kidneys Flashcards
What is vascular resistance?
Defines or dictates how much pressure we have. Pressure drives flow.
What is vascular conductance?
This is the inverse of vascular resistance
How does the circulatory system decrease overall resistance?
The system is organized in parallel which can lower overall resistance in comparison to a system organized in series.
What is the difference in cross-sectional area between the aorta and the capillaries?
aorta: 2.5 cm^2
capillaries: 2500 cm^2
how is velocity of blood flow measured?
velocity: blood flow/ cross sectional area
This explains why blood flow is so much faster in the aorta than in the capillaries.
What are the main high resistance vessels in the body?
small arteries and arterioles
proximal to the arterioles or before the arterioles would you expect pressure to be high or low?
High
Distal to the arterioles or after the arterioles would you expect pressure to be high or low?
Low
Describe laminar flow…
The ideal means of blood flow. Forward and orderly. Would expect the centermost blood in the vessel to flow the fastest as the blood adjacent to the vessel walls experiences resistance from those walls.
Which organ system gets way more blood flow than it needs?
The kidneys. They get 22% of the blood flow.
How can we manipulate Ohm’s law to calculate blood flow?
Flow = change in pressure / vascular resistance
What cells make up the capillaries and how thick are they?
endothelial cells. They are one cell layer thick.
What is the diameter and cross-sectional area of the aorta?
diameter: 2.5 cm
cross-sectional area: 4.5 cm^2
What is the diameter and cross-sectional area of the vena cava?
diameter: 3 cm
cross-sectional area: 18 cm^2 (there are two of these)
What is the pressure of blood in the arterial end of a capillary? The venous end?
pressure in the arterial end: 30 mmHg
pressure in the venous end: 10 mmHg
What is the “delta P” in the capillary or the pressure difference that is driving blood flow from the arterial end to the venous end?
20 mmHg
What are the four starling forces in the capillaries?
- hydrostatic capillary pressure: 30 mmHg (arterial end) and 10 mmHg (venous end)
- hydrostatic interstitial pressure: -3 mmHg (due to lymphatic system)
- plasma oncotic pressure: 28 mmHg
- interstitial fluid colloid osmotic pressure: 8 mmHg
What drives venous blood flow and lymphatic flow?
skeletal muscle contractions help move these one-way valve systems. Stop moving and these systems stop flowing and fluid can build up
What is Kf?
The capillary permeability coefficient (takes into account the surface area and fluid permeability or how porous the capillary membrane is)
What are the three main proteins that make up the plasma oncotic pressure?
- albumin
- globulins
- fibrinogen
Which three capillary starling forces favor filtration?
- hydrostatic capillary pressure
- interstitial fluid hydrostatic pressure (-)
- Interstitial fluid colloid osmotic pressure
Which capillary starling force opposes filtration?
- plasma oncotic pressure
What is the net filtration pressure at the arteriole end of the capillary? What does this mean?
13 mmHg this favors filtration as it is a positive number
What is the net filtration pressure at the venule end of the capillary? What does this mean?
-7 mmHg this favors reabsorption as it is a negative number
13 mmHg filtered and -7 mmHg reabsorbed… where does the rest of the filtered fluid go?
the lymphatic system
what is the average capillary blood pressure say somewhere in the middle of the capillary?
17.3 mmHg
What is the filtration rate of ALL of the glomerular capillaries combined?
125 mL/min
If blood flow is too low to the kidneys what does the afferent arteriole do?
dilates or relaxes
If renal blood flow is too high, what does the afferent arteriole do?
constricts
Which segment of the blood vessels in the kidneys has the highest vascular resistance?
Efferent arteriole
If the efferent arterioles constrict what would happen to glomerular colloid osmotic pressure?
The colloids would be more concentrated, the oncotic pressure would be higher.
If the efferent arterioles relax what would happen to glomerular colloid osmotic pressure?
The colloids would be less concentrated, the oncotic pressure would be less.
What is a filtration fraction and what is normal?
How much fluid is filtered, how much plasma has made it through the kidney. ~19% is normal
How do you calculate filtration fraction?
GFR / renal plasma flow (RPF)
125/660
How do you calculate the renal plasma flow?
CO= 5L/min
Renal blood flow (22% of CO) = 1100 mL/min
HCT= 0.40
plasma volume= 1-HCT (0.6)
Renal plasma flow= (0.6)(1100)= 660mL/min
If we constrict the afferent arteriole, what happens to the pressure in the glomerular capillaries and what happens to our GFR?
pressure in the capillaries decreases and our GFR decreases
If we relax the afferent arteriole, what happens to the pressure in the glomerular capillaries and what happens to our GFR?
pressure in the capillaries increases and our GFR increases
What happens to renal blood flow if we constrict the afferent arteriole?
Decreased renal blood flow
What happens to renal blood flow if the afferent arteriole is dilated?
increased renal blood flow
If we relax the efferent arteriole, what happens to the pressure in the glomerular capillaries and what happens to our GFR?
pressure in the glomerular capillaries decreases and the GFR decreases
If we constrict the efferent arteriole, what happens to the pressure in the glomerular capillaries and what happens to our GFR?
pressure in the glomerular capillaries increases and the GFR increases
What happens to renal blood flow if the efferent arteriole is dilated?
increased renal blood flow (dilation anywhere in the capillary system in the kidneys would increase renal blood flow)
What happens to renal blood flow if the efferent arteriole is constricted?
decreased renal blood flow
What is an example of a compound that gets filtered and partially reabsorbed?
Na+. We eat way more Na+ than we need. So only some of it gets reabsorbed
What is an example of a compound that gets filtered a little but gets completely reabsorbed?
Glucose (in a non-diabetic) patient.
Give an example of a compound that gets filtered a little and the gets heavily secreted out of the blood?
PAH or Para amino hippuric acid.
What is PAH a good diagnostic for and why?
Renal blood flow. Removal of PAH is highly dependent on renal blood flow.
What is the innermost layer of the glomerular capillaries made up of?
endothelial cells these are very permeable due to fenestrations
Describe the layers of the glomerular capillaries from the deepest to the outermost layer…
endothelial cells
basement membrane (connective tissue)
epithelial cells/ podocytes
What is significant about the basement membrane?
It has lots of negative charge which can repel negatively charged proteins to keep them from being filtered through the fenestrations
What is significant about the epithelial cells and podocytes?
these provide structural support which is important as pressure is higher. The podocytes have foot processes that have slit pores
Which is more filterable: a negatively charged sugar, neutral sugar or a positively charged sugar?
Most filterable: cation
Then neutral charge
Least filterable: anion
The kidney is responsible for long term regulation of lots of processes… name a few examples
- BP regulation
- pH by producing bicarb and getting rid of excess H+
- RBC via erythropoietin
- electrolyte regulation
- Vitamin D activation
- Blood sugar regulation
- Some drug clearance
- Waste removal of nitrogenous compounds like urea
- Osmolarity regulator
Name the arteries in sequence from the renal artery to the peritubular capillaries
renal artery–> segmental arteries–> interlobar arteries–> arcuate arteries–> interlobular arteries–> afferent arteriole–> glomerular capillaries–> efferent arteriole–> peritubular capillaries
Name the vein in sequence from the peritubular capillaries to the renal vein
peritubular capillaries–> interlobular veins–> arcuate veins–> interlobar veins–> segmental veins–> renal veins
where do we do the bulk of our filtration?
glomerular capillaries
where do we do the bulk of our reabsorption?
peritubular capillaries
What percent of our nephrons are cortical? and what percent are deep medullary nephrons?
90-95% are cortical
5-10% are deep medullary
How many nephrons does each kidndey have at birth?
1 million nephrons per kidney (2 kidneys = 2 million total nephrons)
What is the major feature of the blood vessels associated with the deep medullary nephrons (vasa recta)? And what is significant about this feature?
They have two ascending blood vessels for every descending blood vessel. This slows down the blood flow velocity which maintains a normal amount of solutes in the renal interstitial space which helps with reabsorption.
What is a feature of the blood vessels associated with the cortical nephrons?
the peritubular capillaries and associated tubules of the cortical nephrons dip down into the outer medulla and are more tortuous.
What nerve controls our bladder and bowels?
pudendal nerve
What is the pneumonic to remember which spinal nerves control the pudendal nerve?
“S2,3,4 keeps stuff off the floor”
What is the major risk of removing the prostate gland?
damage to the pudendal nerve
Where is the macula densa located in the kidney? and what is it responsible for?
It’s located in the thick ascending loop of Henle. These are specialized pressure sensing cells.
Describe the renal tubular structure from the corpuscle to the collecting ducts…
corpuscle–> proximal convoluted tubule–> proximal straight tubule–> thin descending limb–> thin ascending limb–> thick ascending limb–> distal convoluted tubule–> collecting duct (cortical–>outer medullary–> inner medullary)
When the macula densa senses low BP how does it respond?
the macula densa are adjacent to juxtaglomerular cells, when the MD sense low BP they signal to the JM cells to release renin. Renin leads to an increase in angiotensin II levels which constricts the efferent arteriole–> increases pressure in glomerulus–> increases filtration–> restore blood flow
What is renal clearance?
volume of plasma cleared of a compound per unit of time
If the kidney reabsorbs lots of fluid but not the stuff being filtered what would we say about the renal clearance of that filtrate?
The renal clearance of that compound is pretty high (mL/min)
If the kidney reabsorbs ALL of the compound along with the fluid that’s reabsorbed what would we say about renal clearance about that compound?
The renal clearance of that compound is low
Which compound is the “gold standard” to finding GFR?
inulin
What is usually used to estimate GFR?
creatinine
why do we usually use creatinine clearance to measure GFR?
it’s easier, inulin is exogenous, in order to measure a true GFR, need to inject inulin into the body.
what compound do we use to estimate renal blood flow?
PAH “para amino hippuric acid”
Which compound is considered heavily secreted? How much is cleared by the kidneys?
PAH. 90% gets excreted.
Which compound is considered completely filtered?
Inulin
An increase in blood pressure overtime can reek havoc on our glomerular capillaries how?
increased BP can lead to stiffened and calcified arterioles. Podocytes are disrupted in the epithelium and fenestrations in the endothelium are widened.
Where specifically does angiotensin II act?
It constricts both the afferent and efferent arteriole but has a net effect on efferent arteriole constriction. Increases glomerular pressure and GFR.
Where specifically do drugs “in our medicine cabinets” primarily act on the kidneys?
These constrict the afferent arteriole more than the efferent arteriole. Decreasing GFR.
Where specifically do pressors and vasodilators work?
on both the afferent and efferent arterioles.
What would happen at the macula densa if BP was high?
Increased NaCl sensed by MD cells –> decrease Ang II –> dilate efferent arteriole
What would happen at the macula dense if BP was low?
filtration deficiency –> MD cells see less NaCl –> increase Ang II –> constrict efferent arteriole
How does the macula densa sense the filtration rate of the
by counting Na+ and Cl+ ions (a # not a concentration)
If GFR is low, what happens at the MD cells?
filter less Na+ and Cl- and have a normal amount of Na+/Cl- reabsorption. This would result in a net lower Na+ and Cl- that reach MD cells. They see this and respond by increasing Ang II, constrict efferent arteriole, increase GFR.
How does angiotensin II cause an increase in BP?
Increases the amount of Na+ reabsorbed by the proximal tubule reabsorbed increasing water retention in the blood increasing BP.
Say you have an increased amount of Na+ reabsorbed at the proximal tubule, but GFR is normal what would happen at MD cells?
MD cells would think GFR is low as there is less Na+ and Cl- reaching the counters. This would increase Ang II and increase BP, causing the kidney to have a higher than normal GFR
What is an example of what could increase Na+ reabsorption at the proximal tubule?
High glucose and high amino acids (coupled with Na+ transportation).
How does uncontrolled diabetes lead to kidney problems?
Increased glucose leads to increased Na+ reabsorption at the PCT. There is less Na+ that reaches MD. The MD interpret this as a low GFR and take steps to increase GFR by releasing more ang II. (Hyperfiltration initiated by high blood sugar)
Why can giving an ACE inhibitor or ARB help with hyperfiltration caused by diabetes?
ACEi and ARB’s decrease amount of circulating Ang II from uncontrolled diabetes induced hyperfiltration
The side of the tubular cells in the proximal convoluted tubule on the side adjacent to the tubular lumen is called what?
Apical side
The side of the tubular cells in the proximal convoluted tubule on the side adjacent to the interstitial fluid is called what?
basolateral side
Where in the PCT is most of our glucose absorbed? By what transporters?
In the first segment of the PCT (S1 segment) 90% is absorbed by the SGLT2 transporters on the apical side and transported to the interstitium via GLUT2 transporters on the basolateral side.
What is the exchange rate of the SGLT2 pumps and what is their affinity for glucose?
1 glucose for 1 Na+ (more efficient). Lower affinity.
What is the exchange rate of the SGLT1 pumps and what is their affinity for glucose?
1 glucose for 2 Na+. Higher affinity.
Where is the rest of our glucose absorbed in the PCT?
The remaining 10% is reabsorbed by the S2 and S3 segments of the PCT via SGLT1 transporters on the apical side and GLUT1 on the basolateral side.
When does blood glucose start showing glucose in the urine?
At “threshold” somewhere a little less than 200 mg/dL
At what blood glucose are our glucose transporters saturated?
At “transport maximum” somewhere are 300 mg/dL
At what blood glucose will ALL of our extra glucose get excreted?
at about 300 mg/dL (when transporters are completely saturated)
Where is the MD located?
at the very end of the thick ascending loop of Henle
Which cells release renin?
juxtaglomerular cells?
What is the rate limiting step of angiotensin II formation?
renin
What is the primary effect afferent arteriole dilation has on the kidneys?
increased renal blood flow. Increasing GFR.
What is the primary effect efferent arteriole dilation has on the kidneys?
increased glomerular hydrostatic pressure increasing GFR.
What would speed up the Na+/K+ ATPase pump in the PCT?
Ang II
What are the three pumps angiotensin II effects at the PCT?
Speed up Na/K pumps
Speed up Na/H counter-transport pumps
Speed up Na/Bicarb co-transport pumps
How does Cl- get reabsorbed?
Na+ and water get reabsorbed transcellularly
Cl- follows Na+ and gets reabsorbed via the paracellular route
What is another name for the net reabsorption pressure of 10 mmHg at the peritubular capillaries?
Bulk flow
What compound is found in large quantities in the renal interstitial space to aid osmosis?
urea
Where is the brush border and what does it do?
Its on the luminal side of the PCT cells. This increases SA 20fold. Allows for more transporters for reabsorption.
What is the average membrane potential in the kidneys?
-70mV
How does the body reabsorb protein that gets filtered?
via endocytosis or pinocytosis. The proteins get broken down to their amino acids and reabsorbed via endocytosis to the int. space and back into the peritubular capillaries
How much protein do we filter at the glomerulus? How much gets reabsorbed and how much ultimately gets excreted in the urine?
1.8 grams of protein gets filtered. 1.7 grams gets reabsorbed and 100 mg shows up in the urine.
What is the primary site of Na+ reabsorption in the PCT?
NHE (the Na+/H+ exchanger)
What would happen if we gave someone a carbonic anhydrase inhibitor?
Bicarb wasting which would lead to acidosis.
List three important functions of the proximal tubule?
Na+/Cl- and H20 reabsorption
glucose and amino acid reabsorption
Acid/base balance
How is bicarb produced?
from glutamine (produced by the liver) and converted by proximal tubule cells to bicarb (HCO3-) and ammonium (NH4+)
Why do people with liver failure have a difficult time with pH management?
can’t make as much glutamine in the liver
Name the important urinary buffers?
Phosphate
Ammonium
Bicarb
How does the parathyroid gland control the Ca2+ levels in the blood.
The parathyroid gland monitors extracellular Ca2+. If it’s low it increases PTH which encourages vit. D activation which picks up dietary Ca2+. Also increases the amount of Ca2+ reabsorbed by increasing Ca2+ channels in the PCT and Distal tubule. PTH also stimulates bone breakdown to free up more Ca2+
What do osteoclasts do?
Break down bone (Ca2+ storage place)
What do osteoblasts do?
Build new bone
What are some endogenous organic cations that are secreted in the PCT ?
ACh
Creatinine
DA
Epi
Histamine
5-HT
NE
What are some exogenous organic cations that are secreted in the PCT?
Atropine
Isoproterenol
Morphine
Procaine
Quinine
TEA
What type of antiporter/s do cations use when secreted in the PCT?
H+/cation counter-transport
What type of antiporter/s do anions use to get secreted into the PCT?
alpha ketoglutarate/ Na+ cotransport and then aKG/Anion counter-transport
What are some organic endogenous anions that get secreted into the PCT?
Bile salts
Hippurates
Oxalate
PG’s
FA’s
What are some exogenous organic anions that are secreted in the PCT?
Furosemide
Penicillin
Salicylates
How were the antiporter secretory processes for cations and anions discovered?
During WW2 someone noticed blood levels of penicillin would drop (kidneys excreted it too quickly) and if they gave the patient a synthetic hippurate with the penicillin it would stay in the bloodstream longer as the hippurates competitively inhibit the antiporters responsible for secreting the penicillin.
How much water/ions/compounds are reabsorbed in the PCT?
2/3 of everything that was filtered at the glomerulus
What is happening at the thin descending loop of Henle?
Water reabsorption (secondary place where water is reabsorbed second to the PCT)
What is happening at the thin ascending loop of Henle?
Some NaCl reabsorption via Na+/Cl- transporter that is driven by ATP
What is happening at the thick ascending loop of Henle?
Minimal water reabsorption. Lots of reabsorption of Mg++,Ca++, Na+, K+.
What role does the thick ascending loop of Henle have on the renal interstitium?
It contributes to the concentration of the renal interstitium.
How are lizards able to live in the desert and on minimal water?
They have a much more concentrated renal interstitium and are able to reabsorb more water out the tubule to survive.
Where are the principle cells?
The end of the distal tubule and all along the collecting duct
What do the principle cells do?
These control how much of the leftover solutes will get reabsorbed or excreted.
What controls water reabsorption at the collecting ducts?
ADH
How much of our electrolytes are reabsorbed in the thick ascending loop of Henle?
25% of the ions
Where are aldosterone receptors found?
principle cells
What does aldosterone do?
Speeds up Na+/K+ pump. Causes increased K+ inside the cell and loss of Na+ into the tubule. The K+ can get reabsorbed.
What are the two types of K+ channels in the principle cells?
ROMK: sequestered until needed. When we need more K+ excretion these will be put into the cell wall
BK: secondary K+ channels that open (normally closed) if we need to increase K+ excretion a lot
How do Thiazides work?
They block Na/Cl pumps at the distal tubule
How does parathyroid hormone work (PTH)?
It increases Ca2+ absorption at the distal tubule
What does spironolactone do?
inhibits aldosterone receptors in the principle cells at the distal tubule. This slows down the Na/K pumps (leading to more K+ reabsorption)
What does triamterene and amiloride do?
Blocks ENaC channels. This blocks Na+ from going into principle cells in the distal tubule and indirectly inhibits K+ from leaving the principle cells via its channel.
What are the three zones from outermost to innermost of the adrenal gland?
zona glomerulosa–> zona fasciculata –> zona reticularis–> medulla
What gets made in the zona glomerulosa?
aldosterone
What gets made in the zona fasciculata and reticularis?
cortisol, androstenedione and estrogens
What gets made in the adrenal medulla? What’s the ratio?
Epi and NE (4:1)
What increases aldosterone release from the zona glomerulosa?
increased K+ and increased
Angiotensin II
name a glucocorticoid
cortisol
How does cortisol increase BP?
It looks like aldosterone and excess cortisol can bind aldo-R stimulating reabsorption of NaCl and water raising BP
name a mineralocorticoid
aldosterone
What enzyme keeps increased cortisol in check?
11beta HSD type 2 enzyme
What does licorice do to BP?
Too much licorice (like in smokeless tobacco) can inhibit 11beta HSD enzymes which can lead to increased BP and hypokalemia.
What is special about intercalated cells at the distal tubule?
they are good for acid/base balance. Can get rid of acid and bases.
What are the two types of intercalated cells?
Type A: secrete H+ (get rid of acid)
Type B: reabsorb H+, secrete HCO3- (get rid of bases)
What two pumps do the Type A intercalated cells use to secrete H+ in the late distal tubule and collecting ducts?
H+/K+ ATPase pumps
and H+ ATPase pumps
Where are principle and intercalated cells found?
in the late portion of the distal tubule and the collecting duct.
What are the primary roles of intercalated cells and principle cells?
Principle cells: K+ management
Intercalated cells: acid/base issues
Both: H20 balance
Both are sensitive to ADH
Where are V2 receptors and what binds them?
In the late distal tubule and collecting duct. ADH binds them.
When ADH binds the V2 receptors what happens?
This generates cAMP, resulting in activated PKA which phosphorylates aquaporin vesicles. This mobilizes them to the cell wall to allow water into the cell.
Nephrogenic diabetes insipidus
If there is problem with the kidney and how it responds to vasopressin.
Give an example of something that could cause nephrogenic DI?
Excessive amounts of Lithium
Central diabetes insipidus
A problem with the release of ADH/vasopressin.
Give an example of something that could cause central DI?
Head injury or pituitary tumor
What is considered the “diluting segment” of the nephron?
the distal tubule and collecting ducts. If we don’t reabsorb any water at this point this can make the urine more and more dilute (as low as 50 mOsm).
What does alcohol do to ADH?
Decreases the amount of ADH released from the brain and impairs the kidney’s response to ADH
Where is ADH produced?
The supraoptic nuclei produces 5/6 and the paraventricular nuclei produces 1/6 of the ADH.
Where does the ADH go after it is produced?
The nuclei deliver the ADH to posterior pituitary gland. There is a fairly rich blood supply here that can deliver the ADH to the kidneys.
What is another name for the posterior pituitary gland?
neurohypophysis
What is another name for the anterior pituitary gland?
adenohypophysis
If the osmoreceptors experience increased Na+ in the ECF (blood) what happens to ADH?
Water leaves the cell, the osmoreceptor shrinks. This increases the action potential firing to the pituitary gland this increases the amount of ADH that is released.
If the osmoreceptors experience decreases in Na+ in the extracellular fluid (blood) what happens to ADH?
Swelling osmoreceptors slows the rate of action potentials to the pituitary gland and decreases the amount of ADH released.
If we have lots of ADH around, what will the concentration of the urine look like?
It’ll be very concentrated. (the blood will be diluted)
If we have very little ADH around, what will the concentration of the urine look like?
It’ll be very dilute.
Where does ADH have the largest role in variation of urine osmolarity?
The collecting duct (due to ADH) and the loop of Henle (due to urea)
If we are in a state of antidiuresis what types of things might we see in the basolateral side of the collecting duct?
urea transporters and aquaporins. The urea helps draw the water through the aquaporins via osmosis.
What is the only thing that can affect water reabsorption without affecting electrolyte reabsorption?
ADH
ADH is the primary controller of _________ osmolarity
plasma
What are some things that decrease thirst?
reduction in osmolarity
increase in blood volume
if BP is high
less Ang II
full stomach
What are some things that can increase thirst?
Increased plasma osmolarity
decrease in blood volume
low BP
high Ang II
dry mouth and lips
What are some things that would decrease ADH?
reduced plasma osmolarity
High BP or blood volume
alcohol
clonidine
Haldol
What are some things that would increase ADH
increased plasma osmolarity
low BP or blood volume
nausea/vomiting
morphine
nicotine
In the ideal world under ideal conditions, what is a normal urine osmolarity?
600 mOsm/L
What is the “normal” Na+ concentration in the urine?
600mmol/L
What would cause an increased urine osmolarity of 1200 mOsm/L and elevated plasma Na+?
Dehydration
When given diuretics where does the majority of the fluids come from?
extracellular fluids (4/5) from the interstitial fluid (1/5) from the plasma
How does salt act as a flavor enhancer?
Taste buds have Na+ channels. When you add Na+ to food it excites these cells making them more sensitive to other flavors.
If we take in too much salt, how do we get rid of the excess NaCl?
Increased Na+ intake, Increased Na+ concentration in the blood–> more Na+ to the MD cells, these decrease Ang II release and decrease aldosterone
How does sodium effect blood pressure?
Increased Na+ increases water reabsorption and blood volume–> increased BP
What is essential hypertension?
A higher baseline BP/MAP but less influenced by Na+ and H2O intake
What is Salt-sensitive or renovascular hypertension?
This form of HTN is directly dependent on NaCl intake (prevalent in African American population)
If you get rid of half of your nephrons, what happens to blood creatinine?
Creatinine in the blood doubles to be able to clear as much as it did before.
Creatinine excretion rate = _______________
Creatinine production rate
What happens to the glomerular blood pressure with a unilateral nephrectomy?
The pressure stays the same
When you remove one kidney, how do the remaining nephrons (1 million instead of 2) “pick up the slack”
The remaining nephrons are able to maintain an excretion rate of 1mL/min by decreasing the amount of Na+ and water reabsorbed by the tubules. This maintains a fluid balance but compromises filtration.
What is the main mechanism that hastens damage of the remaining nephrons with kidney disease?
The volume excreted per nephron to maintain an excretion rate of 1mL/min is much higher (due to the loss of nephrons) which causes damage and further loss of nephrons
What can you do to decrease the workload on the remaining nephrons if you are in kidney failure?
Decrease Na+ and K+ intake. Manage diabetes. Don’t take in too much protein.
If you give someone a liter of isotonic saline which fluid compartments will effect?
It will stay in the ECF and the majority will end up in the interstitial fluid (4/5) and (1/5) will remain in the plasma.
If you give someone 0.45 % NS, what happens to the overall osmolarity and where will the fluid end up?
This will lower overall osmolarity. Both ICF and ECF will increase (since you are adding more water than NaCl some of the water will go into the cells).
If you give say 3% saline, what happens to the overall osmolarity and where will the fluids end up?
It will increase overall osmolarity. The increased NaCl will draw water out of the cells into the ECF, so ICF will decrease and ECF will increase.
In the event of a hemorrhage, which cells respond to help mitigate loss of pressure/blood flow?
The juxtaglomerular cells in the kidneys are influenced by sympathetic outflow. If there is a decrease in MAP they will secrete more renin to increase Ang II and increase BP
Autoregulation serves to maintain near constancy (less minute by minute variation) of what?
Glomerular hydrostatic pressure, GFR, filtration of solutes and water and renal blood flow.
What is responsible for autoregulation?
- contraction or relaxation of arterioles
- tubuloglomerular feedback
- sympathetic regulation from the renal nerve
How much of the body mass is water?
60%
How much of the total body water is in ICF? ECF?
ICF: 2/3
ECF: 1/3
In the ECF, how much of the water is plasma? How much is interstitial fluid?
Plasma:1/5
ISF: 4/5
With diabetes insipidus, where would you expect the urine to be most dilute in the tubule?
In the collecting ducts, as there is a problem with not enough ADH or a lack of response to ADH
If you decrease GFR by 50% what would you expect to see with creatine excretion rate, creatinine clearance, and serum creatinine in 6 weeks?
decreased creatinine excretion rate initially. Over time the kidneys adjust and there would be no change in creatinine excretion rate, decreased creatinine clearance and increased serum creatinine levels.
Increased extracellular osmolarity would cause hyperkalemia or hypokalemia.
Increased ECF osmolarity would cause the cell to shrink. This concentrates K+ on the inside of the cell, increasing its driving force to leave the cell leading to hyperkalemia
Acute metabolic alkalosis_______ K+ secretion in the DCT and C.D’s and ________ plasma K+ concentration.
increases, decreases
Name four things that can increase K+ uptake into the cells…
- Aldosterone
- Epinephrine (increased beta-adrenergic activity)
- Insulin
- Metabolic alkalosis
Name six things that shift K+ out of the cell (increase ECF K+ concentration)…
- Aldosterone deficiency (Addison’s disease)
- Insulin deficiency (DM)
- Metabolic acidosis
- Excessive exercise
- Increased plasma osmolarity
- Beta blockade
What causes patients with deficient levels of aldosterone to have hyperkalemia? (example Addison’s disease)
Aldosterone secretion is stimulated by increased levels of K+ in the blood. This causes an increase of K+ secretion causing hyperkalemia
What causes patients with excess aldosterone secretion to have hypokalemia? (ex. Conn syndrome)
increased K+ in the blood (after a meal) stimulates aldosterone, if the patient has excessive aldosterone production this will increase the uptake of K+ into the cells leading to hypokalemia
How does insulin decrease plasma concentration of K+?
Insulin speeds up the Na+/K+ ATPase pumps causing more K+ to be pumped into the cell.
Why is someone with Type II DM more likely to be hyperkalemic?
If their cells are not responding to insulin, Na+/K+ ATPase pumps are not as efficient after ingesting a large meal. Therefore more of the K+ will remain in the blood and less will be pumped into the cell
How does metabolic acidosis lead to hyperkalemia (two mechanisms)?
Primary mechanism: more H+ get into the cell and push K+ out of the cell via K+ leak channels
Secondary mechanism: acidosis decreases Na+/K+ ATPase pump activity. This decreases K+ uptake into the cells, there is also a decrease in K+ secretion into the tubule as well leading to hyperkalemia.
How does metabolic alkalosis lead to hypokalemia?
Alkalosis also speeds up Na+/K+ ATPase activity. This increases K+ uptake into the cells and increases K+ secretion into the tubule which causes hypokalemia.
What could lower the filtration coefficient (Kf)?
Contraction of the podocytes (in response to changes in renal arterial pressure) would restrict flow through the capillaries reducing Kf and subsequently the GFR.
What percent of predicted GFR constitutes renal insufficiency? Chronic renal failure? End stage renal disease?
Renal insufficiency: 50-20% GFR
Chronic renal failure: 20-5% GFR
ESRD: <5% GFR
What is a compound in volatile anesthetics that is damaging to the kidneys?
fluorine
What is the mortality rate associated with acute renal failure?
90%
What percent of patients develop acute kidney injury with anesthesia?
7%
What are some things we could use to get rid of K+ in the case of hyperkalemia?
- Diuretics like a loop diuretic
- Insulin (tuck it into the cells)
- Give a beta agonist (tucks K+ inside the cell)
How does insulin increase K+ reabsorption into the cell?
Insulin receptors drive GLUT 4 into the cell wall and increase Na+/K+ ATPase pumps.
How do beta agonists increase K+ uptake into the cells?
Increases Na+/K+ ATPase pump activity.
Why does someone who is on a beta blocker have to be careful when considering exercising? (~35minutes into lecture)
Both excessive exercise and beta blockade can increase the amount of K+ that leaks out of the cell causing hyperkalemia.
Where do protons come from?
From inside the cell, as a byproduct of metabolism
What is the same or similar from the plasma in the glomerular capillaries to the end of the PCT?
Osmolarity should be about the same because the PCT is very leaky to water
If the TAL of the loop of Henle were to stop reabsorbing Na+, the final urine would be?
Iso-osmotic with the plasma, and dependent on ADH.
If you consume a meal high in NaCl and drink no water, what happens?
The increase in plasma Na+ is sensed by osmoreceptors in the hypothalamus, which stimulates ADH production and ultimately increased water reabsorption in the distal nephron.
If you are a healthy 30 something and consume a meal high in potassium will you become hyperkalemic?
No, the increase in K+ is dealt with in multiple ways. First, insulin triggered by eating a meal will pack K+ away into the cells. Leftover K+ is secreted at the distal nephron via ROMK and BK channels and excreted.
