Renal Physiology 3 Flashcards
what is the basic unit of the kidney and what is its function
Nephron is the basic unit of the kidney and its function is to separate water ions and small molecules from the blood, filter out wastes and toxins and facilitates the concentration of urine
what is the Glomerulus and the Bowmans capsule
Glomerulus is a tuft of glomerular capillaries which are covered by epithelial cells and are encased in bowmans capsule
large amounts of fluid are filtered from the blood
fluid filtered from the glomerular capillaries flows into bowmans capsule and then into the proximal tubule
Actively reabsorbed and passively reabsorbed contents of the Proximal tubule as well as some of the enzymes found here
Actively rebsorbed: -85% sodium bicarbonage -65% sodium chloride 65% potassium 100% glucose and amino acids
Passively reabsorbed:
-water
Na/K ATPase maintains low intracellar Na concentrations sending out into the blood
Carbonic anhydrase will catalyze the formation of carbonic acid from CO2 and H20
Acid and base secretory systems secrete drugs into the lumen from the blood
Na/H (NHE3)
-Na in cell and H+ out into lumen
Parts of the Loop of henle and what they reabsorb and their corresponding transporters
THin descending loop: water reabsorption
Thin ascending loop: relatively impermeable to water and other ions/solutes
THick ascending limb:
- impermeable to water
- 25% sodium reabsorption
- Na/K/2Cl cotransporter (NKCC2) establishes the ion concentration gradient in the interstitum
- increase in K+ concentration in the cells causes back diffusion of K+ into the tubular lumen, allowing a lumen positive electrical potential to drive reabsorption of cations (Mg, Ca) via the paracellular pathway
result is the tubular fluid is concentrated in the descending limb and diluted in the ascending limb
Distal convoluted tubule, what it reabsorbs and its corresponding transporters
- 10% NaCl reabsorbed
- relatively impermeable to water
- Na/Cl cotransporter (NCC) actively transports NaCl out of lumen
- Ca is passively reabsorbed by calcium channels (regulated by PTH)
Result: tubular field is diluted
Collecting tube: Epithelial sodium channel
ENaC:
- responsible for 2-5% of Na reabsorption
- creates electrical gradient that facilitates K secretion down the concentration gradient
- The most important site of K secretion by the kidney
- site at which all dirutetic induced changes in K+ balance occur = more Na delivered to collecting tubule the more K secretion
- Proton pumps increase urine acidity
Collecting tubule: Aldosterone effect
Increases the expression of ENaC and basolateral Na/K ATPase which increases Na reabsorption and K secretion leading to water retention and increase in blood volume and BP
Collecting ductL ANtidiuretic hormone (vasopressin) effect
- Controls permeability of the collecting tubule to water by regulating the expression levels of aquaporin-2 (AQP2) water channels
- No ADH means the collecting duct is impermeable to water
- ADH levels are controlled by serum osmolality and volume status
- Alcohol decreases ADH release and increases urine production
REsult: tubular fluid is concentrated
what location is the urine the most dilute, medium, and least
In the Cortex: 300
-most dilute
In the Outer medulla: 400-600
-medium
Inner medulla: 900-1200
-most concentrated
Function, Water permeability and Primary transporter in apical membrane and Diuretic: Proximal convoluted tubule
Function: REabsorption of 65% of filtered Na/K/Ca/Mg, 85% of bicarbonate and nearly 100% of glucose and amino acids
Isoomotic for water
Water permeabillity: Very high
Apical transporter: Na/H (NHE3) carbonic anhydrase
Diuretic: Carbonic anyhydrase inhibitor
Function, Water permeability and Primary transporter in apical membrane and Diuretic Proximal tubule straight segments
Function: Secretion and reabsorption of organic acids and bases, including uric acid and most diuretics
Water permeabillity: Very high
Apical transporter: acid, uric acid and base transporters
Diuretic: None
Function, Water permeability and Primary transporter in apical membrane and Diuretic Thin descending limb of loop of henle
Function: Passive reabsorption of water
Water permeabillity: high
Apical transporter: Aquaporins
Diuretic: None
Function, Water permeability and Primary transporter in apical membrane and Diuretic Thick ascending limb of loop of henle
Function: active reabsorption of 15-25% of filtered Na/K/Cl and secondary reabsorption of Ca and Mg
Water permeabillity: Very low
Apical transporter: Na/K/2Cl (NKCC2)
Diuretic: Loop diuretics
Function, Water permeability and Primary transporter in apical membrane and Diuretic Distal convoluted tubule
Function: Active reabsorption of 4-8% of filtered Na and Cl and Ca reabsorption under the parathyroid hormone control
Water permeabillity: Very low
Apical transporter: Na/Cl (NCC)
Diuretic: THiazides
Function, Water permeability and Primary transporter in apical membrane and Diuretic Cortical collecting tubule
Function: Na reabsorption (2-5%) coupled to K and H secretion
Water permeabillity: Variable, controlled by vasopressin
Apical transporter: Na channels (ENaC), K channels, H transporter, aquaporins
Diuretic: K+ sparring diuretic
Function, Water permeability and Primary transporter in apical membrane and Diuretic Medullary collecting duct
Function: Water reabsorption under vasopressin control
Water permeabillity: Variable, controlled by vasopressin
Apical transporter: Aquaporins
Diuretic: Vasopressin antagonist
Diuretics and their functions
A diuretic is an agent that increases urine volume, while a natriuretic causes an increase in renal sodium excretion
Diuretics increase the rate of urine flow and sodium excretion
Used to adjust the volume and or composition of body fluids in a variety of clinical situations including
-Edematous state: heart failure, kidney disease and renal failure, liver disease (cirrhosis)
-Nonedematous states: Hypertension, nephrolithiasis (kidney stones), hypercalcemia, and diabetes insipidus
What are some diuretic targets
Specific membrane transport protiens
- Sodium/potassium/chloride cotransporter (loop diuretics)
- Sodium/chloride cotransporter (thiazide diuretics)
- Sodium channels (potassium-sparring diuretics)
Enzymes
-Carbonic anhdrase (carbonic anhydrase inhibitors)
Hormone receptors
-mineralocorticoid receptor (potassium-sparing diuretics)
Carbonic Anhydrase Inhibitors
MOA: inhibits the membbrane bound and cytoplasmic forms of carbonic anhydrase
Results:
- decrease H+ formation inside the PCT
- decrease in Na+/H+ antiport (NHE3)
- Increase Na and HCO3- in lumen
- Increase in Diuresis
Urine pH is increased and pH is decreased
Loop Diuretics
MOA: Inhibit the luminal Na/K/2Cl cotransporter (NKCC2) in the TAL of the loop of henle
Results:
- decrease intracellular Na, K, Cl in TAL
- decrease in back diffusion of K and positive potential
- decrease in reabsorption of Ca and Mg
- Increase in diuresis
Ion transport is virtually nonexistent
among the most efficacious diuretics available
Thiazide Diuretics
MOA: cause inhibition of the Na/Cl cotransporter (NCC) and block NaCl reabsorption in the DCT
Results:
- Increase luminal Na and Cl in DCT
- Increase diuresis
Enhance the reabsorption of Ca in both the DCT and PCT Largest class of diuretic agents
K+ sparring Diuretics, 2 kinds
in the collecting tubule
- most important site of K secretion
- site at which all diuretic induced changes in K balance occur (more Na delivered to collecting tubule leads to more K secretion)
Aldosterone (mineralcorticoid) receptor (MR) antagonist
- decreased expression of ENaC increasing Na excretion and increasing diuresis
- K excretion is decreased
- urine pH is increased and body pH is decreased
Na Channel ENaC inhibitor
- decreased activity of ENaC increasing Na excretion and increasing diuresis
- K excretion is decreased
- urine pH is increased and body pH is decreased
Urinary electrolytes levels, NaCl, NaHCO3, K, Body pH: Carbonic anydrase inhibitors
NaCl: increase
NaHCO3: big increase
K: increase
Body pH: decrease
Urinary electrolytes levels, NaCl, NaHCO3, K, Body pH: Loop agents
NaCl: big increase
NaHCO3: no change
K: increase
Body pH: increase
Urinary electrolytes levels, NaCl, NaHCO3, K, Body pH: THiazides
NaCl: increase
NaHCO3: increase
K: increase
Body pH: increase
Urinary electrolytes levels, NaCl, NaHCO3, K, Body pH: Loop agents plus thiazides
NaCl: big increase
NaHCO3: increase
K: increase
Body pH: increase
Urinary electrolytes levels, NaCl, NaHCO3, K, Body pH: K+ sparring agents
NaCl: increase
NaHCO3:slight increase
K: decrease
Body pH: decrease
what are factors affecting sodium reabsorption and secretion along the nephron
Na is secreted or reabsorbed in the late DT and cortical Collecting duct according to body needs
reabsorption: Na deciciency, low diet, hyponatremia, or Na loss through severe diarrhea
- Angiotensin II
- Aldosterone
SecretionL
- Increased ECF Na concentration
- Increased tubular flow rate
what are the factors affecting potassium reabsorbtion and secretion along the nephron
K is secreted or reabsorbed in the late DT and cortical collecting duct to the nees of the body
Most important factors that stimulate reabsorption:
- k deficiency, low K diet, hypokalemia
- K loss through diarrhea
Most important factors that stimulate potassium secretion
- increased ECF K
- aldosterone
- increased tubular flow
- Na delivery to cortical Collecting duct
