UR Learning Objectives Flashcards
4 basic processes – filtration, reabsorption, secretion, excretion.
- Glomerular filtration: glomerulus (blood) to capsular space (filtrate)
- Tubular reabsorption: renal tubule (fltrate) to peritubular capillaries (blood)
- Tubular secretion: peritubular capillaries (blood) to renal tubule (filtrate)
- Urinary excretion: elimination from body by combining 3 processes
- excreted = filtered + secreted - reabsorbed
Principle of filtration and what makes the glomerulus such a good filter.
Principle of filtration: use pressure to move fluids/solutes through a membrane
What makes glomerulus such a good filter?
- volume per unit time (150-180 L/day) is more efficient than other capillary beds (4 L/day for systemic capillaries) with these factors…
- larger surface area
- greater permeability (vessel walls have pores that are 45x leakier than typical systemic capillaries to allow more fluid to go through)
- higher blood pressure (around 60 mmHg) than typical systemic capillaries (15-35mmHg)
Starling Forces and how combine to produce glomerular filtration.
4 starling forces
- blood hydrostatic pressure (PGC): around 60 mmHg
- filtrate osmotic pressure (piCS): around 0 mmHg*these two favour filtration: glomerulus to capsular space
- filtrate hydrostatic pressure (PCS): around 15 mmHg
- blood osmotic pressure (piGC): around 29 mmHg*these two oppose filtration: capsular space to glomerulus
- combine for net filtration pressure (NFP)
- NFP = (PGC + piCS) - (PCS + piGC)
- this is basically favour filtration - oppose filtration
- healthy: favour filtration over entire glomerular capillary surface area (NFP always positive)
- in systemic capillaries, filtration favoured at start and opposed at end of capillary bed
Renal autoregulation – myogenic mechanism and tubuloglomerular feedback – for glomerular filtration rate homeostasis.
Renal autoregulation
- intrinsic mechanisms in kidney to keep GFR within certain tolerance despite blood pressure (homeostasis)
- used to separate blood pressure changes from GFR changes
- process: change blood pressure - change PGC - change NFP - change GFR
- there are 2 renal autoregulation processes
- myogenic mechanism
- altering contraction of smooth muscle around arteriole by altering radius - alter PGC - alter NFP - alter GFR
- either vasoconstrict to decrease or vasodilate to increase
- responds in seconds
- stimulus is blood pressure change affecting PGC and stretch of arteriole
- this means stimulus and response is change in diameter?
- tubuloglomerular feedback
- JGA alter release of nitric oxide - alter afferent arteriole radius (more or less vasodilation) - alter PGC - alter NFP - alter GFR
- stimulus is blood pressure change affecting PGC and salt concentration delivery at macula densa cells of juxtaglomerular apparatus (JGA)
- slower to respond as there are more steps
- basically, salt changes are detected in area and nitric oxide release by JGA in response
Neural factors to alter glomerular filtration rate.
- extrinsic mechanisms outside kidneys to alter GFR under some circumstances
- involve neural and/or hormonal changes
- changes must be stronger than renal autoregulation correcting (changes low enough, renal autoregulation can handle itself)
Summary of flow chart example (vice verse likely true)
- CV stuff like plasma volume or atrial pressure or SV decrease
- baroceptors in relevant location detect
- vasomotor centre
- increased sympathetic firing to kidney to release epinephrine or norepinephrine
- kidney: greater binding of alpha receptor on afferent arteriole to increase vasoconstriction
- decrease PGC - decrease NFP - decrease GFR
*arterial pressure decrease has additional response to directly change PGC
- arterial pressure altered
- change GFR (by changing PGC directly)
- does this change without altering renal sympathetic firing
Hormonal factors to alter glomerular filtration rate.
RAAS: renin, angiotensin, aldosterone system
Part 1: formation of angiotensin ll
- plasma volume altered
- alteration of salt concentration delivery detected by macula densa
- alteration of arterial blood pressure changes renal sympathetic firing
- juxtaglomerular cells triggered and secrete and release renin into blood
What happens in blood
- angiotensinogen (inactive) released from liver continuously into blood
- angiotensinogen → active angiotensin l by renin that is now circulating
- angiotensin l → angiotensin ll by angiotensin converting enzyme (ACE released mainly by lung and kidney endothelial cells)
- angiotensin ll decreases GFR by…
- binding to alpha receptor to vasoconstrict afferent arterioles
- contracting mesangial cells to decrease glomerular capillary surface area
*refer to flow chart example
ANP: atrial natriuretic peptide
- altered plasma volume → alter distention (stretch) of atria
- distention controls release of ANP secretion and release into blood
- ANP increases GFR by
- binding to beta 2 receptors to vasodilate afferent arterioles
- relaxes mesangial cells to increase glomerular capillary surface area
*refer to flow chart example
Structures of renal tubule for reabsorption and secretion.
Secretion: peritubular capillaries → renal tubule
Reabsorption: renal tubule → peritubular capillaries
Areas
- tubular lumen: inner cavity of renal tubule
- tubular epithelial cell: cells that make up inner wall of renal tubule
- interstitial fluid: ECF surrounding renal tubule
- blood vessel: peritubular capillaries
- tight junction: connecting point between adjacent tubular epithelial cells
Between lumen and peritubular capillaries
- paracellular: between epithelial cells
- transcellular: through epithelial cells
Going transcellular
- apical: between tubule lumen and inside tubular epithelial cell
- basolateral: between inside tubular epithelial cell and IF
Active and passive movements in renal tubule.
Active (refer to diagram)
- at least 1 ion moving low to high concentration (moving up gradient)
- at least 2 ions move together (same direction is co transport, opposite direction is counter transport)
- primary: ATP breakdown to ADP and Pi to energize pumping of ions across membrane, both ions moving up gradient
- secondary: movement responding to changes produced by primary, one ion moves down gradient while one moves up (or more than 2 ions involved)
Passive
- high to low concentration (moving down gradient)
- Chemical
- simple diffusion: ion moves straight through membrane
- facilitated diffusion: membrane protein needed to provide passage
- osmosis: for water, aquaporin involved often (water membrane protein)
- Electro
- separation of electrical charge (charge imbalance)
- positve charge → negative charge and vice versa
- electrochemical is combination of all these things above
- semipermeable means only some things go through
Specific movement paths for solutes in renal tubule.
- proximal tubule → loop of Henle → distal tubule and collecting duct
- proximal tubule
- reabsorption
- sodium: 65%
- glucose and amino acids: 100%
- secretion
- hydrogen: variable amount dependent on blood levels
- obligatory water reabsorption: water that moves during following of solutes
- 65% water reabsorbed in proximal tubule because lots of aquaporins make movement easy
- two processes
- initial process (sodium, glucose, amino acids)
- solute movement alter osmotic pressure
- water follows to correct OP gradient
- secondary process (simple diffusion ions)
- initial water movement creates concentration gradients for other ions (Ca, Cl, K, Mg) that can move with simple diffusion
- simple diffusion ions move and lower OP where left and high OP where moved
- water again responds to correct OP gradient
- initial process (sodium, glucose, amino acids)
- loop of Henle: water movement only in descending loop of Henle because no aquaporins in ascending loop of henle
- reabsorption
- water: 15% (from following OP gradients in proximal tubule)
- primary and secondary transport move
- sodium: 25%
- chloride: 35%
- potassium: 25%
- reabsorption
- distal tubule and collecting duct
- reabsorption
- sodium 6-9%
- water: depends on hormonal regulation, NOT OBLIGATORY ANYMORE
- secretion
- potassium: dependent on hormonal regulation and dietary intake
*note that sodium being reabsorbed and potassium being secreted, remind you of anything?
- potassium: dependent on hormonal regulation and dietary intake
- reabsorption
- reabsorption
Obligatory water movement process.
Obligatory water reabsorption: water that moves following solutes
- 65% of water is reabsorbed in the proximal tubule because of amount of aquaporins
two processes
- initial process (sodium, glucose, amino acids)
- solute movement alter osmotic pressure
- water follows to correct OP gradient
- secondary process (simple diffusion ions)
- initial water movement creates concentration gradients for other ions (Ca, Cl, K, Mg) that can move with simple diffusion
- simple diffusion ions move and lower OP where left and high OP where moved
- water again responds to correct OP gradient
Descending loop of Henle
- 15% because still following OP gradients created in proximal tubule
*obligatory water reabsorption ends once we reach distal tubule and collecting duct
Contributions of hormones to ion and facultative water movement – continued.
ANP, remember it’s based off distention
- plasma volume increases
- atrial muscle stretch increases
- atria: increased secretion and release of ANP into the blood
- collecting duct: decrease sodium and water reabsorption by inhibiting apical and basolateral pathways (makes sense because increase plasma volume = over-hydration
- obviously, sodium and water excretion will increase (sodium will leave and water will follow)
- think of this like sweat and hydration, if hydration is good (plasma volume increases) then sweat will decrease (salt)
Contributions of hormones to ion and facultative water movement.
Contributions of hormones to ions
- aldosterone
- angiotensin ll → adrenal gland to secrete and release aldosterone into bloodstream → collecting duct to increase sodium and water reabsorption and increase potassium secretion → decrease sodium and water excretion and increase potassium excretion
- aldosterone binds to apical membrane channels and basolateral primary pumps
- facultative water reabsorption: 0-19.8%, dependent on need
- ADH (anti-diuretic hormone)
- makes up for lack of aquaporins in collecting duct by causing insertions of aquaporins on apical membrane
- facultative water reabsorption
- normal hydration: 19% reabsorbed, 1% excreted, 1-2L/day urinary excretion
- dehydration: 19.8% water reabsorbed, 0.2% excreted, because of large ADH increasing aquaporins
- overhydration: as low as 0% reabsorbed, 20% excreted, due to ADH absence decreasing aquaporins
- example
- plasma volume → venous, atrial, arterial pressures, OP → hypothalamus for osmoreceptor firing
- posterior pituitary: ADH secretion and release into blood
- collecting ducts: number of aquaporins and water reabsorption
- water excretion
Immersion diuresis.
When body is immersed into water, the pressure causes a fluid compartment shift from IF to plasma. The increased plasma volume → increased ANP (distention controlled), decreased ADH
Urinary flow.
When urine leaves kidneys and flows into ureters that lead to bladder. Contractions of ureter wall smooth muscle do this along with gravity. Urine is then stored in bladder and voided during excretion. 3 neural pathways.
- parasympathetic
- sympathetic
- somatic motor
Bladder filling, micturition reflex, and voluntary control.
Filling: bladder distends during filling up to 800-1000mL, at around 200-400mL, mechanoreceptors send sensation of fullness afferent signal to brain and that gives brain conscious awareness of desire to urinate
- detrusor (smooth muscle): parasympathetic inhibited (relax)
- internal urethral sphincter (smooth muscle): sympathetic stimulated (contract)
- external urethral sphincter (skeletal muscle): somatic motor stimulated (contract)
Micturition (voiding) reflex: spinal reflex, first part is mechanoreceptors sending afferent to spinal cord, second part is efferent signal returns from spinal cord and causes detrusor to contract and sphincters to relax, leads to urinary excretion
- detrusor (smooth muscle): parasympathetic stimulated (contract)
- internal urethral sphincter (smooth muscle): sympathetic inhibited (relax)
- external urethral sphincter (skeletal muscle): somatic motor inhibited(relax)
Voluntary control: ability to stop micturition reflex, afferent signal to spinal cord also to pons and higher brain centres. This is where we decide to send efferent signal from pons/higher brain centres to maintain somatic motor stimulation and contract external urethral sphincter, allows override but for limited time
- detrusor (smooth muscle): parasympathetic stimulated (contract)
- internal urethral sphincter (smooth muscle): sympathetic inhibited (relax)
- external urethral sphincter (skeletal muscle): somatic motor stimulated (contract)
Difference between diuresis and natriuresis.
Diuresis: elevated urine flow rate
- diuretic: substance to cause diuresis
- excrete high volume of diluted (water-based) urine
Natriuresis: elevated urine flow rate AND elevated sodium content
- natriuretic: substance to cause natriuresis
- excrete high volume of salty urine
Both used to treat hypertension by decreasing blood volume
Hyponatremia.
Seen in endurance sports with high losses of electrolytes (sodium, potassium, etc) and water
Becomes an issue if:
1. consuming large amounts of water to replace losses but not replacing solutes as well
2. alters osmotic pressure (remember equation)
3. fluid compartment shifts leading to cells swelling
4. enough water movement into cells causing water intoxication
*can also see hyponatremia with excessive blood loss, vomiting, or diarrhea with large amounts of just water replacement
Balance (gain and loss) and intake factors for water.
Intake (gain)
- liquid
- food
- metabolic (body chemcial reactions ex. H+ +HCO3- -> H2CO3 -> H2O + CO2 to produce water)
Output (loss)
- sweat
- feces
- urine
- insensible (from skin epithelial cells and breathing, we are not aware of this type of loss because it’s so hard to detect)
- however, doesn’t mean that sweat is insensible! sweat comes from sweat glands, water loss comes from epithelial cells
Water intake (thirst): kidneys can only maximize reabsorption and minimize excretion so much, we still need intake to replace the significant water output, especially after exercise
Stimulating thirst centre in hypothalamus
- mechanoreceptors (stretch): detect blood volume changes
- baroreceptors: detect blood pressure changes
- osmoreceptors: detect blood osmotic pressure changes (most senstive and important)
- dry mouth
- also psycholoigcal and conditioned responses for thirst like learning drinking cycldes for marathon
Acid-alkaline balance and how it is achieved by chemical buffering, respiratory, and renal processes.
Acid-alkaline balance
- alkalosis > 7.4
- decreasing acidity, increase alkalinity, higher pH, lower H+
- acidosis < 7.35
- increasing acidity, decreasing alkalinity, lower pH, higher H+
- many metabolic processes rely on this balance for optimal functioning
- strong regulatory hydrogen balance
- Chemical buffering (immediate response)
- in response to alkalosis: H-buffer releases hydrogen and buffer (buffer + H+)
- in response to acidosis: hydrogen binds buffer to from Hxbuffer (having hydrogen bind mitigates hydrogen ions)
- temporarily ALTERS hydrogen levels, doesn’t eliminate hydrogen from body or add it to body permanently
- basically, high acidity = hydrogen binds to buffer to “not count”, high alkalosis = hydrogen floats freely to create acidity
- best 3 chemical buffers- bicarbonate buffer (H2CO3 = H+ + HCO3-)
- major extracellular buffer
- in response to alkalosis: carbonic acid releases hydrogen and bicarbonate
- in response to acidosis: hydrogen binds bicarbonate to form carbonic acid
- phosphate buffer (H2PO-4 = H+ + HPO2-4)
- major intracellular buffers
- in response to alkalosis: dihydrogen phosphate release hydrogen and monohydrogen phosphate
- in response to acidosis: monohydrogen phosphate binds hydrogen to form dihydrogen phosphate
- protein buffer (hemoglobin: Hb-H = H+ + Hb)
- major intracellular buffer
- in response to alkalosis: protein releases hydrogen
- in response to acidosis: protein binds hydrogen
- bicarbonate buffer (H2CO3 = H+ + HCO3-)
- respiratory (minutes to respond)
- breathing buffer
- alter ventilation → alter CO2 → alter hydrogen
- in response to alkalosis: reduce ventilation to increase CO2 and increase hydrogen
- in response to acidosis: increase ventilation to decrease CO2 and decrease hydrogen - Renal (hours or days to respond)
- urinary buffer: kidneys alter either hydrogen and/or bicarbonate
- Renal mechanism 1- equation H2O + CO2 = H2CO3 = H+ + HCO3-
- cell uses water and carbon dioxide to form H+ and HCO3- (right side of equation)
- H+ is secreted and binds to filtered HCO3- to form water and CO2 in tubule lumen (this will most likely be reabsorbed later unless there is an excess
- HCO3- reabsorbed into peritubular capillaries
- for every one HCO3- filtered, there is one reabsorbed
- Renal mechanism 2 - basically same as renal mechanism except…
- H+ secreted and binds to filtered HPO4^2- to form H2PO4^-
- for every one filtered HPO4^-, there is one reabsorbed HCO3-
- Renal mechanism 3 - glutamine (amino acid) from 3 possible sources: filtered, peritubular capillaries, and epithelial cell
- cell produces ammonium NH4+ and HCO3- from glutamine
- NH4+ secreted into tubule lumen (will be excreted)
- HCO3- reabsorbed into peritubular capillaries
- for every one glutamine, there is one reabsorbed HCO3-
Summary of renal
- in response to acidosis, we try to maximize
- renal mechanisms 1 and 2 secrete hydrogen and reabsorb bicarbonate
- renal mechanism 3 secretes ammonium and reabsorbs bicarbonate
- secreted hydrogen combines with bicarbonate or monohydrogen phosphate to form water and CO2 → likely reabsorbed or excreted in urine
- formed dihydrogen phosphate and secreted ammonium excreted in urine for excretion of acidic urine
- in response to alkalosis, we try to minimize
- water and CO2 breakdown inside cell
- glutamine movement into cell
- hydrogen and ammonium secretion so little bicarbonate reabsorption
- significant amounts of filtered bicarbonate and filtered monohydrogen phosphate excreted in urine for excretion of alkaline urine
Metabolic and respiratory imbalances in response to acidosis and alkalosis.
- metabolic acidosis: high H+ from non-CO2 path
- detected as low blood bicarbonate
- common source is intense exercise → lactate production
- metabolic alkalosis: low H+ from non-CO2 path
- detected as high blood bicarbonate
- common sources: vomiting/diarrhea or alkaline ingestion which is a type of blood doping
- respiratory acidosis: high H+ from CO2 changes
- detected as high blood carbon dioxide
- common source is hypo/reduced ventilation
- respiratory alkalosis: low H+ from CO2 changes
- detected as low blood carbon dioxide
- common source is hyperventilation
