Renal Physiology Flashcards
Renal functions
- regulate blood volume and pressure **
- maintain acid-base balance
- excretion
- gluconeogenesis
- secrete hormones
__% of body weight is water
60%
__% is intracellular fluid
40%
__% is extracellular fluid
20%
Extracellular fluid is composed of
- interstitial fluid
- plasma
- cerebrospinal fluid
Higher concentration of sodium is found in
extracellular fluid compartment
Higher concentration of potassium is found in
intracellular compartment
Higher concentration of chloride is found in
extracellular fluid compartment
Higher concentration of bicarbonate is found in
extracellular fluid compartment
Higher concentration of phosphate is found in
intracellular compartment
Aquaporins
- specialized water-selective channels
- rapid diffusion of water
Osmole
one mole of solute that is dissolved in water
Osmolarity
number of solutes per volume of solution expressed in moles per liter
The more solute, the ___ osmolarity
more
Diffusion
- both water and solute molecules can diffuse across membrane moving from one compartment to the other
Osmosis
- net diffusion across semi-permeable membrane from high water concentrations to low water concentration
- only water can diffuse across membrane, not solutes
Osmotic pressure
- opposing pressure required to stop osmosis completely
- prevents water from coming into cell
Tonicity
- determined by concentration of non-penetrating solutes in extracellular solution
Isotonic
- inside cell and extracellular environment have same osmolarity
- cell volume does not change
Hypertonic
- extracellular fluid has higher osmolarity than inside
- cell will shrink
Hypotonic
- extracellular fluid has lower osmolarity than inside
- cell will swell
Isomotic, hypermotic, hypomotic
- does not take into consideration if solute is non-penetrating or penetrating
Movement of water and solute from interstitial fluid compartment to plasma
absorption
Movement of water and solutes from plasma to interstitial fluid
filtration
Capillary hydrostatic pressure
pushes fluid out of capillary into interstitial fluid
Interstitial fluid hydrostatic pressure
pushes fluid out of interstitial fluid into capillaries
Contribution of plasma proteins to fluid movement
- large and sometimes charged, cannot move in and out of capillaries easily
Osmotic capillary pressure
- high plasma protein concentration moves water into capillaries
Osmotic interstitial fluid pressure
- plasma that escapes into interstitial space and moves water into interstitial space
Net pressure - starling forces
sum of outgoing forces subtract by sum of ingoing forces
Arterial end of capillary has more ____
filtration, fluid moves out of capillary
Venous end of capillary has more ____
absorption, fluid moves into capillary
Water is gained through
- ingestion
- produced as result of metabolism
Water is lost through
- excretion
- utilized in metabolism
How are kidneys located
retroperitoneal
Hilum
inner concave part of kidney
Ureters
drain the formed urine from the kidneys and empty into the bladder
Bladder
- storage organ or sac for formed urine
- receives innervation from autonomic nervous system (para and symp)
Urethra
bladder empties out of body
2 regions of kidneys
- outer portion: cortex
- inner portion: medulla
2 regions of nephrons
- renal corpuscle
- renal tubule
Nephrons
- 1 million in each kidney
- where urine is made
- urine forms where nephrons fuse together and form collecting duct
Renal corpuscle
- cup-like shaped structure with tuft of capillaries
Glomerulus
capillary tuft/loop
Bowman’s capsule
cup the capillary tuft is sitting in
Renal tubule segments
- proximal convoluted tubule
- loop of Henle (descending and ascending limbs)
- distal convoluted tubule
- collecting ducts
Proximal convoluted tubule
- close to renal corpuscle
- twisted
Loop of Henle
- hairpin that bends
- divided into descending and ascending limb
- ascending part of Loop has thicker segment and thinner segment
Distal convoluted tubule
- far away from renal corpuscle
- drains contents in collecting duct
Collecting duct
- collects all formed processed contents and empties in renal pelvis of kidney
Renal corpuscle main function
- initial blood filtering
- inters through afferent arteriole and goes through twists and turns and leaves through efferent arteriole
Bowman’s space
- filtrate enters this space once blood is filtered
- outer wall is made of flat epithelial cells
- cells closet to capillaries are podocytes - foot like processes
- epithelial cells continues to form tubule
Development of renal corpuscle
- nephron will develop first as blind-ended tube - no opening
- growing tuft of capillaries penetrate the expanded end of tubules and invaginates tube. Epithelial differentiates into parietal (outer) and visceral (inner)
- outer layer does not fuse with inner layer and forms a space
Anatomy of renal corpuscle
- capillaries are fenestrated
- podocytes are arranged around the external surface of capillaries
- podocytes interlock their foot processes making filtration slits
Glomerular capillary 3 layers
- endothelial layer - fenestrated
- basement membrane - gel-like mesh
- podocytes - filtration slits
2 types of nephrons
- cortical 85%
- juxtamedullary 15%
Cortical
- everything located in the cortex
Juxtamedullary
- renal corpuscles sit in cortex but closer to medullary area
- loop of Henle and ascending limb found in renal medulla
3 types of renal processes
- filtration
- reabsorption
- secretion
Juxtamedullary nephrons differ from cortical because
- they regulate the concentration of urine
- create osmotic gradients in interstitial space
Peritubular capillary network
- found around proximal convoluted tubules
Vasa recta capillary network
- found associated with juxtamedullary nephrons in medullary portion of kidneys
Glomerular filtration
- fluid in blood is filtered across the capillaries of glomerulus into Bowman’s space
- everything moves into Bowman’s space except large proteins (albumin), blood cells and large negatively charged ions
Tubular reabsorption
- movement of substance from inside the tubule into blood
- ex. glucose
Tubular secretion
- movement of nonfiltered substances from capillaries into tubular lumen
- waste products that did not undergo filtration can be removed from blood by tubular secretion
Ultrafiltrate
- concentration of substrate filtered through the filtration layers is the same in plasma and in filtrate
- cell-free fluid that comes into Bowman’s space
Proteinuria
- condition where some proteins that are not supposed to pass through filtration barrier shows up in filtrate and ultimately through urine
- doe not occur under normal healthy conditions
Glomerular capillary hydrostatic pressure (PGC)
- hydrostatic pressure of the blood that is found in the glomerular capillaries
- favours filtration
Bowman’s space hydrostatic pressure (PBS)
- fluid pressure in Bowman’s space
- opposes filtration
Osmotic force (piGC)
- due to proteins that are present in the plasma
- opposes filtration
Osmotic force (piBS)
- filtrate in Bowman’s space does not contain proteins so there is no osmotic force
- piBS = 0
Positive pressure of glomerular filtration:
pushes protein-free filtrate from plasma out of the glomerulus into Bowman’s space
What factor would contribute to an increase in glomerular filtration rate?
high blood pressure
What factor would contribute to a decrease in glomerular filtration rate
increase in protein concentration in plasma
What percent of plasma volume is filtered into Bowman’s space
20%
Of that 20%, what percent of fluid is reabsorbed and enters the peritubular capillaries
19%
What is the final percent of fluid that is excreted?
1%
Healthy glomerular filtration rate
125 mL/min or 180L/day
Factors that affect GFR
- net glomerulus filtration pressure
- neural and endocrine control
- permeability of the corpuscular membrane
- surface area available for filtration
GFR remains ____ despite large changes in arterial pressure or renal blood flow
constant between 80-180 mmHg
Autoregulation is regulated by changes in (2)
- myogenic reflex
- tubuloglomerular effect
Constriction of the afferent arteriole is due to
myogenic response
Constrict afferent arteriole
decrease GFR
Constrict efferent arteriole
increase GFR
Dilate efferent arteriole
decrease GFR
Dilate afferent arteriole
increase GFR
Tubular glomerular feedback
- juxtaglomerular apparatus
- depending on volume that is flowing, this apparatus will control the autoregulatory processes and affect glomerular filtration rate
What forms juxtaglomerular apparatus
- distal convoluted tubule and glomerular afferent arteriole
3 cell types that control glomerular filtration rate
- macula densa
- juxtaglomerular cells
- mesangial cells
Macula densa
- cells on wall of distal tubule at junction where ascending limb is beginning to form distal tubule
- senses increased sodium load and increased flow fluid
- secrete vasoactive compounds
- secretes paracrine factor adenosine
- part of JGA
Juxtaglomerular cells
- also called granular cells
- sits on top of afferent arteriole
- innervated by sympathetic nerve fibers which can change resistance
- release renin which controls afferent arteriole resistance
- part of JGA
Mesangial cells
- found in triangular region between afferent and efferent arterioles
- allow podocytes to contract and shrinks surface area of glomerular filtration surface
- not part of JGA
Macula densa feedback loop
increase GFR –> increase in flow to the tubule –> flow past the macula densa increases –> paracrine factors from macula densa are secreted –> paracrine factors act on afferent arteriole –> afferent arteriole constricts –> resistance in afferent arteriole increases –> hydrostatic pressure drops in glomerulus (PGC) –> GFR decreases
Filtered load
amount of substance that is filtered by the kidneys or how much of the load is filtered into Bowman’s space
Filtered load = GFR x concentration of substance in plasma
Substance excreted in urine < filtered load
reabsorption has occured
Substance excreted in urine > filtered load
secretion has occurred
What percent of plasma enters the glomerular capillaries is filtered into Bowman’s space
20%
Inulin
- filtered and no secretion or reabsorption
Creatinine
- filtered and no secretion or reabsorption
Electrolytes
- filtered and partially reabsorbed
Glucose and amino acids
- filtered and completely reabsorbed
Organic acids and bases
- filtered and completely secreted
What percentage of water is filtered and reabsorbed
99%
What percentage of sodium is filtered and reabsorbed
99.5%
What percentage of glucose is filtered and reabsorbed
100%
What percentage of urea is filtered and reabsorbed
44%
2 pathways of reabsorption
- paracellular transport - diffusion occurs mostly through tight junctions
- transepithelial transport - mediated transport involving transporters
Pathway of transepithelial transport
- substance moves from the apical membrane and across the basolateral membrane in reabsorption
Reabsorption of sodium
- passively moves across luminal surface down concentration gradient
- actively transported across basolateral membrane via Na+/K+ pump with ATP (3 Na+ out, 2 K+ in)
- bulk flow from interstitial fluid into peritubular capillaries
Reabsorption of glucose
- clearance of glucose is zero
- active transport across luminal side by SGLT protein (sodium dependent)
- facilitated diffusion across basolateral side using carrier protein GLUT
- Na+/K+ pump establishes gradients
Glucosuria
- above renal threshold glucose appears in the urine
Reabsorption of glucose is linear up to
300 mg/ 100 mL plasma
- after the graph reaches a plateau
Transport maximum (Tm)
- no more reabsorption after this point
- all SGLT proteins are saturated and binding sites are occupied
- glucose will show up in urine
Diabetes mellitus
- capacity to reabsorb glucose is normal (SGLT work normal)
- filtered load is greatly increased and beyond threshold level
- patient has too much glucose in their blood due to insulin not working correctly
Renal glucosuria
- Benign glucosuria or familial renal glucosuria
- genetic mutation of SGLT transporter leading to inability to transport glucose from luminal side
- filtered load may be small or normal
- glucose shows up in urine
Reabsorption of urea
- freely filtered at the glomerulus
- sodium and anions move out of lumen extracellularly
- water flows out of lumen by osmosis following reabsorption of sodium
- urea will diffuse down concentration gradient
- urea reabsorption is dependent on water reabsorption
Tubular secretion
- mostly H+ and K+
- penicillin, choline, creatinine
- creatinine undergoes secretion where inulin does not
- couples to reabsorb Na+
What is renal clearance
- way of measuring how well the kidneys remove substances
- looks at excretory products
- measures the volume of plasma from which a substance is completely removed from the kidney per unit of time
Clearance formula
Clearance of “S” = (Us x V) / Ps
- Us = concentration of substance S in the urine
- V = volume of urine passed, mL/min
- Ps = concentration of substance in plasma
Clearance of glucose
- should always equal O
Clearance of inulin
- polysaccharide not found in the body: intravenously or from plant foods
- 180 L/day or 125 mL/min
- equals to glomerular filtration rate
- measuring the clearance of inulin will provide a measure for GFR
Clearance of creatinine
- product of muscle metabolism
- clearance of creatinine slightly overestimates GFR
- used to clinically estimate GFR
Is clearance of substance X is greater that GFR
substance X is being secreted
Is clearance of substance X is less than GFR
substance X is being reabsorbed
Role of proximal convoluted tubule
- reabsorbs majority of water and non-waste plasma solutes
- major site of solute secretion except potassium
- 80% reabsorption
Role of loop of Henle
- creates an osmotic gradient in interstitial space
- little reabsorption
Role of distal convoluted tubule
- site of major physiological control for water reabsorption
- major homeostatic mechanisms of fine control of water and solute to produce urine
- 12-15% reabsorption
Sources of water gain
- ingested liquid
- water from oxidation of food
Avenues of water loss
- skin, respiratory airways
- sweat
- GI tract, urinary tract, menstrual flow
Water reabsorption in proximal tubules
- 67%
- aquaporins always stay open (AQP-1)
- passive mechanism
Water reabsorption in Loop of Henle
- 15%
- passive mechanism
- mainly descending limb
- aquaporin (AQP-1)
- ascending limb is impermeable to water
Water reabsorption in distal tubule
- no reabsorption as no aquaporins
Water reabsorption in collecting duct
- 8-17%
= depends on body’s state of hydration - different types of aquaporins
- vasopressin and ADH control aquaporins
Highest osmolarity is found at the ____ of the Loop of Henle
bottom
The interstitial fluid is ____ compared to the Loop of Henle
hyperosmolar
Net result of water and salt absorption in the Loop of Henle
- gradient difference between interstitial space and ascending limb of 200 mOsm
- water moves out of descending limb
- solute/NaCl out of ascending limb
Multiplication in the Loop of Henle
- as fluid moves down the loop, the gradient is multiplied and at the bottom is very hyperosmolar
- 300 mOsm –> 1400 mOsm
- created concentrated urine
When fluid reached the top of ascending limb it is
- hypoosmotic
- 80 mOsm
What happens to water in cortical collecting duct
- water moves out by vasopressin (ADH)
- filtrate becomes hyperosmolar again (300 mOsm)
Different species with different length loops
short loops - does not need to conserve water
long loops - needs to conserve more water, hyperosmolar gradient is greater to conserve more water
Vasa recta
- blood vessels that run parallel to loop of Henle
- counter current blood flow
- loop-like circuits at each gradient level to maintain salt gradient
- permeable to both solutes and water
Descending limb of vasa recta
- salt enters, water exits
How much urea is excreted of the original amount
15%
- minimal uptake of urea by vasa recta and recycling urea in interstitial space helps maintain high osmolarity
Why is there a need for concentrated urin
- kidneys save water by producing hyperosmotic urine
Mechanisms used to maintain hyperosmotic environment of the medulla
- counter-current anatomy and opposing fluid flow through Loop of Henle of juxtamedullary nephrons
- reabsorption of NaCl in ascending limb
- impermeability of ascending limb to water
- trapping of urea in medulla
- hairpin loops of vasa recta maintains hyperosmotic
Diuresis
- void
- produce a large amount of urine
Anidiuresis
- reduction of the excretion of large volume of urine
ADH/vasopressin
- peptide hormone
- hypothalamus in supraoptic nucleus (SON)
- cells sense a reduction in plasma volume
- site of action: collecting duct
AQP2
- insertion on luminal side and is regulated by ADH
AQP3 and AQP4
- basolateral membrane and not regulated by ADH
ADH mechanism
- ADH binds to receptor on cell
- activates adenylyl cyclase, ATP converted to cAMP
- activates protein kinase A, phosphorylates proteins
- transcription factors activates
- AQP2 are inserted into luminal membrane
- water diffuses into the cell then out of cell into interstitial fluid via AQP3/4
if levels of ADH are very low, AQP2 channels are
- recycled or taken back by endocytosis
- diuresis
Diabetes insipidus
- large quantities of urine
Central diabetes inspidius
- failure to release ADH from posterior pituitary
Nephrogenic diabetes insipidus
- ADH is secreted normally but hormone does not function normally
- problem with receptor or intracellular signaling pathway
- problem within cells of nephron
When ADH is increased, AQP2 levels _____, water is _____, pee _____
- increase
- reabsorbed
- less
Mechanisms when there is water deprivation
- osmolarity of plasma increases
- osmoreceptors in hypothalamus are stimulated
- increased release of ADH
- retention of water
- thirst centers in hypothalamus stimulated to increase water intake
- STEEP GRADIENT
Mechanisms when there is water intake
- lower osmolarity of plasma
- osmoreceptors in hypothalamus sense block
- ADH is blocked
- large volume of fluid is excreted
- NO STEEP GRADIENT
Water diuresis
only water is excreted without excess solute in urine
Osmotic diuresis
excess solute in urine associated with high levels of water excretion
- uncontrolled diabetes mellitus
Regulation of Na+ levels
- sodium is never secreted, it is excreted
- total body sodium stays within small range
- regulated by changing the volume of urine excreted
Sodium excreted equation
sodium excreted = sodium filtered - sodium reabsorbed
Short term regulation for low sodium plasma
- Baroreceptors - sensitive to stretch
- found in carotid tinus, aortic arch, veins, intrarenal
- JG cells of JGA
- blood pressure –> stretch –> nerve impulse frequency
- processed in medulla oblongata
- activation of ANS
Long term regulation for low sodium plasma
- Aldosterone via renin/angiotensin II system
Long term regulation for low sodium plasma - Aldosterone
- steroid hormone
- secreted from adrenal cortex
- triggered by low plasma volume
- regulates Na+ reabsorption - induces the synthesis of sodium transport proteins
- site of action: distal tubule and cortical collecting ducts
Long term regulation for low sodium plasma - Renin
- enzyme
- sensor for low sodium chloride concentration in blood
- converts angiotensinogen to angiotensin I
Long term regulation for low sodium plasma - Angiotensin converting enzyme (ACE)
- converts angiotensin I to angiotensin II
- angiotensin II acts on adrenal cortex to release aldosterone
ACE inhibitor
- drug to manage high blood pressure by blocking the ACE enzyme
- with no aldosterone stimulating sodium reabsorption, sodium will not be reabsorbed and lost in urine, lowering blood pressure
3 triggers for aldosterone release in renin-angiotensin mechanism
- sympathetic stimulation of renal nerves
- decrease in filtrate osmolarity
- decrease blood pressure
Long term regulation for low sodium plasma - Juxtaglomerular cells
- walls of afferent arteriole
- mechanoreceptors
- sense circulating plasma volume
- secretes renin
JG cells receive 3 inputs
- sympathetic input from extrarenal baroreceptors
- intrarenal baroreceptors
- signals from macular densa
Long term regulation for low sodium plasma - Macula densa
- wall of distal convoluted tubule
- chemoreceptors
- sense NaCl load of filtrate
Regulation for high sodium plasma
- Atrial natriuretic peptide
- synthesized and secreted by cardiac atria
- site of action: inhibits aldosterone, inhibits Na+ reabsorption, increases GFR and Na+ excretion
- stimulated by: increased Na+ concentration, increased blood volume, atrial distention (TRUE SENSOR)
K+ excretion equation
K+ excreted = K+ filtered - K+ reabsorbed + K+ secreted
Hyperkalemia
- excess K+ in the blood
Regulation of potassium
- K+ levels are regulated by aldosterone by acting on cortical collecting duct to increase K+ secretion in urine in response to high extracellular K+ concentration
How can changed in pH modify activty of proteins?
- changes nature and shape of proteins that alter activity
- changes in neuronal activity
- hydrogen ion concentrations associated with K+ imbalances
- irregular cardiac beats
Volatile acid
CO2
Nonvolatile acids
- phosphoric acid
- sulfuric acid
What amino acids produce sulfuric acid?
Cysteine and methionine
What amino acids product hydrochloric acid?
Lysine, arginine, histidine
4 ways to gain hydrogen ions
- generation of H+ from CO2
- non-volatile acids generated from protein metabolism
- loss of bicarbonate in diarrhea
- loss of bicarbonate in the urine
3 ways to lose hydrogen ions
- vomiting
- urine
- hyperventilation
Extracellular buffer system
bicarbonate (CO2/HCO3-)
Intracellular buffer systems
- phosphate ions and associated proteins
- hemoglobin
Carbonic acid formular
CO2 + H2O <-carbonic anhydrase-> H2CO3 <–> H+ + HCO3-
Short term balance of H+
lungs
- increase H+ - stimulated ventilation
- decrease H+ - inhibits ventilation
Long term balance of H+
kidneys
- excretion or reabsorption in urine
Key concept of kidney regulation of H+
when 1 H+ ion is lose from the body, 1 HCO3- is gained by the body
Alkalosis
- kidneys excrete more bicarbonate into urine
Acidosis
- kidney cells synthesize new bicarbonate and send it t blood
Reabsorption of HCO3-
- acidosis - H+ increased
- bicarbonate is added to blood
- active process
- proximal tubule, ascending loop of Henle, cortical collecting duct
Mechanism 1 - addition of HCO3- to plasma
- when more H+ is secreted than there is HCO3-
- extra H+ binds to HPO42-
- HCO3- is generated by tubular cells and diffuses into plasma
- net gain of HCO3- in plasma
Mechanism 2 - addition of HCO3- to plasma
- only in proximal tubule
- uptake of glutamine from glomerular filtrate
- NH4+ and HCO3- formed inside cells
- NH4+ is actively secreted via Na+/NH4+ counter transport into lumen
- HCO3- added to plasma
Respiratory acidosis
- decreased ventilation
- increased blood PCO2
- occurs in emphysema
- kidneys compensates by secreting H+ and lowers plasma H+
Respiratory alkalosis
- increased ventilation
- decreased blood PCO2
- happens in high altitude
- kidney compensates by excreting HCO3-
Metabolic acidosis
- occurs in diarrhea
- severe mellitus
- results in increased ventilation
- results in increased H+ secretion
Metabolic alkalosis
- prolonged vomiting
- results in decreased ventilation
- results in increased HCO3- excretion
