Renal Flashcards
Functions of the Kidneys
- Regulation of water, inorganic ion balance, and acid-base balance
- Removal of metabolic waste products from the blood and their excretion in the urine
- Removal of foreign chemicals from the blood and their excretion in the urine
- Production of hormones/enzymes:
a. Erythropoietin: hormone that controls erythrocyte production
b. Renin: enzyme that controls the formation of angiotensin and influences blood pressure and sodium balance
c. 1,25-dihdyroxyvitamn D: active vitamin that influences calcium balance.
Main physiological function of the kidney
Regulation of water, inorganic ion balance, and acid-base balance. e.x. removal of antibiotics. Urine will be smelly or change color.
Location of the kidneys
behind the peritoneum on either side of the cerebral column against the posterior abdominal wall
Whole renal system
Kidney –> Ureter –> Bladder –> Urethra.
Components of the Kidney
Renal Cortex, Renal Medulla, Renal Pelvis, Ureter (going out)
What the renal medulla structure is called
renal Pyramids
Role of renal Pelvis
where initial urine is followed through into the ureter.
Renal Artery
brings blood into the kidney
Renal Vein
Brings/drains blood out of the kidney
Interlobar artery
runs between the pyramid lobes
Arcuate artery
branches out towards the surface of the kidney into the cortex
Interlobular artery
supplies blood to the function unit of the kidney/specific part called the nephron.
How many nephrons in a single kidney
-each kidney contains ~1 mill subunits called Nephrons
Nephron consists of
Consists of
- Tubule
- Renal corpuslce: inside has a glomerulus (capillary loops) and bowmans capsule
Components in the Cortex
-glomerulus (glomerular capillaries)
-Bowmans Space in Bowmans capsule.
Above is all in the renal Corpuscle
Why long tube is called the tubule
it is a hollow tube surrounded by a mono layer of epithelial cells.
Renal corpuscle
combination of the glomerulus and bowman’s capsule
Bowmans Capsule(visceral layer)
epithelial cells that directly touch the glomerulus = visceral layer: podocytes)
Bowmans Capsule (parietal layer)
cells on the outside
Bowmans space
where first filtered urine is collected.
Glomerular Capillary Wall
- A lot of foot like processes that tightly interdigitate. Cells that do this are called podocytes.
Glomerular Capillary Wall (filtration barrier)
Filtration barrier consists of three parts: visceral glomerular epithelial cells (podocytes), glomerular basement membrane (GBM), and Endothelial Cells.
Fenestra
holes in the Lumen side of the layer of endothelial cells.
Path of blood filter in the capillary wall
Blood or plasma is filtered through the endothelial cells “windows” and through the light of the GBM. Then through the filtration slits to the bowmans space.
Function of glomerulus
to filter blood to make urine
Efferent arteriole
Carries blood away from the glomerulus
Afferent arteriole
Carries blood to the glomerulus
Three processes of urine formation
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
Glomerular Filtration
Filtration of plasma from the glomerular capillaries into Bowman’s space. Beginning of urine formation
Glomerular Filtrate
“Fluid in Bowmans space”, that is cell-free and except for proteins, contains all the substances in plasma in virtually the same concentrations as in plasma. There should be an absence of blood and big proteins.
Tubular secretion/absorption
As glomerular filtrate passes through the tubules, its composition is altered by movements of substance.
Tubules –> peritubular capillaries = Reabsorption
Peritubular capillaries –> tubules = Secretion
Amount Excreted =
Amount Filtered + Amount Secreted - Amount Reabsorbed
Excretion
fluid will leave the body
Secretion
fluid moving from the peritubular capillary to the tubule.
What is filtered by glomerular filtration
water and low-molecular weight substance
What is not filtered by glomerular filtration
cells, proteins(albumin, globulins), protein-bound substances(1/2 of calcium ion, fatty acids)
Forces involved in filtration
Favoring Filtration
-Glomerular capillary blood pressure (Pgc) 60 mmHg
Opposing Filtration
- Fluid pressure in Bowman’s space (Pbs) 15 mmHg
- Osmotic Force due to protein in plasma “Oncotic pressure” (piegc) 29mmHg
Net Glomerular filtration pressure
Pgc - Pbs - piegc(oncotic pressure) = 16 mmHg.
Higher force going into bowmans space. Net movement in that direction as well. Most important force that pushes filtration is Glomerular Capillary pressure
Glomerular Filtration Rate (GFR)
the volume of fluid filtered from the glomeruli into Bowman’s space per unit time.
What GFR is regulated by
- net filtration pressure
- membrane permeability
- surface area available for filtration
Normal GFR in 70 kg person
180L/Day (125ml/min)
Normal Blood Plamsa volume of this person is 3.5 L
180L/3.5 = 51.
Plasma is filtered 51x a day at glomeruli.
Decreased GFR
- Constrict Afferent Arteriole = lower pgc, decreased pressure favoring filtration
- Dilate Efferent Arteriole = blood flow goes up, less time for glomeruli to filter, less pressure for Pgc.
Increased GFR
- Constrict Efferent arteriole = more time for the glomeruli to filter, increase in pGC, favoring pressure for filtration
- Dilate Afferent Arteriole = increase in Pgc, favoring pressure for filtration
Filtered Load
-total amount of any freely filtered substance
FR = GFR x plasma concentration of the substance
e.g.
filtered load of glucose = 180 L/Day x 1 g/L = 180 g/day
net reabsorption
filtered load > amount excreted in the urine
Net secretion
filtered load
Transcellular
going through the epithelial cells
Paracellular
going in between cells
Tubular lumen
where the glomerular filtrate will travel through
Tubular epithelial
cells on the connected to the ouside of the tubular lumen.
Connected to each other via tight junction
Peritubular capillary
capillary that follows the tubular lumen. Provides nutrients to cells, also plays a big role in secretion and reabsorption
Important Facts about Tubular Reabsorption
- Filtered loads are enormous, generally greater than the amounts of the substance in the body
- Reabsorption of waste products is relatively incomplete (e.g. urea)
- Reabsorption of most useful plasma components (e.g. water, inorganic ions, and organic nutrients) is relatively complete.
- Reabsorption of some substances are not regulated (e.g. glucose, amino acids), while others are highly regulated (e.g. water, inorganic ions).
Two mechanism of reabsorption
diffusion and mediated transport
Reabsorption by diffusion
- often across the tight junctions connecting the tubular epithelial cells
Reabsorption by mediated transport
- occurs across tubular cells (transcellular epithelial transport)
- requires the participation of transport proteins in the plasma membrane of tubular cells. Usually coupled to the reabsorption of sodium.
Mechanisms of Solute transport
Passive: spontaneous, down an electrochemical gradient (no energy required)
- diffusion
- facilitated diffusion (channels, uniport. coupled transport(antiport or symport))
- Solvent drag
Active: against an e-c gradient (requires input of energy).
Uniport (facilitated diffusion)
allows only one chemical at a time, in one direction.
Transport Maximum
When the membrane transport proteins become saturated, the tubule can not reabsorb the substance any more, this limit is called transport maximum (Tm)
Tubular secretion
Tubular secretion moves substance from peritubular capillaries into the tubular lumen (opposite of reabsorption)
- mediated by the two mechanisms (diffusion and transcellular mediated transport)
- usually coupled to the reabsorption of sodium
- does not happen as often as reabsorption
Most important substance secreted by the tubules
hydrogen ion and potassium
In order to excrete waste products adequately
The GFR must be very large. Thus, the filtered volume of water and the filtered loads of all the nonwaste plasma solutes are also very large.
Division of Labor: proximal tubule
reabsorbs most of this filtered water and solutes. It is also a major site of secretion for various solutes, except K+
Division of Labor: Henle’s loop
also reabsorbs relatively large quantities of the major ions (less water)
Division of Labor: DCT/CD
volume of water and masses of solutes reaching here are relatively small. Fine-tuning. Determines the finals amounts excreted in the urine by adjusting the rates of reabsorption and in a few cases, secretion. Most homeostatic controls are exerted here.
DCT: Distal Collection Duct
CD: Collection Duct
Clearance
-Volume of plasma from which that substance is completely removed “cleared” by the kidneys per unit time.
Clearance of S(Cs) = Mass of S excreted per unit time/ Plasma Concentration of S (Ps)
Mass of S excreted per unit time = Urine Concentration of S (Us) x Urine volume per unit time (V)
Cs = UsV/Ps
Inulin Clearance
(not insulin) a polysaccharide that would be administered intravenously. It is freely filted at glomerulus but is NOT reabsorbed, secreted, or metabolized by the tubule. THus the clearance of inulin (Cin) is equal to the volume of plasma originally filtered (GFR).
Cin = GFR
Creatinine Clearance
Creatinine is a waste product produced by muscle.
It is filtered freely at glomerulus and is NOT reabsorbed
It is secreted at the tubule but the amount is small. It is NOT metabolized by the tubule. Thus, creatinine clearance is used as a clinical marker for GFR.
Clearance vs GFR
Clearance of Substance > GFR
- It is secreted at the tubule
Clearance of Substance
Where the majority of sodium and water reabsorption occurs(~2/3)
In the proximal tubule
Where the major hormonal control of reabsorption occurs
In the DCT and CD
What happens on the basolateral membrane
Active Na+/K+ -ATPase pumps transport sodium out of the cells and keep the intracellular concentration of sodium low. This allows for the high conc. of Na in the Tubular lumen to diffuse in naturally.
What happens on the apical(luminal) membrane
Sodium moves downhill from the tubular lumen into the tubular epithelial cells. Each tubular segment has different mechanisms.
e.g. In proximal Tubule: Na+ -H+ antiporter
Na+-glucose cotransporter
In CCD: diffusion via Na+ channel
Basolateral membrane
faces the peritubular capillary. Has a larger surface
Apical (luminal) membrane
faces the lumen of the distal tubule of collecting duct
What is sensing total body sodium.
Sodium is a major extracellular solute, thus changes in total body sodium result in similar changes in extracellular fluid volume
-Total body sodium is sensed as intravascular filling by baroreceptors in the cardiovascular system.
Sodium Excreted =
Sodium filtered - sodium reabsorbed
Sodium is NOT secreted in the tubules
Sodium Excretion is regulated by
- GFR (minor role)
2. Sodium Reabsorption (most important)
Renal Regulation of Sodium
Increase in Na+ and H2O loss due to diarrhea –> Plasma volume decreases –> Venous pressure decreases –> (Venous return, Atrial pressure, Ventricular end-diastolic vol, stroke vol, cardiac output all decrease) –> baroreceptors in the venous, atrial and arterial pic this up –> send signals via sympathetic nerves –> increase in constriction of the afferent arteriole –> decrease in net glomerulus filtration pressure –> decrease in GFR –> decrease in sodium and water excretion.
Aldosterone
steroid hormone secreted by the adrenal cortex, zona glomerulosa. Stimulates sodium reabsorption in the DCT and CCD.
Does NOT stimulate H2O reabsorption directly in the CCD.
Renin-Angiotensin System
Protein angiotensin in the blood, produced by liver –> converted into Angiotensin 1 by renin –> kidneys determine the amount of renin released –> effects the amount of Angiotensin 1 produced –> angiotensin 1 is converted to Angiotensin II almost automatically by an enzyme –> Angiotensin II stimulates the production of aldosterone in the adrenal gland –> Aldosterone is then release into the blood which stimulates the kidney –> Sodium and H2O reabsorption goes up –> excretion goes down.
Juxtaglomerular Cells
Cells that can secrete renin, sit tightly attached to the afferent arterioles.
Atrial Natriuretic peptide (ANP)
- a peptide hormone secreted by cells in the cardiac atria
- acts on the tubules to inhibit sodium reabsorption (opposite actions of aldosterone) and increases GFR.
- Increased total body sodium (thus increased extracellular fluid/plasma volume) stimulates ANP secretion.
- also inhibits Aldosterone secretion
Blood pressure influence on sodium excretion
increased blood pressure increases sodium excretion (pressure natriuresis)
Action of ANP
Plasma volume increase –> (Cardiac Atria ) distension and ANP secretion increase –> Plasma ANP increase –> Plasma Aldosterone decrease –> Afferent Arteriole dilated, Efferent Constriction (GFR increase) as well as decrease in Na reabsorption –> increase in sodium excretion
Hypoosmotic
Having total solute concentration less than that of normal extracellular fluid (300 mOsm)
Isoosmotic
having total solute concentration equal to that of normal extracellular fluid
Hyperosmotic
having total solute concentration greater than that of normal extracellular fluid
Maintenance of water ballance takes place in the CD, and there are two critical components
- High osmolarity of the medullary interstitium
2. Permeability of CD to water (regulated by vasopressin).
Properties of the Ascending limb
- actively reabsorbs NaCl
- impermeable water
Tubular fluid coming from the proximal tubule
Is always isoosmotic (300 mOsm)
Properties of the descending limb
- Does not reabsorb NaCl
- Permeable to water
Vasopressin
- peptide hormone, also called anti-diuretic hormone (ADH)
- produced by a group of hypothalamic neurons
- released from the posterior lobe of the pituitary gland
- couples to GPCR V1 (smooth muscle) and V2 (kidneys)
- Kidneys exclusively have V2
- stimulates the insertion of aquaporins in the luminal membrane of the collecting duct cells and increases the water permeability.
Presence and Absence of Vasopressin
- When present, collecting ducts become permeable to water –> water reabsorption
- When absent, collecting ducts become impermeable to water –> water diuresis
Diabetes Insipidus
causes by malfunction of the vasopressin system (vasopressin does NOT work)
Regulation of Vasopressin
- Osmoreceptor control (most important)
2. Baroreceptor control (less sensitive)
Hyperkalemia
high concentration of K in the extracellular fluid (>5 mEg/L)
Hypokalemia
Low concentration of K in the extracellular fluid (
Where is potassium excreted
- 90% excreted into urine
- 10% excreted into feces/sweat
Regulation of Potassium
- K is freely filtered at glomerulus
- Normally the tubules reabsorb most of this filtered K so that very little of the filtered K appears in the urin
- Unlike sodium or water, K can be secreted at the CCD
- Changes in K excretion are due mainly to changes in K secretion in the CCD (some in the DCT)
K secretion is coupled with
Na reabsorption due to the cotransporter in the epithelial cells of the tubular lumen.
Potassium secretion is regulated by
- Dietary intake of potassium
2. Aldosterone
Hyperaldosteronism
- condition in which the adrenal hormone aldosterone is released in excess
- caused by a benign tumor
- increased fluid volume, hypertension, hypokalemia. Renin is suppressed. Metabolic alkalosis is often seen.
Nonvolatile acids
Phosphoric Acid
Sulfuric Acid
Lactic Acid
Average net production: 40-80 mmol of H+ per day.
Buffer
Any substance that can reversibly bind hydrogen ions
Ultimate balance of H+ ions is controlled by
- Respiratory system (by controlling CO2)
- Kidneys (by controlling HCO3-) excretion of HCO3-
Both work together to minimize the change of H+ conc. (pH)
Renal Mechanism of H+ control via control of HCO3-
Low H+ conc. –> Kidneys excrete HCO3-
High H+ conc. –> Kidneys produce new HCO3- and add to the plasma.
Where reabsorption of HCO3-
Proximal tube is responsible for 80% of HCO3- reabsorption
How is addition of new HCO3- to the plasma achieved
- H+ secretion and excretion on nonbicarbonate buffers (such as phosphate)
- Glutamine metabolism with NH4+ excretion
Both processes could be viewed as H+ excretion by the kidney
Alkalosis
Low H+ conc. (high pH)
Acidosis
High H+ conc. (low pH)
Renal responses to Acidosis (high H+ conc.)
- Sufficient H+ are secreted to reabsorb all the filtered HCO3-
- Still more H+ are secreted and this contributes new HCO3- to the plasma as these H+ are excreted bound to non-HCO3- buffer such as HPO4 2-
- Tubular glutamine metabolism and ammonium excretion are enhanced, which also contributes new HCO3- to the plasma.
Net Result: More new HCO3- than usual are added to the plasma, thereby compensating for the acidosis. The urine is highly acidic (lowest attainable pH = 4.4)
Renal Responses to Alkalosis (low H+ conc.)
- Rate of H+ secretion is inadequate to reabsorb all the filtered HCO3-, so the significant amounts of HCO3- are excreted in the urine
- There is little or no H+ secretion on non-HCO3- urinary buffers
- Tubular glutamine metabolism and ammonium excretion are decreased, so that little or no new HCO3- is contributed to the plasma from this source.
Net Result: Plasma HCO3- will decrease, thereby compensating for the alkalosis. The urine is highly alkaline (pH >7.4)
Diuretics
- Drugs use clinically to increase the volume of urine excreted
- act on tubules to inhibit the reabsorption of sodium, along with chloride and/or bicarbonate, resulting in increased excretion of these ions, Water excretion increases too.
Loop Diuretics
- acts on the thick ascending limb of the loop of Henle.
- inhibits cotransport of sodium chloride and potassium
Potassium-sparing diuretics
- inhibit sodium reabsorption in the CCD, and also inhibits potassium secretion there. Thus unlike the other diuretics, plasma conc. of K does not decrease.
- either block the action of aldosterone or block the (aldosterone-regulated) epithelial sodium channel in the CCD
Treatment of Kidney Failure
- Hemodialysis
- Peritoneal Dialysis
- Kidney transplantation
