into the tubule Is 4360 mmol/day but total H+ excreted is 60mmol/day. Why isn’t there acidosis
Because most of the H+ secretion is used for HCO3- (base) reabsorption
What is used to assess glomerular function
GFR
Proteinuria
What is used to assess GFR
Serum creatinine
or serum creatinine / urine creatinine
Why is creatinine used to assess GFR
Because it is filtered by the glomerulus freely at a constant rate
Concerns of using creatinine to assess GFR
It isn’t sensitive to changes in GFR until GFR is quite low
Different factors such as muscle mass and diet can confound the measurement
What is eGFR
estimated glomerular filtration rate that is calculated taking into account a person’s age, sex, race, and serum creatinine level
Limitation of eGFR
still not accurate at high GFR level
How is proteinuria (if any) assessed
24 hour urinary collection
Urine dipstick
Protein creatinine ratio
Albumin creatinine ratio
Proteinuria of what value indicates significant glomerular damage
> 150mg/day
Normal dipstick reading, PC, 24 hour protein, and ACR values
Dipstick - negative
PCR - <15
24 hr protein - <0.150
ACR
- female - <3.5
- Male - <2.5
Microalbuminuria lab results
Dipstick - negative
PCR - <15
24hr Urine - <0.15
ACR
- 2.5-30 in males
- 3.5-30 in females
Microalbuminuria is an early sign of
Diabetic nephropathy
What is used to assess tubular function
Urine osmolarity
If tubules are not functioning, the urine osmolarity will be
Urine osmolarity = serum osmolarity
What are the 2 systems that regulate the physiological pH
HCO3- - regulated by kidneys
CO2 - regulated by the lungs
What happens in respiratory acidosis
There is a retention of CO2 by the body
This drives the equilibrium to the right, increasing H+ and HCO3-
The increase in H+ causes acidosis and the overall change in HCO3- is not enough to correct the acidosis due to small changes in H+ causing large changes in pH
What are the compensations for respiratory acidosis
Blood CO2 stimulates H+ secretion into the filtrate
All filtered HCO3- is reabsorbed
H+ continues to be secreted and generate titratable acid and NH4+
Through these processes, acid is excreted and new HCO3- is added to blood
However, because changes in H+ causes a bigger change in pH, the increase in HCO3- cannot fully compensate
