Renal System Flashcards
Functions of the kidney?
- 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 feoreign chemicals from the blood and their excretion in the urine
- Production of hormones/enzymes
Erythropoietin?
Produced at the kindeys, it is a hormone that controls erythrocyte production for formation of RBCs
Renin?
Produced at the kidneys, it is an enzyme that ontrols the formation of angiotensin and influences blood pressure and sodium balance
1,25-dihydroxyvitamin D?
The active form of vitamin D that is formed by the kidney and influences calcium balance
T/F: Kidneys are paired organs ?
True
How much do kidneys weight approx.?
150 grams each
Where in the body are kidneys found?
Behind the peritoneum(epithelial layer of the abdominal cavity) on either side of the vertebreal column against the posterior abdominal wall(close to the back)
What does renal mean?
Pertaining to the kidneys
How are kidneys connected to the bladder?
Kidneys are connected to the bladder via the ureters, urine is then held in the bladder and then emptied via the urethra
Can people with one kidney survive?
Yes, they are normally healthy individuals
Vasculature of the kidney?
-The kidneys have one renal artery entering the kidney
-The kidneys have one renal vein
Layers of the kidney from outside in?
- Renal cortex
- Renal medulla
- Renal pelvis(urine formation)
Branching of the renal artery in the kidney in order?
- Renal artery
- Interlobar artery
- Arcuate artery
- Interlobular artery
- Afferent arteriole
When does the interlobar artery start?
Goes between the medulla
When are the arcuate arteries found?
When the interlobar artery reaches the junction between the cortex and the medulla, the arcuate artery starts and branches out perpendicularly
When do the interlobular arteries start?
They branch out from the arcuate arteries into the renal cortex
Afferent arterioles?
-Comes from the interlobular artery and brings blood to the nephron
Where are nephrons found?
In the renal cortex attached to afferent arterioles
How nephrons does each kidney have?
1 million
What is a nephron composed of?
- Tubule
- Renal corpuscle which is made of two parts(glomerulus(capillary loops) and bowman’s capsule)
Describe the renal corpuscle?
-Outer layer of the Bowman’s capsule (parietal layer)
-Bowman’s Space
-Inner layer of the Bowman’s capsule (visceral layer: podocytes)
-Glomerulus: entangled in capillary loops
Afferent vs Efferent Arteriole?
Afferent arteriole: Feeds blood into the capillary loop of the glomerulus
Efferent arteriole: Blood exits the capillary loops via this
Distal tubule of the glomerulus?
This is where the loop of Henle attaches to the glomerulus
Podocytes?
-Specialized epithelial cells of the visceral layer of the bowman’s capsule
-Surround the capillary walls
-Have foot processes that interdigitate with one another and surround the capillary wall
3 components of the capillary wall?
- Visceral glomerular epithelial cells(podocytes)
- Glomerular basement membrane
- Endothelial cells
Endothelial cells?
Line the capillaries and are fenestrated
Role of the glomerulus?
To filter blood and make urine
How much blood do kidney’s receive?
They recieve 20% of the cardiac output which is about 1 litre per minute
Peritubular Capillaries?
The efferent arteriole branches out of the glomerulus and surrounds the tubulules forming the peritubular capillaries
Function of the peritubular capillaries?
Reabsorb things from the lumen of the tubule that were filtered by the kidneys
Three processes of urine formation?
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
What is glomerular filtration?
-The beginning of urine formation where the plasma is filtered from the glomerular capillaries lumen into the Bowman’s space
Where is the glomerular filtrate located?
Bowman’s space
What things are found/not found in the glomerular filtrate?
-Glomerular filtrate is cell-free and protein free
-Contains small things such as H2O and ions in virtually the same concentrations as in the plasma
Tubular secretion?
As the glomerular filtrate passes through the tubules, its composition is altered by movements of substances
Reabsorption?
When things go from the tubular lumen to the peritubular capillaries
Secretion?
When things go from the peritubular capillaries to the tubule lumen
Excretion vs Secretion?
Excretion: Final elimination into urine
Secretion: Movement from peritubular capillary into the tubule lumen
How is the amount of urine secreted determined?
Amount filtered + Amount secreted - Amount reabsorbed = Amount secreted via urine
How are sodium and water secreted?
- Some is filtered via glomerular filtration
- Majority is reabsorbed into the capillary
- Only a fraction is excreted into the urine
Most common type of secretion
How is glucose secreted?
- Some is filtered via glomerular filtration into the tubule lumen
- All of it is reabsorbed
- No glucose in the urine (if you do it is a sign of disease)
How is Para-amino-hippurate secreted?
- Filtered via glomerular filtration into the tubule lumen
- More is secreted into the tubule lumen
- All of it is secreted into the urine
It is entirely eliminated in the urine
T/F: The rate of filtration, reabsorption, or secretion is subject to physiological control?
True
What happens if you increase your water intake?
If a normal person drinks lots of water, reabsorption of water is decreased and excess water will be excreted into the urine
Homeostatic mechanism of the kidneys?
When the body content of a substance goes above or below normal, homeostatic mechnisms can regulate the substance’s bodily balance by changing these rates
Name the consecutive segments of the nephron?
- Renal Corpuscle
- Proximal tubule
- Loop of Henle
- Distal convoluted tubule
- Collecting duct
Proximal tubule?
-Proximal = close to the glomerulus
Starts in the cortex then goes down into the medulla
Loop of Henle?
- Descending thin limb(medulla)
- Ascending thin limb(medulla)
- Thick ascending limb(medulla then goes to attach to the glomerulus in the cortex)
Distal convoluted tubule?
- Found in the cortex
Collecting duct?
- Cortical collecting duct(cortex)
- Medullary collecting duct(medulla)
These attach neighbouring nephrons
What can be freely filtered by the glomerulus and are found in the filtrate?
Water, Low-molecular weight substances
What substances cannot be filtered by the glomerulus and remain in the plasma?
- Cells
- Proteins(ex. albumin, globulins)
- Protein-bound substances(ex. 1/2 of calcium ions are bound to proteins, fatty acids)
Forces favouring filtration into the Bowman’s Space?
Glomerular capillary blood pressure(Pgc)
Forces opposing filtration into the Bowman’s Space?
- Fluid pressure in the Bowman’s space(Pbs)
- Osmotic force due to protein in plasma (pi GC)
Osmotic force due to protein in plasma?
Within the capillary proteins are not filtered which pulls water back into the capillary from the tubular lumen
Net glomerular filtration pressure equation?
PGC - PBS - piGC
What is the Glomerular filtration rate(GFR)?
The volume of fluid filtered from the glomerulus into the Bowman’s space per unit time
What three factors regulate the GFR?
- Net filtration pressure
- Membrane permeability(physiological)
- Surface area available for filtration(physiological)
Normal GFR for a 70kg person?
180L/day
Normal plasma volume of 70kg person?
5% of the body weight thus 3.5L
How many times is plasma filtered per day on average in 70kg person?
51 times (180/3.5)
How can GFR be decreased?
- Constriction of the afferent arteriole (this decrease blood flow which decrease pressure in the glomerular capillary)
- Dilation of the efferent arteriole (this increases blood flow out of the glomerular capillary which decreases pressure in the glomerular capillary)
How can GFR be increased?
- Constriction of the efferent arteriole (Builds up pressure in the glomerular capillary because less blood can exit)
- Dilation of afferent arteriole(more blood flow into the glomerular capillary increases pressure + GFR)
Filtered load?
Total amount of any freely filtered substance
How to calculate filtered load?
GFR X plasma concentration of the substance
What does it mean when the filtered load is greater than the amount excreted in the urine?
The substance must be reabsorbed into the peritbular capillary. There is net reabsorption
What does it mean when the filtered load is less than the amount excreted in the urine?
The substance must be excreted into the tubular lumen. There is net secretion.
Paracellular reabsorption?
Reabsorption that occurs between cells through tight junctions
Transcellular reabsorption?
Reabsorption that occurs through tubular epithelial cells
Basolateral membrane?
Faces the peritbular capillary
Apical membrane/Luminal membrane?
Faces the tubule lumen
What separates the luminal membrane from the basolateral membrane?
Tight junctions, these can have varying permeability (some are very tight others allow things to pass through)
T/F: Filtered load it typically large but excretion is small?
True, this is because of reabsorption
T/F: Filtered loads are generally greater than the amounts of substance in the body?
True
Reabsorption of waste products?
Relatively incomplete (ex. urea, potassium)
Reabsorption of the most useful plasma components(water, inorganic ions, and organic nutrients)?
Relatively complete
Reabsorption of what substance is not regulated vs highly regulated?
Reabsorption of glucose and amino acids is not regulated (they are completely reabsorbed)
Reabsorption of water and inorganic ions is highly regulated
Two mechanisms of reabsorption?
Diffusion
Mediated transport
Where does reabsorption via diffusion typically occur?
Across the tight junctions connecting tubular epithelial cells(paracellularly)
How is urea reabsorbed?
- Urea is freely filtred at the glomerulus
- In the PT, water reabsorption occurs this gives rise to a high concentration of urea in the tubular fluid which creates a gradient for urea to diffuse into the ISF and eventually into the peritubular capillaries
Where is urea reabsorbed?
Proximal tubule
Where does reabsorption via mediated transport typically occur?
Must occur transcellularly(across tubular epithelial cells) because it requires transport proteins in the plasma membrane
What is mediated transport typically coupled to?
The reabsorption of sodium
Na+/K+ ATPase mechanism?
On the basolateral membrane of the tubular epithelial cells there is a Na+/K+ ATPase that pumps Na+ out of the cell and pumps K+ into the cell
How is the Na+ concentration in the cells so low?
Due to the Na+/K+ ATPase pumping sodium outside of the cell and into the peritbular capillary
Co-transporters found on the apical membrane of the tubular epithelial cells?
- Glucose/Na+ co-transporter
- Amino acid/Na+ co-transporter
How does the Glucose and amino acid co-transporters work?
The low concentration of Na+ in the epithelial cells creates a concentration gradient from the tubular lumen to the cell. When Na+ is drive by the concentration gradient into the cells the co-transporters bring glucose and amino acid into the cells increase their concentration in the cells
How are glucose and amino acids transported to the peritubular capillary?
Glucose and amino acid transporters are found on the basolateral membrane of the tubular epithelial cell and transport glucose and AA into the ISF and eventually into the peritubular capillary
Is mediated transport active or passive?
Co-transport : passive
ATPase: active
Transport maximum(Tm)?
When the membrane transport proteins become saturated, the tubule can not reabsorb the substance anymore
Is Tm met in healthy individuals?
NO
When is Tm met?
In people with disease(insulin deficiency/resistance)
Explain transport maximum in individuals with diabetes mellitus?
The plasma concentration of glucose can become very high and the filtered load of glucose exceeds the capacity of the tubules to reabsorb glucose(transport maximum reached). Now urine will contain glucose because not all glucose will be reabsorbed(glucosuria).
Tubular secretion mediated by what two mechanisms?
- Diffusion
- Transcellular mediated transport
Most important substances secreted by the tubules?
Hydrogen ions and potassium
T/F: Tubular secretion is usually coupoled to the reabsorption of sodium?
True
Why do the tubules divide up labor?
Because the filter load is so enormous and the tubules have to do a lot of reabsorption and even some secretion
What does the proximal tubule reabsorb/secrete?
Reabsorbs most of the filtered water and solutes
Secretes various solutes, except not K+
What does the Loop of Henle reabsorb/secrete?
Reabsorbs relatively large quantities of the major ions (less water)
What does the DCT/CD reabsorb/secrete?
Fine-tuning
Determines the final amounts excreted in the urine by adjusting the rate of reabsorption, and, in a few cases secretion.
Most homestatic controls are exerted here.
What part of the tubule recieves a small volume of water and masses of solutes?
The DCT/CD
What is clearance?
The volume of plasma from which that substance is completely removed by the kidneys per unit time
How is clearance calculated?
(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)
Overall equation for clearance?
Cs = UsV/Ps
What is inulin and how does it react in the body?
Inulin is a polysaccharide that is administered intravenously
It is freely filtered at the glomerulus, not reabsorbed, secreted or metabolized by the tubule
What does the clearance of inuline represent?
It is the most accurate marker of GFR
Cin = GFR
Why is inulin difficult to use?
- Must infuse the person with inulin at a constant rate to maintain a specific concentration in the plasma
-Person must collect urine constantly over 24 hours
Why is inulin used?
To determine the GFR of a person
What is creatinine and how does it react in the body?
A waste product produced by muscle
It is freely filtered at the glomerulus and NOT reabsorbed or metabolized but it is secreted at the tubule but the amount is negligible
What is creatinine used for?
A marker for GFR
What is it better than inulin?
Dees not require constant IV because it is produced by the body at a constant rate
Patient just need to collect urine for 24 hours
Creatinine clearance calculation?
Creatine clearance = (Ucr(urine concentration of creatinine) X V(urine volume))/Pcr(plasma concentration of creatinine)
Clearance vs GFR?
Clearance: unique to a substance/molecule
GFR: unique to a person
What does it mean if the clearance of a substance is greater than the GFR?
The substance must have net secretion at the level of the tubule
What does it mean if the clearance of a substance is less than the GFR?
The substance must have net reabsorption at the level of the tubule
When is clearance less than GFR?
In cases of incomplete(Na+) and complete (glucose) reabsorption
When is clearance greater than GFR?
In cases of secretion where the substance is cleared from the blood (ex. para-amino-hippurate)
What is a marker of renal plasma flow?
PAH(secretion)
Why does total-body balance of Na and Water need to be maintained ?
To sustain blood pressure + life
In what three ways do we intake water daily?
- Liquids
- Food
- Metabolically produced
What contributes to the largest amount of water intake?
In via liquids
In what four ways do we output water daily?
- Insensible loss(skin and lungs)
- Sweat
- Feces
- Urine
What 2 ways are minimum outputs of water?
Via feces and sweat
Largest output of water via?
Urination(also only regulatable part)
How do we intake sodium daily?
Via food
How do we output sodium daily?
- Sweat
- Feces
- Urine
What part of sodium output is regulatable?
Excretion of sodium in urine is regulatable in sweat and feces sodium loss should be minimal
Should sodium and water intake and output be equal?
Yes, we are always in water and sodium balance in physiological conditions
How much can water output vary?
Depending on intake water output can vary from 0.4L/day to 25L/day
How much can sodium output vary?
Depending on intake sodium output can vary from 0.05 g/day to 25 g/day
Are sodium and water secreted?
No, they are 99% reabsorbed
Where does the majority of sodium and water reabsorption occur?
2/3 of the reabsorption occurs in the proximal tubule
Where does the major hormonal control of sodium and water reabsorption occur?
In the distal convoluted tubule and the collecting duct(near the end of the nephron)
Is sodium reabsorption an active process?
Yes, it requires energy
Where does sodium reabsorption occur?
In all tubular segments except the descending thin limb of the loop of Henle
How does water reabsorption occur?
Via passive diffusion (osmosis) and it is dependent on sodium reabsorption
Describe the active process of sodium reabsorption?
- Na+/K+ on the basolateral membrane pumps Na+ into the ISF and K+ into the tubular epithelial cell
- This lowers the Na+ concentration in the cell(intracellular) which creates gradient from the tubular lumen into the epithelial cell.
- Na+ diffuses from the tubular lumen into the cell and K+ diffuses into the tubular lumen via luminal membrane
- The Na+ that enters the ISF is reabsorbed into the peritubular capillary
How is sodium transported from the tubular lumen into the epithelial cells in the PT?
In the proximal tubule there are multiple mechanisms.
1. Antiporter(two molecules move in opposing directions ex. Na+ moves into the cell and H+ moves into the tubular lumen)
2. Cotransporter(two molecules move in the same direction. Ex. Na+ and glucose)
Are cotransporters and antitransporters active transport?
Yes, because they use the energy generated by an electrochemical gradient
How is sodium transported from the tubular lumen into the epithelial cells in the cortical collecting duct?
Via diffusion through an Na+ channel
How does the body maintain sodium balance?
When you increase sodium intake, urinary excretion of sodium increases
When you decrease sodium intake, urinary excretion of sodium decreases
Sodium is a major extracellular solute, how can the body sense changes in sodium?
Since sodium is the major extracellular solute when sodium concentrations change in the body similar changes occur in the extracellular fluid volume
Total body water percentage?
About 60%
ICF vs ECF of total body water?
Intracellular fluid : 40% of total body water
Extracellular fluid: 20% of total body water
What makes up the extracellular fluid?
3/4(15%) Interstitial fluid(between vasculature)
1/4(5%) Plasma(within the vasculature)
How is total body sodium sensed?
Vessels in the body have baroreceptor on them that detect sodium changes due to increases/decreases in intravascular filling by plasma
T/F: Plasma concentration of sodium is a marker for total body sodium?
False, Na+ is sensed by vascular filling of plasma not by Na+ concentration in the plasma
What does plasma concentration of sodium indicate?
The relative relationship of total body Na and water
How is sodium excreted calculated?
Sodium excreted = sodium filtered - sodium reabsorbed (NO sodium secreted)
How can sodium excretion be regulated?
- GFR(minor role), changes sodium filtered
- Sodium reabsorption (most important), changes sodium reabsorbed
How is sodium excretion regulated by GFR via venous baroreceptors?
- Loss of Na+ causes a decrase in plasma volume and venous pressure this acticate the baroreceptors of the venous system (sense underfilling). The baroreceptors send a signal to the renal sympathetic nerves innervating the kidneys which causes constriction of the a.a which decreases net GF pressure and decreases GFR resulting in less Na+ being excreted
How is sodium excretion regulated by GFR via atrial baroreceptors?
Loss of Na+ causes a decrase in plasma volume and venous pressure this results in less venous return and a drop in atrial pressure.
The drop in atrial pressure is sensed by baroreceptors in the atrial and it to send signals to the sympathetic nerves innervating the kidneys has same effects as venous.
How is sodium excretion regulated by GFR via arterial baroreceptors?
Loss of Na+ causes a decrase in plasma volume and venous pressure this results in less venous return and a drop in atrial pressure which leads to lower ventricular end-diastolic volume. lower stroke volume and lower CO. This leads to lower arterial blood pressure which leads to underfilling which is sensed by baroreceptor.
How does lower arterial BP have a direct effect on GFR?
When arterial BP decreases, the renal artery pressure goes down which leads to decreased pressure in the afferent arteriole which decreases GF pressure and thus decreases GFR resulting in less excretion of Na+
Key hormone that regulates sodium reabsorption?
Aldosterone
What is aldosterone?
A steroid hormone secreted by the adrenal cortex
What does aldosterone do?
Stimulates sodium reabsorption in the DCT and CCD
How does the filtered load change depending on the presence of aldosterone?
No aldosterone(salty environment): ~2% of filtered load is excreted(up to 35g of sodium)
Aldosterone(barely any salt in environment): ~0% of filtered load is excreted(almost all reabsorbed)
Percentage of Na+ reabsorption in each portion of the nephron?
- PT: 67%
- DTL: 0%
- TAL: 25%
- DT: 4%
- CCD: 3%
How does aldosterone increase Na+ reabsorption?
Upregulates the activity of the Na+/K+ ATPase pump increasing the concentration gradient of Na+ and causing more Na+ to be diffused into cells
T/F: Aldosterone also increase H+ secretion?
True
How is aldosterone secretion regulated?
The renin-angiotensin system
How does the renin-angiotensin system work?
- The liver secretes angiotensinogen
- The kidneys then secrete renin which is the enzyme that converts angiotensinogen to angiotensin I
- ACE enzyme in the blood then converts angiotensin I to angiotensin II
- Angiotensin II acts on the adrenal cortex and causes the secretion of aldosterone
What is the rate-limiting step of the RAA system?
The secretion of renin by the kidneys
Is secretion of angiotensinogen by the liver regulated?
No, it is constantly secreted into the blood same with ACE
What other factors can stimulate aldosterone secretion by the adrenal cortex?
- Elevated plasma K+
- ACTH
What other factor can inhibit aldosterone secretion by the adrenal cortex?
ANP
Where in the kidney is renin made?
Renin is secreted by the juxtaglomerular cells that are innervated by sympathetic nerve fibers and surround the afferent arteriole
What three factors cause an increase in renin secretion?
- Increased acitivty of renal sympathetic nerve due to low plasma volume.
- Decreased arterial pressure causes less stretch of AA that juxtaglomerular cells are sitting on.
- Decreased GFR causes less flow to the macula densa which causes less NaCL delivery to the macula densa (sensed by cells of macula densa which send signal to juxtaglomerular cells)
Macula densa?
Portion of the loop of henle coming back to the glomerulus made up of tall epithelial cells that can sense NaCl
Does aldosterone stimulate H2O reabsorption directly in the CCD?
NO
What is ANP?
A peptide hormone secreted by cells in the cardiac atria
What does ANP do?
Acts on the DCT and CCD to inihibit sodium reabsorption and increases GFR
What stimulates ANP secretion?
Increased total body sodium(increased extracellular fluid/plasma volume) this increases atrial wall stretch which stimulates the secretion of ANP
How does blood pressure affect sodium excretion?
Increased blood pressure increases sodium excretion (pressure natriuresis)
What is osmolarity?
The total solute concentration of a solution (measure of water concentration)
What does a high solution osmolarity mean?
The higher the solution osmolarity, the lower the water concentration
Hypoosmotic?
Having a total solute concentration less than that of normal extracellular fluid (300 mOsm)
Isoosmotic?
Having a total solute concentration equal to that of normal extracellular fluid
Hyperosmotic?
Having a total solute concentration greater than that of normal extracellular fluid
Majority of water reabsorption occurs where and how much ?
Mainly occurs in the proximal tubule about 67%(2/3 of total water reabsorption)
Major hormonal control of water reabsorption occurs where?
In both cortical and medullary collecting ducts
What does water reabsorption depend on?
Sodium reabsorption only in the proximal tubule
Describe how water reabsoprtion occurs?
- Since Na+ concentration is high in the ISF, the osmolarity in the ISF is high
- Since Na+ is moving from the tubular lumen, the osmolarity in the lumen is low
- This concenctration gradient causes Na+ to diffuse via osmosis into the ISF to decrease the osmolarity
- Since the ISF is very small, everything in the interstitium dissolves and is moved into the peritubular capillary via bulk flow
Does osmosis occur transcellularly or paracellularly?
Osmosis can occur both ways
If it occurs transcellularly both membranes must have water channels in order to transport the H2O
How does the body maintain water balance?
- When the water intake is small, the kidney reabsorbs more water
- When the water intake is large, the kidney reabsorbs less water
Max vs Min urine output?
Max.: 25L per day
Min.: 0.4L per day
Where does water regulation occur?
In the medullary collecting duct
Max concentration of urine?
1400 mOsm/L
During what part of the nephron does urine concentration occur?
As tubular fluid flows through the medullary collecting ducts
Two factors that affect urinary concentration?
- Hyperosmolarity of the ISF
- Presence of vasopressin
How does the medullary interstitial fluid become hyperosmotic?
Countercurrent multiplier system
Countercurrent flow in the loop of Henle?
Tubular fluid flows down in the descending limb and flows up in the ascending limb(opposite directions = countercurrent)
How does the ascending limb affect reabsorption of NaCl and Water?
The ascending limb actively reabsorbs NaCl and is impermeable to water
Step 1 of the countercurrent multiplier?
- Isoosmotic fluid flows in via the PT
- In the ascending limb NaCl is reabsorbed which lowers the osmolarity of the fluid(becomes hypoosmotic)
- Fluid in the interstitium becomes hyperosmotic due to increased NaCl
Step 2 of the countercurrent multiplier?
- The descending thin limb does not reabsorb NaCl but it is permeable to water.
- This means that the isoosmotic fluid that enters the descending thin limb becomes hyperosmotic because fluid will flow into the hyperosmotic interstitium created by step 1
Does water from the descending thin limb dilute the interstitium(more hypo osmotic)?
No, since the water is being carried away via the peritbular capillaries
How does fluid change going down the descending thin limb versus going up the ascending thin limb?
- DTL: Permeable to water the fluid becomes hyperosmotic
- ATL: Absorption of NaCl, the fluid becomes hypoosmotic
Where is the highest osmolarity in the loop of Henle?
At the bottom of the descending limb
What determines the final osmolarity gradient in the loop of henle?
The flow/speed of the tubular fluid + the length of the loop of Henle
T/F: The interstitium always matches the same dips in the loop of Henle?
True
Vasa Recta?
The capillaries that are supplying blood and recieving things from the loop of Henle
-Has a similar shape as the loop of Henle
Role of the vasa recta?
Minimizes the excessive loss of solute from the interstitium
What else contributes to medullary hyperosmolartiy?
Urea
T/F: Permeability of the epithelium depends on the tubular segment?
True, the proximal tubule has high permeability to water
What does the permeability of the tubule depend on?
Permeability of the tubule depends on the presence of water channels(aquaporins) in the plasma membrane of the tubule
How is water permeablilty in the CCD and MCD regulated?
Regulated by vasopressin
What is vasopressin?
A peptide hormone also called antidiuretic hormone(ADH)
What produces vasopressin?
It is produced by a group of hypothalamic neurons and released from the posterior lobe of the pituitary gland
Two receptors of vasopressin?
Both receptors are G protein coupled receptors
1. V1 receptor is found in the smooth muscle
2. V2 receptor is found in the kidney in the collecting duct cells
What does vasopressin do?
Stimulates the insertion of aquaporins in the luminal membrane of the collecting duct cells, increasing the water permeability
Why does vasopressin not increase aquaporins in the basolateral membrane?
The basolateral membrane always contins some water channels but there are none in the luminal membrane
When vasopressin is present vs not?
Present: collectng ducts become permeable to water (water reabsorption occurs)
Not present: collecting ducts impermeable to water(water diuresis(urination))
What is diabetes insidious?
A disease caused by the malfunction of the vasopressin system
- Either vasopressin is not there or the system does not work which leads to water diuresis(patient always has to pee)
Cortical collecting ducts with vasopressin ?
- Permeable to water due to insertion of aquaporins
-Surrounded by an interstitium that is isoosmotic
Medullary collecting ducts with vasopressin?
-Surrounded by a very hyperosmotic interstitium because we are deep in the medulla
-Water is continuosly reabsorbed here
When is the urine osmolariy 1400 mOsm?
If the person is severely dehydrated and all the water has been reabsorbed
MCD and CCD without vasopressin?
Neither are permeable to water, so hyperosmolarity is acquired through the DCT will remain
Major regulator of water excretion?
Vasopressin
Two mechanism that regulate vasopressin secretion?
- Osmoreceptor control (most important/sensitive)
- Baroreceptor(less sensitive/important)
Osmoreceptor control of vassopressin during increased ingestion of water?
- Increased water causes a decrease in body fluid osmolarity
- This leads to decreased firing by hypothalamic osmoreceptors
- Which leads to decreased vasopressin secretion which leads to less plasma vasopressin concentration
- This leads to lower tubular permeability to H2O in the collecting ducts , lower water reabsorption and increased H2O excretion(diuresis)
Baroreceptor control of vasopresiin during decreased ingestion of water?
- Lower plasma volume leads to lower venous, atrial and arterial pressures
- Baroreceptors in those blood vessels increase vasopressin secretion increasing plasma vasopressin concentration
- Increased vasopressin leads to increased tubular permeability and increased H2O reabsoprtion and lower H2O excretion
Baroreceptors vs Osmoreceptors?
Baroreceptors: Kick in when the plasma volume changes by 5%
Osmoreceptors: Kick in when the plasma volume changes by 1%-2%
How do baroreceptors induce thirst?
- Lower plasma volume causes baroreceptors to send signals to the thirst centre
- Lower plasma volume causes baroreceptors to increase angiotensin II which also signals to thirst centre
How do osmoreceptors induce thirst?
- Increased plasma osmolarity is sensed by osmoreceptors and causes them to signal to the thirst centre
T/F: dry mouth and throat can signal to thirst centre?
True
How does metering of water intake by GIT decrease thirst?
You feel thirsty then once you drink you immediately stop feeling thirsty even before the GIT has time to absorb the water and decrease plasma osmolarity. GIT senses the water and shuts down thirst
Most important mechanism signalling thirst?
The osmoreceptors
How do osmoreceptors signalling thirst change as we age?
As we age the osmoreceptors become less sensisstive which is why many elderly people die during heat waves because they can’t tell they are thirsty
T/F: During severe sweating loss of water is greater than loss of Na?
True, plasma concentration of Na appears why because H2O loss was greater than Na+ loss.
This is why plasma concentration of Na is not a good marker for total sodium in the body
Most abundant intracellular ion?
Potassium
98% of potassium is found in the intracellular fluid
2% of potassium is found in the extracellular fluid
Is the potassium in the extracellular fluid and if so for what?
Yes, it is extremely important for the function of excitable tissues(nerve and muscle)
Why is K concentration so important for muscle and nerve tissues?
The intracellular and extracellular concentration of K helps maintain the resting membrane potential of these tissues
Hyperkalemia?
High concentration of K in the extracellular fluid
Greater than 5 mEq/L
Hypokalemia?
Low concentration of K in the extracellular fluid
Less than 3.5 mEq/L
What do hyper/hypokalemia do?
Both cause abnormal rhythms of the heart and abnormalities of skeletal muscle contraction
Effect of hyperkalemia on the ECG?
K = 4.0 is normal ECG
K = 6.0 T-wave starts peaking
K = 8.0 Bradycardia
K greater than 8 causes ventricular tachycardia, must use diefibrilators to restore proper cardiac rhythm
Where do we get the majority of our potassium?
In our diet in fruits, chocoate, potatoes, etc.
How is potassium balance maintained by the kidney?
10% of our potassium intake is excreted into sweat/feces (this cannot be regulated)
90% of our potassium intake is excreted into urine (this can be regulated)
Is potassium freely filtered at the glomerulus?
Yes
Is potassium reabsorbed in the nephron?
Yes, normally the tubules in the nephron reabsorb most of the filtered K so that very little is excreted in the urine
Can K be secreted?
Yes, it can be secreted at the cortical collecting ducts and some in the DCT
Changes in excretion are mainly due to this secretion
Reabsorption range of potassium ?
If you have barely any potassium in the diet the body can reabsorb up to 99%
If you have excess potassium in the diet the body can reabsorb as little as 15% of the potassium
How much potassium is normally reabsorbed in a physiological condition?
86%
potassium is reabsorbed more than urea but less than water and sodium
How is potassium secreted in the CCD/DCT?
The Na/K ATPase pumps potassium into the cell as it pumps Na into the ISF. Then a K channel on the luminal membrane allows the potassium to diffuse into the tubule lumen then it is excreted in the urine
-Secretion of K+ in the CCD is coupled with Na+ reabsorption
How does aldosterone affect potassium secretion?
Aldosterone results in the upregulation of the Na/K ATPase and the K channel which means more potassium is secreted into the tubule lumen
Two main mechanisms that regulate potassium secretion?
- Dietary intake of potassium
- Aldosterone
Describe how dietary intake of potassium regulates its secretion when you increase potassium intake?
- Increase potassium intake
- Plasma potassium concentration increases
- Plasma potassium has two effects
- stimulates aldosterone secretion at the adrenal cortex which increases plasma concentration of aldosterone
-Plasma potassium concentration is directly sensed by the CCD cells which increases K secretion by the CCD cells - Potassium excretion increases
Describe how aldosterone can regulate potassium secretion ?
- Plasma potassium increases
- This stimulates the adrenal cortex leading to the release of aldosterone and increase of aldosterone in the plasma
- Aldosterone then leads to increased sodium reabsorption and increased potassium secretion in the CCD
- Overall, leads to an increase in potassium secretion
Describe how angiotensin II can be activated and leads to potassium excretion?
- Lower plasma volume is sensed by baroreceptors and stimulates the RAA system
- Angiotensin II is then released which acts on the adrenal cortex leading to increased production of aldosterone
- Increased aldosterone then leads to Increased potassium secretion and finally excretion in the urine
Hyperaldosteronism?
Conditions in which the adrenal hormone aldosterone is released in excess
Most common cause of Hyperaldosteronism?
Adenoma(tumour) of the adrenal gland that makes it produce aldosterone spontaneously and release it into the circulation
What does the adenoma of the adrenal gland do?
Causes constant sodium reabsorption and potassium secretion in the CCD
Leads to increased fluid volume, hypertension, hypokalemia, renin is supressed, metabolic alkalosis (aldosterone stimulates H+ secretion)
Why is the hydrogen ion concentration so important for metabolic reactions?
Metabolic reactions are highly sensitive to the pH(hydrogen ion concentration)
Is hydrogen ion concentration tightly regulated?
Yes
Normal pH in the human body ?
7.4
Normal H+ ion concentration in the human body ?
40 nmol/L(very small)
How do the kidneys adjust acid-base?
By the bicarbonate concentration
Main reaction controlling acid-base in the body?
CO2 + H2O —-(carbonic anhydrase)—- H2CO3 —– HCO3- + H+
What happens when a bicarbonate ion is lost from the body ?
It is equal to the body gaining a hydrogen ion
What happens when the body gains a bicarbonate ion?
It is equal to the body loosing a hydrogen ion
Four sources of hydrogen ion gain?
- Generation of H+ ions from CO2(metabolism of CO2)
- Production of nonvolatile acids from metabolism of protein and other organic molecules
- Gain of hydrogen ions due to loss of bicarbonate in diarrhea or other nongastric GI fluids(pancreatic bile, bile juice(rich in HCO3-)
- Gain of hydrogen ions due to loss of bicarbonate in the urine (pathological)
Four source of hydrogen ion loss?
- Hyperventilation (loss of CO2)
- Loss of hydrogen ions in the urine
- Loss of hydrogen ions in vomit(gastric juice is rich in HCl)
- Utilization of H+ ions in the metabolism of various organic anions
What are examples of nonvolatile acids?
Phosphoric acid
Sulfuric acid
Lactic acid
Average net production of nonvolatile acids?
40-80 mmol of H+ per day
What is a buffer?
Any substance that can reversibly bind H+
Function of the buffer?
Helps to maintain the pH
Major extracellular buffer in humans?
CO2/HCO3- system
Major intracellular buffer in humans?
phosphates and proteins
How does HCO3- act as a buffer?
When the body has extra H+ it binds to HCO3- which sequesters it from the body maintaining the pH
Does buffering eliminate the hydrogen ions?
NO, just sequesters it
T/F: The bicarbonate ion needs to be replaced either by removing an H+ ion or by regeneration a bicarbonate ion
True
How is Hydrogen ion balanced controlled?
- By the respiratory system (by controlling CO2)
- By the kidneys(by controlling HCO3-)
Do we need both the respiratory and kidney systems to control hydrogen balance?
Yes, both systems work together to minimize the change of hydrogen ion concentration. Both are needed for proper regulation.
What is alkalosis?
When the body has a low H+ concentration and the kidneys excrete HCO3-
What is acidosis?
When the body has a high H+ concentration and the kidneys produce new HCO3- and add it to the plasma
Henderson-Hasselbalch equation?
Used to calculate the pH in any fluid from the concentration of HCO3- and CO2. When one of the concnetrations move the other must also move in the same direction to minimize pH changes
How to determine how much bicarbonate is excreted in the urine?
HCO3-(excretion) = HCO3-(filtered) + HCO3-(secreted) - HCO3- (reabsorbed)
When is HCO3- secreted?
Only in extreme cases of alkalosis
Where is most bicarbonate reabsorbed in the nephron?
In the proximal convoluted tubule
When do kidneys not reabsorb all of the bicarbonate?
Only in cases of alkalosis
How is bicarbonate reabsorbed?
- In the epithelial cells of the PCT H2O and CO2 are converted to HCO3- and H+ in the presence of carbonic anhydrase
- HCO3- is transported into the ISF due to a transport protein and it is eventually taken up by the peritubular capillary
- The H+ ion is pumped into the tubule lumen
- In the tubule lumen, H+ combines with a molecule of HCO3- and is then converted back to H2O and CO2 because there is carbonic anhydrase on the surface of the luminal membrane to reverse the rxn
- H2o is then excreted in urine and CO2 excreted via the lungs
T/F: For every HCO3- filtered at the glomerulus one is reabsorbed at the peritbular capillaries?
True
How much HCO3- is absorbed at each part of the nephron?
PCT: 80%
TAL: 15%
CCD: 5%
T/F: If you live a healthy life your urine will not contain any HCO3-?
True
Two mechanisms by which HCO3- is added to the plasma?
- By H+ secretion and excretion on nonbicarbonate buffers (such as phosphate)
- By glutamine metabolism with NH4+ excretion
How does mechanism one add HCO3- to the plasma?
- H2O and CO2 in the cell is converted to HCO3- and H+ in the presence of carbonic anhydrase
- H+ is secreted into the tubular lumen but since there is no more HCO3- in the lumen it instead binds to some sort of acid and gets excreted
- HCO3- is transported into the ISF and peritubular capillary via transport protein
When does mechanism one of HCO3- addition occur?
Only occurs after all the HCO3- has been reabsorbed and is no longer available in the lumen
The capacity of mechanism one to produce HCO3-?
The capactity to produce bicarbonate is fairly limited, it can barely produce enough bicarbonate to match the daily H+ production of 40-80mmol
Mechanism 2 to add HCO3- into the plasma?
- PCT cells have a lot of glutamine transporters that let glutamine enter the cells either from the lumen or ISF.
- GLutamine is then metabolized in the cell into ammonium and bicarbonate
- Bicarbonate is them reabsorbed into the peritbular capillaries
- NH4+ enters into the lumen via sodium antitransporter and it is then excreted in the urine
Where does mechanism 2 occur?
In the proximal tubule
When is mechanism 2 of HCO3- addition used and what is its capacity?
- Mechanism 2 is used when the body has a lot of H+ in the body
-This mechanism has an enormous capacity to produce new HCO3- ions and is used during severe acidosis
Alkalosis?
Low concentration of H+ (high pH)
Acidosis?
High concentration of H+(low pH)
Respiratory vs Metabolic alkalosis/acidosis?
Respiratory: results from altered respiration(CO2)
Metabolic: results from altered HCO3-
Response to acidosis?
- 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 they are bound to non-HCO3- buffers such as HPO42-
- Tubular glutamine metabolism and ammonium excretion are enhanced, which also contributres new HCO3- to the plasma.
Net result of the response to renal acidosis?
More new HCO3- than usual are added to the plasma, therby compensating for the acidosis. Urine is highly acidic
Lowest attainable pH in the urine?
4.4
Renal responses to alkalosis?
- Rate of H+ secretion is inadequate to reabsorb all the filtered HCO3-, so HCO3- is excreted in the urine.
- Little to no H+ secretion on non-HCO3- buffers
- Tubular glutamine metabolism and ammonium excretion are decreased, so little to no new HCO3- is generated
Net result of alkalosis response?
-Plasma HCO3- decreases
-Urine is highly alkaline
Highest pH the urine can have and when is it seen?
pH greater than 7.4
Seen in alkalosis
Describe H+, HCO3- and Pco2 during respiratory acidosis?
CO2 + H2O —- H2CO3 — HCO3- + H+
PCO2 increases in cases of respiratory acidosis this drives the mass reaction forward creating more H+ ions and more HCO3- ions to compensate
Describe H+, HCO3- and Pco2 during respiratory alkalosis?
Pco2 decreases in cases of respiratory alkalosis which shifts the mass reaction to the left resulting in a lower H+ concentration and HCO3- concentration
Describe H+, HCO3- and Pco2 during metabolic alkalosis?
Decreased H+ concentration causes a gain of HCO3- due to less buffering. The respiratory system tries to compensate by increasing CO2 and driving the production of H+ ions
Describe H+, HCO3- and Pco2 during metabolic acidosis?
Increased H+ concentration causes a loss of HCO3- due to more buffering. Resp tries to compensate by lowering CO2 and reducing H+ concentration
Based on Henderson-Hasselbach equation how do the concentrations of HCO3- and CO2 change?
When one increase the other also increases and same for decreasing. This is to maintain the pH
Clinical examples of respiratory acidosis?
Respiratory failure with CO2 retention
Clinical examples of respiratory alkalosis?
Hyperventilation (ex. High altitiude)
Clinical examples of metabolic acidosis?
Diarrhea(loss of HCO3-) or renal failure (accumulation of inorganic acids)
Clinical examples of metabolic alkalosis?
Vomitting(loss of H+ ions due to loss of gastric juice), Hyperaldosteronisms(incretion of H+ secretion in the DCT and CCD)
Function of diuretics?
Drugs that increase the colume of urine excreted
How do diuretics work?
Act on the tubules to inhibit the reabsoprtion of sodium, along with chloride and or bicarbonate
Results in increased excretion of these ions and increased excretion of water
Why is chloride and bicarbonate reabsorption blocked?
These are the anions that are usually reabsorbed along with Na+
Most common type of diuretics?
Loop diuretics
How do loop diuretics work?
They act on the thick ascending limb of the loop of Henle and inhibit the cotransport of sodium, chloride and potassium and the luminal membrane
Example of a loop diuretic?
Furosemide
How do potassium-sparing diuretics function?
Inhibit sodium reabsorption in the CCD, and also inhibit potassium secretion there. Plasma concentration does not decrease.
Either block the action of aldosterone or block the epithelial sodium channel in the CCD
Examples of potassium-sparing diuretics?
-Amiloride
-Spironolactone
When are diuretics used?
In renal retention of salt and water
Abnormal expansion of the ECF (edema)
Why does congestive heart failure require the use of diuretics?
Congestive heart failure results in a lower cardiac output which means the kidneys recieve less blood and start to react as if the body needs more salt and water, so the kidneys reabsorb more sodium and water which can go to the legs and lungs
Why does hypertension require diuretics?
Renal retention of salt and water contribute to high blood pressure in paritents with hypertension
6 common features of kidney disease?
1.Proteinuria(glomerular filtrate contains protein)
2. Accumulation of waste products in the blood (urea, creatinine, phosphate, sulfate)
3. High potassium concentration in the blood
4. Metabolic acidosis(HCO3- handling impaired)
5. Anemia(decreased EPO secretion)
6. Decreased activation of vitamin D leading to hypocalcemia
Does 50% kidney function lead to kidney failure?
No, since those who lack a kidney or who donate a kidney are fine
When does kidney function become a problem and when is it life threatening?
When the function is decreased to 30% you start needing treatment
When the function is reduced to 10% life cannot be sustained and these ppl need kidney replacement therapy
Three renal replacement therapies?
- Hemodialysis
- Peritoneal dialysis
- Kidney transplantation
How is hemodialysis done?
- Aterial blood is drawn from the patient and pumped into a dialyzer with anticoagulant
- In the dialyzer there are fibers made of exchangeable membranes where waste product is removed from the blood and things that are missing in the blood are added
- The blood then leaves the dialyzer and reenters the patient
- This process occurs for four hours
How does peritoneal dialysis work?
- The patients’s own abdominal cavity (peritoneum) is used as a dialysis membrane
- Fluid is injected into the cavity of the patient via a tube inseted through the abdominal wall
- While the fluid is in the abdominal cavity the waste products are removed and other things are added back to the fluid(this exchange occurs multiple times)
Peritoneal vs Hemodialysis?
Peritoneal can occur at home
Best form of renal therapy?
Kidney transplantation
Where do we get kidneys for transplantation?
- From recently deceased persons
- From a living related/unrelated donor
Problem with kidney transplantations?
-Shortage of organs
First kidney transplantation?
Occurred in twins (do not need immunosuppressants) since they are identical
