Renal physiology Flashcards
3 processes involved in urine formation:
- glomerular filtration
- selective reabsorption
- selective tubular secretion
What is a renal corpuscle?
Bowman’s capsule together with its contained glomerulus
what are podocytes?
specialized epithelial cells that make up the visceral lining of Bowman’s capsule, wrap around capillaries of the glomerulus
they form “filtration slits”
name the 2 predominant osmolytes in initial filtrate
sodium (Na+)
&
chloride (Cl-)
what is arginine vasopressin
another name for ADH (antidiuretic hormone)
regulates the tonicity of body fluids.
osmolality and osmolarity difference
Osmolarity: the number of solute particles per 1 L of solvent
Osmolality: is the number of solute particles in 1 kg of solvent
For dilute solutions, the difference between osmolarity and osmolality is insignificant.
osmolarity considers volume (L)
osmolality considers mass (kg)
ADH mechanism of action
Osmoreceptors detect increased plasma osmolarity ->
stimulates peripheral vasoconstriction +
the insertion of aquaporins into the luminal cells of the collecting ducts
what is diabetes insipidus
disorder of fluid imbalance
characterized by the lack of aquaporin channels in the distal collecting ducts from a lack of ADH (can also be from a lack of renal response to existing ADH)
water reabsorption prevented
osmolarity of the blood increases
osmoreceptors in the hypothalamus detect this change and stimulate thirst.
= polydipsia and polyuria cycle.
what is aldosterone
the major mineralcorticosteroid hormone from the adrenal cortex
major regulator of blood pressure because its essential for sodium conservation
promotes reabsorption of Na+
also promotes secretion of potassium
primary increase in bicarbonate ions indicates what type of state?
metabolic alkalosis
primary deficit in carbon dioxide indicates what type of state?
respiratory alkalosis
primary decrease in bicarbonate ions indicates what type of state?
metabolic acidosis
primary excess of carbon dioxide indicates what type of state?
respiratory acidosis
What is uric acid?
a waste metabolite from nucleic acid/purine/DNA/RNA catabolism
What is the juxtaglomerular apparatus?
function?
a specialized structure formed by the
distal convoluted tubule and the
glomerular afferent arteriole.
located near the vascular pole of the glomerulus
main function is to regulate:
blood pressure and the
glomerular filtration rate
Renin function
induces RAAS cascade resulting in the secretion of aldosterone in adrenal cortex layer of zona glomerulosa
more specifically it cleaves angiotensinogen into angiotensin I
calcitriol stimulates
stimulates intestinal calcium absorption,
increases reabsorption of calcium by the kidneys,
and possibly increases the release of calcium from skeletal stores.
thus increases blood calcium levels
aldosterone function
supports active reabsorption of sodium with associated passive reabsorption of water
and active secretion of potassium/ K+
primary mineralcorticoid is
aldosterone
Mineralcorticoid function
regulate water, Na, K and Cl balance and blood pressure
ADH secretion is controlled via?
regulated by osmolarity-sensitive cells in the hypothalamus, and pressure sensitive cells in
the circulatory system (sense volume of fluids)
A reduction in blood volume and blood pressure of 5-10% or more induces secretion of ADH.
Antidiuretic hormone (ADH), vasopressin main function
increases water reabsorption in distal tubules and the collecting ducts by regulating the density of aquaporins
Kidneys produce what hormones
erythropoietin
renin-angiotensin
vitamiin-D3-hormone/calcitriol
Plasma osmolarity of the body is monitored by
osmoreceptors in the hypothalamus, which
detect the concentration of electrolytes in the extracellular fluid.
polypeptide hormone ADH/vasopressin is produced and released where
The hypothalamus produces it,
then its transported to and released from the posterior pituitary
Where is aldosterone produced?
the outer layer of the adrenal cortex, the zona glomerulosa
what results in diabetes insipidus
Chronic underproduction of ADH or a mutation in the ADH receptor
how does aldosterone aid in maintaining proper water balance
by enhancing Na+ reabsorption and K+ secretion in Distal renal tubules.
Increases the number of Na+-K+-ATPase molecules.
The reabsorption of Na+ also results in the osmotic reabsorption of water, which alters blood volume and blood pressure.
Aldosterone release is stimulated by (3-5)
hypovolemia or decreased blood pressure
hyponatremia
hyperkalemia
Production stimulated by angiotensin II.
when is RAAS activated
When blood pressure drops. Detected by baroreceptors.
Where is renin produced and released
Produced by mesangial cells in walls of afferent arterioles of cells of the juxtaglomerular apparatus in response to decrease in perfusion pressure.
What is renin and what does it do
part of RAAS
an enzyme, circulates in the blood, reacts with a
plasma protein produced by the liver called angiotensinogen and produces angiotensin I
how is angiotensin I made
When angiotensinogen is cleaved by renin, it produces angiotensin I
what is angiotensin II and what does it do
part of RAAS
functions as a hormone, causing the release of aldosterone by the adrenal cortex,
resulting in increased Na+ reabsorption, water retention, and an increase in blood pressure.
Most powerful Na+ retaining hormone.
in addition to affecting aldosterone, what else does angiotensin II stimulate (3)
in addition to being a potent vasoconstrictor,
stimulates an increase in ADH and
increased thirst
what is a natriuretic peptide
circulating peptide hormones of cardiac origin that induce natriuresis, which is the excretion of sodium by the kidneys.
important in the regulation of intravascular blood volume and vascular tone.
what is ANP and where secreted
Atrial natriuretic peptide is secreted by atrial cardiac muscle cells
what is BNP and where secreted
Brain natriuretic peptide is secreted by ventricular cardiac muscle cells
name some natriuretic peptide functions (6)
increase urinary excretion of sodium,
increase GFR,
inhibit Na+ reabsorption in distal tubule and collecting duct,
inhibit secretion of renin, aldosterone and vasopressin,
decrease cardiac output,
inhibit sympathetic activity
What is inulin clearance?
procedure by which the filtering capacity of the glomeruli is determined by measuring the rate at which inulin, the test substance, is cleared from blood plasma.
descending limb of loop of henle permeable to what?
only water
ascending limb of loop of henle permeable to what?
ions: Na+ & Cl- & K+
approximate normal osmolarity of plasma
300 mOsm / L
milliosmoles per liter
explain countercurrent exchange
give example
is the transport of chemical metabolites between fluids moving in opposite directions separated by a permeable barrier such as blood within adjacent blood vessels flowing in opposite directions
such as between the vasa recta and loop of henle
Na+- K+ -ATPase moves how many of what, where, in or out?
3 Na+ out of tubular endothelium cell into peritubular capilllary, and 2 K+ into cell from renal interstitium so “bodyside”
How do some bacteria cause alkaline urine?
Bacterial urease generates ammonia from urea, elevating the pH of urine
furosemide mechanism of action
like other loop diuretics, acts by inhibiting the luminal Na-K-Cl cotransporter in the thick ascending limb of the loop of Henle
binds to the chloride transport channel, thus causing more sodium, chloride, and potassium to remain in the urine along with H2O
name 3 endocrine roles of the kidneys
- EPO synthesis (RBC production)
- Activation of vitamin D
- Control of blood pressure via the secretion of renin for the RAAS cascade
Name 5 metabolic waste products excreted via the kidneys
- Urea – metabolite of amino acids
- Creatinine – product of muscle creatine
- Uric acid – nucleic acids
- Bilirubin etc – haemoglobin breakdown
- Metabolites of hormones
In what part of the kidney is EPO produced?
erythropoietin is produced in the renal cortex by interstitial fibroblast-like cells that surround the renal tubules
In which part of the kidney are the loops of Henle, vasa recta and collecting
ducts located?
renal medulla
What portion of cardiac output do the kidneys receive?
20% (25% in some materials)
typical pressure in glomeruli
55mm Hg- 60 mmHg
typical pressure in the vasa recta
Vasa recta 13 mmHg
how does the parasympathetic NS affect the kidneys? vs
how does the sympathetic NS affect them?
Parasympathetic via CN X causes vasodilation of afferent arterioles,
increased blood flow -> increased urine production.
Sympathetic via renal nerves, noradrenaline & circulating adrenaline cause vasoconstriction of arterioles, reduction of blood flow into the glomerulus.
2 types of nephron
the functional unit of kidney
* Cortical
* Juxtamedullary
2 types of renal cortical interstitial cells
- Fibroblast-like cells – EPO production
- Phagocytic cells
4 roles of a nephron
- Filtration
- Secretion
- Reabsorption
- Excretion
How many times is t he entire plasma volume is filtered in a day
The entire plasma volume is filtered 60 times a day
the 3 layers to the “filtration barrier” of the glomeruli
- Endothelium
- Basement membrane
- Podocytes = visceral epithelium
Name the forces favoring filtration
Hydrostatic pressure of blood
(& ultrafiltrate oncotic pressure)
Name the forces opposing filtration
Hydrostatic pressure in Bowman’s capsule (approx. 15 mmHg)
Plasma oncotic pressure (approx. 30 mmHg)
The main difference between Osmotic Pressure and Oncotic Pressure
is that osmotic pressure is the pressure needed to stop the net movement of water across a permeable membrane which separates the solvent and solution
whereas oncotic pressure is the contribution made to total osmolality by colloids.
Define GFR
glomerular filtration rate is the amount of fitrate formed per minute by 2
kidneys
GFR depends on what 3 factors:
- Mean filtration pressure
- Permeability of the barrier
- Surface area
Main factors for regulation of GFR? (ca. 6)
Systemic blood pressure and renal blood flow
Systemic factor: RAAS
Intrinsic factors such as: myogenic reflex, tubuloglomerular feedback & endothelium-derived factors
what is renal myogenic reflex
The myogenic response is the reflex response of the afferent arterioles to changes in blood pressure.
Are part of the autoregulation mechanism which maintains a constant renal blood flow at varying arterial pressure.
What is tubuloglomerular feedback
Is one of several mechanisms the kidney uses to regulate GFR.
signal from the renal tubules is sent to the glomerulus in the event of increased distal tubular NaCl concentration. This signal triggers the constriction of affererent arterioles in juxtaglomerular apparatus, that ultimately brings GFR back to an appropriate level.
What are endothelium-derived factors in the context of the kidneys
endogenous substances that renal endothelial cells produce and release in response to various changes in body physiology
- Constrictors (thromboxane A2)
- Dilators (NO, prostacycline, PGE2)
Consequences of too high GFR
The filtrate passes through the nephron too fast and solutes (& water) do not get reabsorbed adequately.
- Urine output rises
- Risk of dehydration and electrolyte depletion
Consequences of too low GFR
too much volume get reabsorbed and waste products do not leave the body.
Main steps of RAAS
Angiotensinogen is activated by renin
The product angiotensin I which is converted by ACE
Angiotensin II causes:
Vasoconstriction
Aldosterone secretion is stimulated and Na+H2O retained
Vasoconstriction causes an increase in cardiac afterload
Na+H2O retention increases cardiac preload
What are the vasa recta?
Vasa recta are the special type of peritubular capillaries that wind around Henle loops.
Vasa recta receive water and solute added to the medullary interstitium by the nephron (just as the peritubular capillaries around the proximal an ddistal tubules also do).
What are the peritubular capillaries?
They surround the proximal and distal tubules.
Peritubular capillaries are the capillaries that arise from the efferent arteriole and feed the kidney with oxygen and nutrients.
They also receive reabsorbed water and solutes just like the vasa recta.
What does ACE enzyme do where?
Angiotensin converting enzyme converts inactive Ang I to active Ang II and degrades active bradykinin (BK), which play an important role in the control of blood pressure.
It is located mainly in the capillaries of the lungs but can also be found in endothelial and kidney epithelial cells.
How is GFR measured in practice (since inulin isn’t commonplace)
Creatinine concentration in plasma comparison to creatinine excretion in urine
(e.g. UPC – urine protein-creatinine ratio)
Most reabsorption occurs in
proximal tubules
where is urine concentrated
Loop of Henle
&
finally concentrating portion are the collecting ducts
what pathways are available for transport in the nephron
Transcellular pathway
Paracellular pathway
name the 5 Mechanisms of transport occuring in the nephron
- Simple diffusion
- Simple facilitated diffusion
- Primary active transport
- Secondary active transport
- Endocytosis
describe Passive transport
Simple diffusion – driven by concentration gradient
describe Active transport
Uses ATP-energy: active pumps
Co-transport (solvent drag):
water moves alongside the actively transported molecules
what is Tubular secretion
Transfer of substances from peritubular capillaries to tubular lumen via
* Passive diffusion, active transport.
- Typically waste products (creatinine, NH4+, urea), some ions (H+, K+),
hormones and toxins
Proximal convoluted tubule
location and Main functions
In the cortex
- Main functions
Reabsorption (glucose, ions (very permeable to Na+), H2O, aminoacids)
Secretion (excessive substances; toxins, drugs)
How much of what does the Proximal convoluted tubule reabsorb?
- 65 % water
- 65 % NaCl
also Reabsorbs
* Na+, K+, Ca++, PO43-, Glu, amino acid
How much of what does the loop of henle reabsorb?
which limb reabsorbs what?
25% Nacl
15 % H2O
- Decending: H2O
- Ascending: NaCl
no active transport in thin segements
Distal convoluted tubule – or „diluting segment“
function?
called diluting because it removes ions from the filtrate
Includes the juxtaglomerular apparatus (renin production)
Functions: Reabsorption, secretion
- Is Not permeable to water
- Regulates K+, Na+, Ca++, H+, Cl-
- pH (HCO3- and H+)
- Ca++ reabsorption via parathyroid hormone
Collecting duct function
other than the obvious:
participates in electrolyte and fluid balance through reabsorption and excretion
(Cl-, K+, H+, HCO3-)
Are largely impermeable to water without the presence of antidiuretic hormone (ADH, or vasopressin).
Which hormones act on the collecting ducts?
- Aldosterone
- Antidiuretic hormone (ADH) = vasopressin
- Natriuretic peptides
where does ADH come from in reponse to what
Its produced in the hypothalamus but released from the posterior pituitary in response to hypertonicity and causes the kidneys to reabsorb solute-free water.
what is the effect of NO released in the kidneys
Nitric oxide
* Gas produced in endothelial and epithelial cells
* Increases renal water excretion and Na+ uptake
what is the effect of Endothelin-1 released in the kidneys
Produced in collecting duct
- Increases NaCl and water excretion
what is the effect of ANP released in the kidneys
Atrial natriuretic peptide
- Produced in atria by distension
- Inhibits aldosterone and renin
primary site of action of antidiuretic
hormone
Collecting duct
proportion of Na+ lost in sweat and faeces
5% loss
normal plasma concent. of Na+
135-145 mmol/l
What is used to reabsorb Na+?
Na+-K+-ATPases (Sodium–potassium pumps)
on the basolateral membrane of all Na-reabsorbing cells
What do the sodium-potassium pumps generate?
Generates Na+ gradient between tubular filtrate and the internal environment of the cell
What does the Na+ gradient generated by teh Na+-K+ pumps cause?
causes Na+ to enter the cell passively at apical membrane
using ion channels or transporters
functional differences between loop of henle thin and thick segments
Thin segments
* No active transport
* Descending permeable to H2O
* Ascending permeable to Na+
Thick ascending limb
* Active transport of Na+
* Na+-K+-2Cl
* Uses Na+ gradient
* K+ re-enters
Explain which direction H2O and NaCl go in the ascending limb of loop of henle (countercurrent exchange)
Descending capillaries here so,
* Water diffuses out of blood
* NaCl diffuses into blood
Explain which direction H2O and NaCl go in the descending limb of loop of henle (countercurrent exchange)
Ascending capillaries here so,
* Water diffuses into blood
* NaCl diffuses out of blood
how much is reabsorbed in the distal convoluted tubule?
5% Na+ & Cl
(Na+-Cl–cotransporter on apical membrane)
how much is reabsored in the collecting tubules?
2-5%
what are principal cells and intercalated cells?
principal cell is the major cell type in the initial collecting tubule and the cortical and outer medullary collecting ducts, accounting for approximately two-thirds of the cells in most regions.
Intercalated cells account for the remainder of the cortical and outer medullary collecting duct cells.
What do type B intercalated cells do?
Type B intercalated cells do not have Na+-K+-ATPase.
Instead they have H+-ATPase in the basolateral plasma membrane so they generate a H+ gradient
regulation of acid-base homeostasis (they secret bicarbonate at the apical membrane)
What do principal cells do?
sodium and water reabsorption alongside potassium secretion
aldosterone increases the activity of Na+-K+-pumps in these cells
What is the difference between aldosterone and ADH?
ADH directly increases the tubules’ reabsorption of water by opening pores in the epithelial cells of the kidneys,
whereas aldosterone indirectly increases the water reabsorption of the tubules by creating an osmotic pressure through increasing the activity of sodium pumps.
what plasma concentration of Na+ constitutes hyponatremia?
symptoms?
mild 131–135 mmol/L
severe <115 mmol/L
Due to swelling of the cells (cerebral edema) confusion, seizures, coma
Normal intracellular K+ concentration?
IC 150mmol/l
Normal extracellular K+ concentration?
EC 4mmol/l
How much K+ is reabsorbed in prox. con. tubules?
& loop of henle?
65% of the filtered K+ reabsorbed in proximal tubule
20% reabsorbed in Loop of Henle
Only very small proportion reaches distal nephron
How does K+ move in the prox. con. tubule?
- No specific K+ channels
- Primarily passive movement
- Paracellular pathway
- Linked to Na+ and H2O reabsorption:
The reabsorption of Na+ causes H2O reabsorption and - K+ flows freely with water
Describe K+ handling in Thick ascending limb of loop of henle
30% of K+ reabsorbed here
- Na+/K+-ATPase on basolateral membrane pumps Na+ out into the bloodstream which creates gradient for NKCC2 cotransporter
- NKCC2-transporter – on apical membrane (1 na + 1 k + 2 cl in together)
- is also paracellular mechanism
What is NKCC2
Na-K-Cl cotransporter, secondary active transport.
the 2 stand for which isoform it is as there are at least 2 types of this cotransporter
NKCC2 resides in the apical membrane and transports Na+, K+, and Cl- across the cell membrane in the same direction.
Maintains electroneutrality by moving two positively charged solutes (Na & K) alongside two parts of negatively charged solute (Cl).
1Na:1K:2Cl.
Describe K+ handling in distal conv. tubule
K+ reabsorption is Na-dependent and passive
Describe Renal K+ reabsorption in the collecting tubules
10-12% K+ reabsorption when trying to conserve it
the principal cells in this part secrete K+
aldosterone increase K+ secretion (simultaneously with increasing Na+ absorption)
the intercalated cells here reabsorb K+ by way of
* Apical H+-K+-ATPase mediates movement of H+ into the lumen, driving K+ into the cell
* Basolateral K+ channels allows leakage to bloodstream
Describe Renal K+ secretion in the collecting tubules
K+ secretion occurs mainly in collecting duct via principal cells
- ENaC on the apical membrane
- Na+/K+-ATPase on basolateral membrane
*Rate of secretion variable
* Up to 15-20% if high K+ diet
* Minimal if body is deprived of K+
What is ENaC
The epithelial sodium channel (ENaC) that is selectively permeable to sodium ions (Na+).
is involved primarily in the reabsorption of sodium ions via the apical membrane in the collecting ducts
The activity of ENaC is modulated by aldosterone.
Name 4 major factors affecting Renal K+ secretion
High extracellular K+ concentration
Aldosterone
Acidosis
Alkalosis
How does
high extracellular K+ concentration
affaect renal K+ secretion?
High extracellular K+ concentration
stimulates Na+/K+-ATPase,
Increases permeability of K+ channels
which both cause increased K+ secretion
How does Aldosterone stimulate K+ secretion?
Aldosterone stimulates Na+/K+-ATPase
which in turn stimulates K+ channels and ENaC on basolateral membrane
which both increase K+ secretion
How does acidosis affect K+ secretion?
Acidosis causes an increased H+ secretion into lumen to correct acidosis
- Due to H+/K+-ATPase pump,
when H+ is secreted into lumen, K+ is driven back into the cell,
leading to decreased K+ secretion
How does alkalosis affect K+ secretion?
Alkalosis causes the kidneys to try to decrease H+ secretion, increasing secretion of K+ (because of the H+/K+ pumps)
- this stimulates Na+/K+-ATPase, leading to increased K+ channel
permeability
thus increased K+ secretion
what plasma concentration of K+ constitutes hypokalemia?
symptoms?
< 3.5mmol/L
- Altered cardiac excitability – arrhythmias
- Gastrointestinal, neuromuscular
dysfunction – paralytic ileus - Skeletal muscle weakness
what is the difference between hypovolemia & dehydration
Reduction of circulating volume – hypovolemia
Reduction of cellular water – dehydration
In which parts of a nephron does water not move freely via osmosis?
Ascending limb – not permeable to water
Distal tubules – low water permeability
Collecting ducts – ADH dependent water movement
How do the kidneys regulate acid base balance
Kidneys regulate blood pH by excreting H+ and
reabsorbing HCO3-
Where and how does most H+ secretion occur in the kidneys?
Most of the H + secretion occurs in the proximal convoluted tubule in exchange for Na+
Antiport mechanism: moves Na + and H + in opposite directions
What proportion of calcium is ionized/free in plasma?
50%
What proportion of calcium is bound to plasma proteins in plasma?
40%
What proportion of calcium is complexed with anions in plasma?
10% complexed with anions (phosphate, citrate etc.)
how is acidosis related to plasma ca2+?
The binding of Ca+ to blood proteins is pH dependent and so alters the level of ionized calcium in the blood.
An increase in pH, alkalosis, promotes increased protein binding, which decreases free/ionized calcium levels. Alkalosis thus can cause hypocalcemic tetany.
Acidosis, on the other hand, decreases protein binding, resulting in increased free calcium levels.
Main Ca++ regulating hormone
parathyroid hormone (PTH)
What stimulates PTH
Production stimulated by hypocalcemia
As the blood filters through the parathyroid glands, they detect the amount of calcium present in the blood and react by making more or less parathyroid hormone (PTH).
What does PTH cause?
- PTH causes release of Ca++ from bones
- Also increases intestinal uptake (stimulation of Vit D3 activation)
How much Ca+ absorption occurs in the small intestine?
25-30% of dietary calcium
How much Ca2+ and how is it reabsorbed in the prox. conv. tubule?
65% reabsorbed in proximal tubule
- Paracellular and passive reabsorption
How much Ca2+ and how is it reabsorbed in the thick ascending loop of Henle?
20% in thick ascending loop of Henle
* Paracellular and passive
How much Ca2+ and how is it reabsorbed in the distal conv. tubule?
10% distal convoluted tubule
* Active transcellular (Ca++ATPase)
* Hormonal control
How is Ca2+ reabsorbption regulated in the distal conv. tubule?
By PTH, calcitriol & calcitonin
where is calcitonin produced in response to what?
secreted by parafollicular cells (also known as C cells) of the thyroid based on blood ca2+ levels
What’s the diff between cortical and juxtamedullary nephrons?
Cortical nephrons have a glomerulus located nearer to the outer parts of the cortex and their loops of Henle are short.
Juxtamedullary nephrons have a glomerulus near the junction of the cortex and medulla and their loops of Henle penetrate deep into the medulla.
what is referred to as the dilution segment of a nephron?
distal convoluted tubule
What is urea?
nitrogenous waste metabolite from protein catabolism
The main driving force for the reabsorption of solutes from
the tubule fluid is:
Active transport of Na+
from the tubule epithelial cell
across the basolateral plasma membrane by the Na+,K+-ATPase pump
The ultimate rate of excretion of K+ in the urine is determined by the:
Collecting duct, where the principal cells are capable of
K+ secretion, and the intercalated cells are capable of K+ reabsorption
The bulk of filtered water is reabsorbed by which renal tubule
segment?
technically Proximal tubule most
2nd place, descending thin limb of Henle’s loop
The hypertonic medullary interstitium is generated in large
part by
Active reabsorption of Na+ by the water-impermeable,
thick ascending limb of Henle’s loop
The bulk of acid secretion (bicarbonate reabsorption) is
accomplished by which renal tubule segment?
Proximal tubule
Which renal tubule segment determines the ultimate ph of the urine?
The collecting duct determines the ultimate pH of the
urine
The glomerular filtration rate (GFR) is the:
Volume of glomerular filtrate formed by the kidneys per
minute per kilogram of body weight.
In clinical practice the GFR is often estimated by determining
the rate of creatinine clearance.
The rate of creatinine clearance is the:
Volume of plasma cleared of creatinine per minute per
kilogram of body weight
The two major characteristics that determine whether a blood
component is filtered or retained in the capillary lumen are its
Molecular radius and electrical charge
How does the Activation of the renin-angiotensin-aldosterone system affect GFR
GFR increases with increased blood pressure
