Renal Physiology Flashcards
The kidney makes: ______________________, _______________________, such as _____________________ and ____________________ in the active form
Renin
Hormones
Erythropoietin
Vit D
Once urine is formed and exiting the medulla, it enters the ___________ calyx then the ___________ calyx and further into the renal ______________ and finally to the ureter
minor
major
pelvis
As the interlobar artery flows up the renal pyramid, it then runs parallel across the medulla and cortex where the artery is now termed , _________________ artery. These artery then run perpendicular up into the medulla and are now termed: _________________ artery. The _____________ arteriole branch off of the interlobar artery
Arcuate artery
Interlobar artery
afferent
The ______________ comprise 90% of the total glomeruli of the kidney and are located in the outer 2/3 of the cortex. The remaining 10% are termed: _____________
Cortical glomeruli
Juxtamedullary glomeruli
The peritubular capillaries are found:
They surround the _________________ and ___________________ ________________
Entirely in the cortex
Proximal and distal tubules
What are some differences of the juxtamedullary glomeruli?
1.) Deep within the cortex, proximal to the medulla
2.) The efferent arteriole from the glomeruli form the vasa recta that are vital to concentrating urine
3.) The vasa recta stretch deep into the medulla
The glomerular capillary is surrounded by:
Bowman’s capsule
Bowman’s capsule is formed by epithelial cells which then stretches on to form the:
Proximal tubule
The glomerulus has capillary ___________. When filtration occurs, the ______________ and ________________ ________________ of the plasma are forced across the capillary wall known as filtration.
loops
water
small solutes
T/F: The glomerulus itself cannot contract since it is comprised of capillary loops
False, in the central core of the glomerulus there is mesangial cell that can contract
List some functions of the mesangial cell
Contractile
Synthesizes products
Role in phagocytosis and immunity
In the glomerular capillary loop, there is a layer of endothelial cells. These cells like on a basement membrane that is proximal to Bowman’s capsule. Outside of the basement membrane exists the huge cell type:
Podocyte
What do podocytes do?
Within Bowman’s capsule inside the glomerular filtrate that give rise to “footlike projections” that surround the basement membrane of glomerular capillary.
What does fenestrated mean?
With perforations
What is the basement membrane within the glomerulus made of?
Gel layer that is supported by a matrix
T/F: Only the juxtamedullary glomeruli have a loop of Henle extending into the medulla
False, both have a loop of Henle extending into the medulla. The JMG extends much deeper into the medulla
What is the macula densa?
The portion of the thick ascending loop of Henle that is making contact with the afferent arteriole of the glomerulus
Where do you find the peritubular capillaries? Where do you find the vasa recta capillary network?
1.) surrounding the tubules of the superficial glomeruli
2.) Vasa recta ascending and descending run parallel to the loop of Henle of the juxtamedullary glomeruli
What is the Juxtaglomerular apparatus comprised of?
Macula densa + extraglomerular mesangium + terminal portion of the afferent arteriole
The thick ascending loop of Henle contacts with the afferent arteriole. What specialized cell type are going to communicate with the terminal portion of the afferent arteriole?
Cells termed macula densa communicate with extraglomerular mesangial cells
What two things are being communicated between the macula densa and mesangial cells at the Juxtaglomerular apparatus?
1.) Communicate to influence vascular tone if the afferent arteriole
2.) Communicate to influence granular cells that are at the top of the glomerulus underneath the afferent arteriole
Where are granular cells? What do they do? What is their structure type?
1.) Cells near the top portion of the glomerulus
2.) They synthesize renin and release
3.) specialized smooth muscle
What is the term for the side of epithelial cells that faces the tubule lumen?
Luminal or apical surface
What connects the epithelial cells lining the nephron tubules?
Tight junctions
What is the term for the epithelial cells that are facing the interstitial fluid of the nephron?
Peritubular or basolateral
Where are the Na+/K+ ATPase transporters found in the epithelial cells of the tubule
On the peritubular/basolateral side only so that sodium can only be reabsorbed back into the body
Why is the proximal tubule have a brush border?
Active site of reabsorption
Name the two types of cells found in the cortical collecting duct
1.) Principal cell
2.) Intercalated cell
T/F: Like most organ systems, the parasympathetic and sympathetic play a significant innervation role in the renal system
False, controlled by sympathetic. NO significant parasympathetic innervation
Glomerular filtration rate is normally very high. The normal is approx:
80-200 ml per minute
What are the 6 requirements of a substance to be used to measure GFR
1.) Freely filtered at the glomerulus so it will reach the tubule
2.) Not reabsorbed in the tubule
3.) Not secreted in the tubule
4.) Not metabolized
5.) Not toxic
6.) Not effect on the kidney
When determining if a substance is appropriate to use for GFR calculation, the amount filtered must be equal to the:
Amount excreted in the urine
(If freely filtered) Rate of filtration of substance X =
Plasma concentration x (Px) * GFR
Rate of excretion of substance X =
Urine concentration of X * urine flow rate (v)
Why is inulin used to measure GFR?
Because it cannot cross the cell wall of the tubule
If you have concentration of urine and plasma, what is the equation to calculate GFR?
GFR = ( [Ux]/[Px] ) * v
where Ux is urine concentration of substance X
Px is plasma concentration of substance X
v is urine flow rate
What is an endogenous substance that can be used to measure GFR? What is the drawback to this substtance?
Creatinine is freely filtered and not reabsorbed made in skeletal muscle
Drawback: there is some tubule secretion downstream from glomerulus so there is a little bit more creatinine cleared than is filtered at the glomerulus
What endogenous substance is typically used to measure GFR?
Creatinine
Creatine production matches creatinine excretion. Therefore, if GFR halves, what happens to plasma concentration Creatinine?
Its plasma concentration doubles
The higher the plasma creatinine, the:
lower the GFR
Why must creatinine measurement be adjusted when calculating GFR?
It can be affected in the setting of pregnancy, muscle wasting disease, and aging
What are three additional factors to consider when calculating eGFR from creatinine clearance?
Age, body weight in Kg, and sex
What is the clearance equation?
Cx = ( [Ux] / [Px] ) * V
C clearance substance X
U concentration of substance X
Plasma concentration of substance X
urine flow
Define clearance of a substance
A volume of plasma from which all of the substance is removed per unit time
T/F: Urinary clearance is the same as renal clearance
True
What is the equation for final urinary excretion of a substance?
[Ux] V = filtered x - reabsorbed x + secreted x
What is fractional clearance?
Method used to evaluate how the kidney handles a particular substance compared to how the substance is filtered
Compare the clearance to inulin, such that if clearance is the same of substance X compared to inulin, then it is considered freely filtered
If clearance substance X is < clearance inulin, what does this tell you?
There is reabsorption
Is clearance of substance X greater than or less than inulin clearance when there is secretion of substance X
Clearance substance X is greater than clearance inulin = substance X secretion
_______________ and _________________ are two examples of substances that are entirely (or almost entirely) reabsorbed and filtered by the kidney
Glucose (entirely reabsorbed normally)
Phosphate (mostly reabsorbed)
What is the normal plasma glucose?
100 mg/dL
What happens when the filtered load of the glomerulus is overloaded?
The substance is excreted through the urine
What is the expected fractional clearance of glucose? How would it compare to the fractional clearance of inluin?
Fractional clearance glucose is 0.0
Is lower to inulin because all of the glucose is reabsorbed rather than entirely excreted
What is the fractional clearance of phosphate?
0.2
Where is phosphate absorbed? What is its absorption coupled to?
Absorbed at the proximal tubule and coupled to sodium absorption
Why is fractional clearance of phosphate greater than factional clearance of glucose?
Because the reabsorptive capacity of phosphate is lower in the proximal tubule
What does phosphate’s fractional clearance of 0.2 actually mean?
20% of the filtered phosphate is excreted while the remaining 80% is absorbed
What is the fractional clearance of water?
0.01
What is the approx. amount of water being filtered at the glomerulus per minute?
~120 mL/min
Water reabsorption is ___________________ along the nephron
Passively
How does the changing concentration of inulin in the kidney relate to water reabsorption?
The plasma concentration of inulin is going to be less than what is excreted. This is because as inulin travels down the tubule, water is being reabsorbed which makes the concentration of inulin greater
Urine to plasma concentration (U/Pin) ratio of:
1 means:
U/Pin ratio of 1 means there is equal plasma concentration of inulin compared to urine [inulin]. If there was water absorption then the urine concentration would be high. Thus NO water reabsorption
Urine to plasma concentration (U/Pin) ratio of:
2 means:
Why?
U/P in ratio of 2 means the urine [inulin] is greater than plasma [inulin], thus some water is reabsorbed since the urine concentration is higher as the inulin traveled down the tubule. More specifically, 50% of water is reabsorbed
Urine to plasma concentration (U/Pin) ratio of:
100 means:
Why?
U/ Pin ratio of 100 means almost all of the water is reabsorbed since the urine [inulin] is much much greater than the plasma [inulin]
In normal humans, 99% of water is reabsorbed and 1% is excreted
Define free water of the body
Solute free, pure (distilled) water
What is free water clearance?
Comparing the volume of free water leaving the body compared to solute
What is the question to calculate free water clearance?
Clearance H20 = V - C osm
V is urine flow rate (Total amount of water leaving body)
C osm is osmolar clearance
C osm = U [osmolar] / P [osmolar] * V
What is the difference between tonicity and osmolarity?
Osmolarity can describe the state of solution vs cell and vice versa
Tonicity describes the state of the solution ONLY
What does it mean physiologically if there is positive free water clearance?
This means the urine flow rate, V, is greater than osmolar clearance. Such that the urine being excreted is hypo-osmotic and dilute
What does it mean if there is negative free water clearance?
Means the osmolar clearance is greater than urine flow rate, V. Thus the excreted urine is hyper-osmotic and more concentrated compared to plasma
What is the fractional clearance of urea?
~ 0.2 - 0.6
Urea is a _______________ product of ___________________ metabolism. Made in the __________________ and released into circulation for excretion by the kidney.
Waste
protein
liver
Urea is small and thus: _____________ _____________ into the tubule. And cross the tubule wall via:
Thus the, the MORE water absorption =
Freely filtered
Passive movement across the tubule wall down its concentration gradient
the more water absorption means more urea reabsorption since the leaving of H20 concentrates the urine creating a concentration gradient
Normally urea excretion and fractional clearance of urea are both low due to:
This means the blood urea nitrogen is:
Large water reabsorption which urea follows
High
What does comparing the plasma creatinine and BUN allow us to do clinically?
Determine dehydration VS kidney disease
If both go up this means GFR is falled = CKD
BUN up only = dehydration
The comparison of plasma creatinine and BUN can indicate difference between dehydration and CKD, why?
Creatinine is an endogenous substance that can be used to calculate GFR
BUN indicates the amount of water being excreted/reabsorbed because urea excretion is opposite BUN. Urea excretion and fractional clearance correlates to water absorption/excretion.
If BUN and creatinine levels go up what does this indicate and why?
CKD
Because creatinine filtration is supposed to match excretion under normal GFR. If creatinine levels go up, then the GFR went down
If BUN only goes up, what does this indicate and why?
Dehydration
This is because urea effectively follows water absorption/excretion
If urea is up, then water absorption is up due to the body needing to hydrate itself with water available
Urea is _________________ in the PCT and inner medullary collecting duct. Urea can be ________________ into the thin ascending loop of Henle.
Reabsorbed
Secreted
Clearance of urea is always <, >, or = to the clearance of inulin. Why?
C urea < C inulin because all plasma inulin should be excreted while plasma urea will be reabsorbed following flow of water
The para-aminohippuric acid fractional clearance is:
What does this mean
~ 5.0
Means the PAAH is secreted into the tubule
Why is plasma clearance of PAAH (para-aminohippuric acid) equal to the renal plasma flow rate?
Because, all PAAH from the plasma is secreted into the tubule for secretion = the volume is corresponding to the amount of plasma flowing through the kidney
Why is creatinine fractional clearance greater than clearance inulin?
Because while they are both freely filtered and entirely excreted, there is some tubular secretion of creatinine into the urine which raises the fractional clearance
Inulin and _____________ are perfect markers for GFR calculation but are not clinically used because they are not endogenous
Iothalamate
Describe the concentration of sodium and potassium in the intracellular and extracellular compartments
What maintains this composition?
INTRAcellular: High K+, Low Na+
EXTRAcellular: High Na+, Low K+
Na/K ATPase
Describe the concentration of protein inside the cell, in the interstitium, and within the plasma
INTRAcellular: 30 g/dl
Interstitium: 1 g/dl
Plasma: 7 g/dl
How much Na is reabsorbed?
The majority of it, 99%
Where are the ONLY two places that Na+ transport does NOT occur?
Descending loop of Henle and Thin ascending loop of Henle
Where does bulk reabsorption of sodium occur?
In the proximal tubule
What stimulates sodium reabsorption in the PCT?
What inhibits sodium reabsorption in the PCT (minor role)?
Stimulate: alpha-adrenergic nerves & ANG II
Inhibited: Atrial naturetic peptide and nitric oxide
How many “Stages” of sodium transport exist in the proximal tubule?
2
Describe sodium transport at the Early proximal tubule
The NHE3 major transporter
1.) The cell generates a H+ inside the cell and exchanges this ion for a Na+ from the tubule lumen
2.) Electrically neutral exchange
3.) Na+ is removed and put back into the body (interstitum) via Na+//K+ ATPase
What is the primary absorptive mechanism of sodium at the early PCT?
Na+ - H+ Exchange aka NHE3
Where does the NHE3 transporter exist? What type of transport occurs here?
At the early PCT
Uses secondary active transport using the energy generated from the Na+/K+ transporter on the apical side of the tubule
In the early PCT, what is significant about the H+ ion secretion?
The H+ drives bicarbonate reabsorption
T/F: The early PCT only reabsorbs sodium via NHE3 transporters
False, sodium transport also coupled to glucose, amino acid, phosphate, and lactate absorption
Describe the movement of Chloride in the early PCT
Leaks through channels into the interstitium
Describe the movement of H20 and sodium at the early PCT
Iso-osmotic. Water follows sodium transport
Why does solute concentration fall moving down the PCT?
Because it’s all been absorbed early in the PCT
Describe solute movement at the late PCT
1.) H ion + waste anions form H anion and are reabsorbed
2.) The anion breaks apart in the cell to release a H+ and anion
3.) Outward moving H+ couples with Na+ exchange while anion couples with Cl- exchange, thus Na+ and Cl- going into the cell
4.) The concentrated Cl- tubular fluid drives Cl-/Na+ down its concentration via paracellular diffusion into the peritubular capillary
Describe sodium movement at the Loop of Henle
Nothing in descending or ascending thin loop of Henle
Thick ascending loop of Henle, 25% Na sodium reabsorbed
What stimulates sodium reabsorption at the loop of Henle?
What inhibits sodium reabsorption?
Stimulate: alpha adrenergic nerve, Angiotensin II
Inhibit: prostaglandin
List the two transporters responsible for sodium exchange in the thick ascending loop of Henle
1.) NHE3, minor contributor
2.) Sodium potassium 2 Cl- Co-transporter (major transporter)
What is the abbreviation for the sodium potassium, 2 chloride co-transporter present in the TALH
NKCC2 transporter
What drives the NKCC2 co-transporter in the TALH?
ROMK channels
Potassium channels that allow K+ to flow down its concentration gradient into the tubular lumen
How does Na, K+, Cl- get into the interstitium?
Na+/K+ ATPase
K+/Cl- co-transporter
Both on the apical side
Other than supplying K+ in the TALH, what else is significant about the ROMK presence on the luminal cell side?
It creates a small + charge within the tubule lumen
What is special about the NKCC2 pump?
It is involved in signal transduction at the macula densa
T/F: The thick ascending limb is the site of sodium and water reabsorption
False, sodium reabsorption only. Always Impermeable to water!
How much sodium is reabsorbed by the distal tubule?
What stimulates this absorption?
What inhibits it?
~10%
Stimulated by: Aldosterone and Angiotensin II
Inhibited by: Atrial naturetic peptide and nitric oxide
What is the major controller of how much sodium is reabsorbed at the distal tubule and collecting duct?
Aldosterone
What transports sodium from the lumen in the distal tubule?
The NCC co transporter
What is special about the NCC transporter? Where is it located?
Thiazide sensitive
Distal tubule for sodium and Cl reabsorption
How does Aldosterone increase sodium reabsorption at the distal tubule?
Increases the number of NNC transporters in the luminal membrane
Also increases ATP to increase Na/K ATPase activity for more sodium to go back into the interstitium
Can even increase quantity of Na/K ATPase pumps
List the two different cell types of the collecting duct
1.) Principle
2.) Intercalated cell
Describe the movement of sodium and potassium in and out of the lumen in the principle cells of the collecting duct
1.) Sodium flows down its concentration gradient through epithelial sodium channels
2.) Potassium leaks out of the principle cell down its electrical concentration gradient to balance the negative charge that was established by reabsorption of Na+
What is the name of the epithelial sodium channels found in the collecting duct?
ENaC channel
T/F: Amiloride affects the number of ENaC channels in the principle cells of the collecting duct
False, Aldosterone influences the number of ENaC channels and causes channels to shuttle to the luminal membrane
Aside from reabsorbing sodium as needed for the body, what is significant about ENaC channels and the absorption of sodium from the collecting duct?
The + charged sodium being absorbed into the cell on a large scale creates a negative lumen charge that drives the flow of K+ out of the cell
T/F: Similar to its influence on sodium reabsorption in the principle cells of the collecting duct, Aldosterone also influences the movement of water in the collecting duct
False, water reabsorption is influenced by ADH
What diuretic inhibits the NKCC2 transporter? Thus, where is this diuretic acting?
Furosemide (Lasix)
Acting Thick ascending loop of Henle
What diuretics inhibit the NCC transporter? Thus, where is this diuretic acting?
Thiazides and Metolazone
Acting Distal tubule
What diuretics inhibit the ENaC transporter? Thus, where is this diuretic acting?
Amiloride and Triamterene
Collecting duct
What does Spironolactone inhibit? What further implications does this have?
Inhibits the actions of Aldosterone by inhibiting the actions of the mineralocorticoid receptors
Thus blocks reabsorption in the Distal tubule and Collecting duct
Describe how diuretics that act ahead of the collecting duct can cause hypokalemia and potassium wasting
If there is blocked sodium reabsorption ahead of the collecting duct, once filtrate reaches the collecting duct ENaC will attempt to compensate and reabsorb more Na+ here which will make the tubule lumen more negative and thus driving K+ out of the cell for excretion
Why is Amiloride considered a potassium sparing diuretic?
Because it blocks sodium reabsorption at the collecting duct, thus preventing the electrical concentration gradient formation to drive potassium out of the cell and into the lumen
Why does the sodium concentration in the ECF remain fairly constant even if sodium amount changes?
A change in sodium content reflects subsequent change in fluid volume to maintain concentration
In negative Na balance: Output > intake. Na ____________ occurs and ECF volume ____________. Which can lead to circulatory collapse and organ failure
Depletion
decreases/falls
In Positive Na balance: Output < intake, Na _____________ occurs and ECF volume __________________. Which can lead to edema
accumulates
Increases
What is the basic premise of Glomerular tubular balance
Limits how much sodium is excreted
Describe how glomerular tubular balance works.
The increased sodium filtration would theoretically lead to increased urine excretion
With GTB, the PCT increases the amount of Na reabsorbed so that the PCT is always absorbing a CONSTANT FRACTION of the filtered Na
Since this is the largest site of Na reabsorption this protects excess excretion
What determines Sodium Excretion aka UNaV
Filtered Na - Reabsorbed Na
What are two mechanisms proposed to account for glomerulotubular balance?
1.) Luminal control
2.) Starling pressures
Describe luminal control and its relation to glomerulotubular balance
Flow dependent response/sensor at the PCT where increased Na delivery is sensed and automatically increases reabsorption of Na proportion
What are two mechanisms for sodium retaining? What activates these?
Act as vasoconstrictor & Change tubular Na reabsorption mechanisms
Renin angiotensin/Aldosterone system
Sympathetic nervous system
Activated by Sodium depletion
What are Naturetic systems? What activates these?
Activated by excess sodium, volume expansion, increased BP
Atrial natriuretic peptide and nitric oxide acting as vasodilators and increase GFR
Describe the activation of RAAS
1.) Fallen sodium reabsorption = fallen total body volume
2.) Sensed by granular cells and they release renin into the blood
3.) The renin is an enzyme that acts on angiotensin to convert it to ANG I
4.) Then ANG I is converted to ANG II by converting enzyme
Describe what happens to sodium excretion when GFR is lowered
Lowered GFR = lowered sodium excretion
Describe 3 mechanisms of action of ANG II
1.) Ang II acts on renal circulation to lower GFR
2.) acts on PCT and TALH to increase Na reabsorption
3.) acts on adrenal cortex to stimulate aldosterone
_______________ is a steroid hormone, (mineralocorticoid) made in the adrenal cortex
Aldosterone
T/F: Aldosterone not only influences sodium excretion but also, potassium and H+ excretion
False, it does increase K+ and H+ excretion but also sodium RETENTION
Explain how aldosterone physically acts on the principle cells of the collecting duct
1.) Aldosterone transports from the blood to the basolateral side of the principle cell
2.) Aldosterone interacts with mineralocorticoid receptor
3.) This aldosterone/mineralocorticoid receptors interacts with the nucleus
4.) Initiates transcription and protein synthesis
These proteins act in an immediate response
5a.) More open ENaC on luminal side
5b.) Proteins activate mitochondrial enzymes to make more ATP to increase Na/K ATPase
5c.) over days, larger quantity of Na/K+ ATPase pumps
What stimulates aldosterone release from the adrenal gland?
Increased plasma potassium increases aldosterone release
T/F: ANG II can DIRECTLY increase aldosterone release
True
Why is fallen plasma sodium level not considered a major contributor to aldosterone release?
Because the kidneys work to maintain constant plasma sodium levels, thus ideally this level will not waiver and NOT contribute aldosterone release
What controls ANG II release?
Renin release
What is stimulating the granular cells and subsequent renin release when baroceptors sense fallen renal perfusion at the afferent arteriole?
Beta adrenergic action stimulates granular cells
How does lowered afferent arteriole pressure influencing action at the macula densa?
If there is lowered pressure, there is lowered renal plasma flow and thus lowered filtration at the glomerulus. Thus less sodium is sent into the filtrate. The macula densa in the DCT senses this reduced sodium delivery
Once the macula densa senses a lowered sodium delivery at the DCT, this activates the Juxtoglomerular apparatus. Describe this mechanism of action
1.) The macula densa sends signals to the extraglomerular mesangial cells
2.) These cells signal to the granular cells to release renin into circulation
Describe the negative feedback mechanism of renin release
As plasma ANG II levels increase, there is feedback DIRECTLY on the granular cells to inhibit further renin release
What might hypoaldosteronism cause?
Disorders such as Addison’s disease
Sodium wasting and low ECF
What might hyperaldosteronism cause?
Sodium retention (on a short term bases) and volume expansion
What is mineralocorticoid escape?
It is induced during long term hyperaldosteronism. This will allow the tubules to escape/disregard the normal effects of aldosterone to prevent sodium reabsorption
What protects people with hyperaldosteronism from edema?
Mineralocorticoid escape
T/F: Due to the induction of mineralocorticoid escape a few days after onset of hyperaldosteronism, Na reabsorption, K+ & H+ excretion are all physiologically ignored
False, only applies to d/c Na+ reabsorption
____-adrenergic fibers supply the renal blood vessels and lead to vasoconstriction.
These fibers also supply the PCT and TALH and lead to increased sodium reabsorption
Alpha
What two types of fibers innervate the renal system under the sympathetic nervous system?
Alpha and Beta Adrenergic fibers
The beta adrenergic fibers influence renin release through stimulation of granular cells. How do alpha adrenergic fibers influence renin release?
The alpha adrenergic fibers decrease renal plasma flow and GFR
This decreases the NaCl delivery to the macula densa
This is sensed at the juxtoglomerular apparatus and stimulates granular cells and renin release
How does ANP (atrial natriuretic peptide) induce naturesis?
1.) increases GFR
2.) Acts directly on the collecting duct to inhibit sodium reabsorption
3.) Acts on adrenal gland to inhibit aldosterone release
Filter more and reabsorb less = Na excretion
How does Nitric Oxide (NO) induce naturesis
1.) Increasing GFR
2.) Acts on the collecting duct to inhibit renal sodium reabsorption
3.) Vasodilator
What induces Nitric oxide release?
High salt intake since NO is made in the blood vessel endothelium, volume expansion due to high salt intake stimulates release NO
What induces release of ANP (atrial natriuretic peptide hormone)
hormone made in the cardiac atria is released in response to ECF volume expansion based on the increase in R atrial pressure/atrial stretch
How do prostaglandins induce natruesis?
Not sure
Describe pressure Natriuresis
When is it induced?
Occurs within minutes corresponding to abrupt rise in arterial blood pressure
Increased BP inhibits Na-H exchange and Na+/K+ ATPase activity both to decrease sodium reabsorption and water reabsorption
List 3 major functions of calcium
1.) makes up bones and teeth
2.) nerve and muscle function
3.) intracellular signaling molecule
List 3 major functions of phosphate (PO4)
1.) Makes up bones and teeth
2.) Buffer
3.) makes up substances in the body
4.) phosphorylation involved in activation and inactivation of enzymes
What drives Calcium resorption from the body back into the bone?
PTH
Calcitriol
What directs the absorption of calcium into the body from the intestine?
Calcitriol
What directs calcium absorption into the bone?
Calcitonin
What influences calcium excretion from the kidney?
PTH
Calcitonin
Calcitriol
Where is most of the calcium in the body?
99% is in the bone
Of the 1% of total body calcium that is filterable through the kidney, what is the limitation of filtration through the glomerulus?
40% of the calcium is protein bound and thus too large to filter through the glomerulus
Of the calcium that is filtered, about 2/3 of the calcium is reabsorbed where? Is it active or passive reabosrption?
Proximal tubule
Coincides with the reabsorption of Na in the proximal tubule, passive reabsorption
In the ______ about 20-25% of ionized calcium is reabsorbed. Is this active or passive reabsorption
Thick ascending loop of Henle
Passive reabsorption driven by the + lumen electrical potential made by the K+ recycling
Describe the reabsorption of Calcium int he Distal tubule
Active transport
Regulation of luminal Ca channels
PTH predominantly drives Calcium reabsorption, where does it act?
TALH and distal tubule
Calciferol increases Ca reabsorption in the:
Calcitonin increases Ca reabsorption in the:
Both are more minor contributors
DCT
TALH and DCT
How does high plasma calcium inhibit Ca reabsorption in the TALH
By activating the Ca sensing receptor in the TALH
This inhibits the NKCC2 channel which decreases the + charge generated here by the K+ recycling
Thus less Ca is reabsorbed
_________________ has the same effect as high plasma calcium because this drug also block NKCC2 in the TALH
Furosemide
Persons at risk of Calcium stones are placed on thiazide diuretics, why?
Thiazide diuretics increase Calcium excretion by inhibiting NCC channels in the distal tubule. The mechanism is up for discussion, but since Na reabsorption is correlating to Ca reabsorption the Ca reabsorption is decreased
Where is the majority of phosphate (PO4) found?
85% in the bone
About how much of the total body phosphate is found in the extracellular space and thus filtered through the glomerulus?
Less than 1%
_________________ Drives phosphate reabsorption from the intestine
Calcitriol
What drives phosphate into the bone and soft tissue?
Calciton
What pulls phosphate out of the bone and soft tissue into the body and the kidneys?
PTH
Calcitriol
What influences excretion of phosphate from the kidneys?
Calcitonin and PTH
What inhibits phosphate excretion in the kidneys?
Calcitriol
Describe the reabsorption of phosphate at the PCT
Co transports with sodium via active processes meaning it is saturable
T/F: Phosphate is not normally excreted in the urine since only 1% of the total body phosphate is filtered in the kidneys
False
What does PTH do in the PCT in regard to phosphate reabsorption
Since reabsorption is an active process here and can be saturated PTH works to lower the transport maximum and thus makes saturation occur sooner
LOWERS phosphate reabsorption
_____ is a “nonreabsorbable anion” in the collecting duct and contributes to lumen negativity in the collecting duct
PO4
Lowered GFR = _____ Plasma phosphate
Increased plasma phosphate
What is concerning about increased plasma phosphate levels?
It can form complexes with calcium and be problematic in other body systems
Increased plasma phosphate levels will induce:
Higher levels of parathyroid hormone and secondary hyperparathyroidism
In terms of hemorrhage, once blood loss exceeds 10% of total volume. The _______ system is activated to increase water retention and at high levels as as a vasoconstrictor
ADH
Hemorrhage greater than 25% total blood volume starts to see reduced organ involvement and ___________ ___________ _________. In this scenario, the ______________ systems are exceeded capacity. And can lead to Hemorrhagic shock
Acute renal failure
Vasoconstrictor
What is the long term solution to 25% reduction of blood volume in hemorrhage?
Only answer is replenishing blood volume. SNS, &RAAS etc are only sustainable for a limited time
_________ _______ is caused by bacterial infection in blood. Massive vasodilation and falls in BP which send volume depletion signals. This causes renal sodium retention and increases in ECFV. The bacteria endotoxin also:
Septic shock
Causes capillary leak where fluid and protein leaves the circulation and enter the interstitium causing severe edema
List two conditions that can cause underfill of vascular volume but overfill of extracellular fluid volume. Why don’t inhibitory signals help reduce this condition?
1.) Liver cirrhosis
2.) Nephrotic syndrome and there is loss of protein that plasma protein falls. This causes fluid to accumulate in interstitium
Kidney becomes unresponsive to NO signaling that would normally reduce sodium absorption
Why/how does glucose cause an osmotic effect?
There is an excessive amount of glucose that is being allowed into the tubules. These tubules will attempt to reabsorb the glucose. The remaining glucose will accumulate in the tubule which will pull water out of the body
Salt sensitive hypertension is always associated with a ______________ of the acute pressure naturesis
Suppression
So kidneys will be very slow at inducing salt removal from the body
Describe acute pressure naturesis
As the arterial pressure rises, in healthy individuals, the kidney will remove more and more salt to help the body remove excess fluid volume
Short term solution
1.) Describe the changes in renal function curve for essential hypertension in NON salt sensitives.
2.) What about salt sensitive?
3.) What about people who are normotensive
1.) The arterial pressure will have a broader and higher pressure to reach before the kidneys start to remove sodium
2.) Blood pressure goes up as salt intake goes up & salt intake must be lowered significantly before arterial pressure lowers
3.) Smaller changes in arterial pressure will induce naturesis and the kidneys will excrete much more sodium to maintain a lowered pressure
The passive diffusion of ____ out of all cells creates a membrane potential. This is why ____ is at higher levels inside the cell
K+
What causes flaccid paralysis?
Too low of K+ within the cell so there is hyperpolarization that makes it harder to depolarize the cell
What causes spastic contraction of muscle?
A state of hyperkalemia within the cell will slightly depolarize the cell making muscle contraction easier
Name three systems that are put in place when there potassium levels rise and to pull potassium into the cell
1.) Insulin (Most imp)
2.) β adrenergic agonist
3.) Aldosterone release
What does α-adrenergic stimulation do to potassium levels?Wah
Promotes movement of potassium out of the cell
What does increased pH (alkalosis) do to potassium levels?
Induces K+ entry into cells in exchange for H+ to help bring pH down
When the body is in an alkaline state, the body will go into ____________________ with ________polarization
Hypokalemia
Hyperpolarization
List three types of drugs that can induce hyperkalemia
1.) ANG II and aldosterone inhibitors
2.) K+ sparing drugs
3.) β Blockers
List two types of drugs that can induce hypokalemia
1.) K+ wasting drugs
2.) β-adrenergic agonists
T/F: To protect against hyperkalemia, the body filters lots of K+ at the glomerulus
False, very little is filtered
Where does the determination of final Urine potassium levels occur?
Mostly reabsorbed in the collecting duct
Some recycling at the TALH
Secretion varies at the Collecting duct
T/F: Most potassium is reabsorbed in the kidney under normal circumstances
True
Describe K+ recycling in the TALH
The NKCC2 channel needs to pull K+ and Na+ into the cell. Since the K+ levels are normally low in the ECF/Lumen, the ROMK channel pumps K+ out of the cell to allow the NKCC2 to function
What is the importance of intercalated cells and where do they exist?
Pertain to acid base balance
In the Collecting duct
In the intercalated cells of the CDT, exists the ______________________________ to reabsorb potassium if needed
K+/H+ ATPase which pushes K+ into the cell in exchange for H+
K+ moves against or with against the concentration gradient and electrical gradient when describing the ICF
K+ moves down the concentration gradient from [H to L]
K+ moves down the electrical gradient from [H to L]
Anything that promotes ____________ intracellular potassium will induce:
Higher concentration
K+ secretion
What is the main hormone controlling potassium secretion
Aldosterone
Does hyperkalemia or hypokalemia induce aldosterone release? Why
Hyperkalemia
Aldosterone will promote K+ entry into cells to pull K+ out of the plasma by stimulating Na+/K+ ATPase
Stimulates ENaC that is stimulating Na+ reabsorption from the lumen to make lumen more - to drive K+ into the lumen for excretion
Stimulates luminal potassium channels
How does the presence of non-reabsorbable anions induce K+ secretion?
What are some examples of these non-reaborbable anions?
PO4 or HCO-3 in the lumen are -
This overall negative charge draws the K+ down its electrical gradient into the lumen
What is normal total renal blood flow
1.2 L/min
About how much of the cardiac output is directed to the total renal blood flow
25%
Why is there a fall in blood pressure when the blood arrives at the cortical, radial, and afferent arterioles?
Because they are resistance vessels
Is the glomerular a low or high resistance site? What does this mean in regard to the blood pressure?
Glomerulus is low resistance so there is very little reduction of blood flow along the length of the glomerular capillary
What maintains the glomerular pressure?
Glomerulus has 55 mmHg because the resistance vessel, efferent arteriole, provides a backpressure
What is EXCLUDED from the glomerular filtrate?
Proteins and Blood cells
What makes anions less filterable compared to cations at the glomerulus?
Endothelial cells are lined with negative charges that repel the anions in the blood flow being
What is significant about the glycocalyx?
Its mesh like netting that stretches across the spaces between first layer of Bowman’s capsule to prevent proteins from being filtered
About how much of the total body weight is water?
60%
About how much of the total body weight is water of the interstitial fluid?
40%
About how much of the total body weight is water of the extracellular fluid?
20%
Decreased ______________ and _____________ osmolality stimulate central receptors, more specifically the hypothalamus to initiate true thirst
Volume
Increased
About _____% of filtered water and sodium are reabsorbed at the PCT
65
Why does osmolality remain about the same as plasma osmolality at the PCT?
Because for each water fluid reabsorbed a salt reabsorbed with it
Describe the movement of solutes and water in the descending loop of Henle
Does this affect osmolality?
No active transport
Permeable to water, reabsorption
Yes, makes the fluid in the lumen more concentrated
Describe the movement of solutes and water in the thin ascending loop of Henle
Does this affect osmolality
No movement
No change in osmolality
Why is the TALH osmolality/solute concentration drop?
Sodium reabsorption here which is impermeable to water
Describe the osmolality composition at the end of the TALH
Osmolality is below plasma osmolality
Describe the movement of solutes and water in the thin ascending loop of Henle
Does this affect osmolality?
More sodium reabsorption and impermeable to water
Yes, further reduces osmolality and become more dilute
Where does ADH aka vasopressin act in the nephron?
At the collecting duct
If there is no ADH at the collecting duct, what will happen?
Impermeable to water, no water reabsorption
Reabsorption of sodium via ENaC here = even more dilute urine
ADH:
Aldosterone:
Water reabsorption @ collecting duct
Salt reabsorption @ collecting duct
When there is ADH present, what will happen?
Collecting duct permeable to water so osmolality can be very high
Whatever the final urine concentration and volume the following always applies:
The fluid entering the cortical collecting duct is always dilute relative to the plasma
Where is the only place in the body that does not have osmotic equilibrium?
The kidney medulla and interstitial fluid here
What is the countercurrent multiplication of a single event?
How the NKCC2 of the TALH reabsorbs sodium. Some of this sodium gets trapped in the interstitial medulla. Which is in part driven by the water that was reabsorbed in the descending loop of Henle
When does urea recycling occur?
Where does urea recycling occur?
Only in the presence of ADH
Papillary collecting duct urea diffuses out
Passive inward diffusion in THIN ascending loop of Henle since some urea was trapped in the papillary interstitium
How is the interstitial concentration gradient maintained through vasa recta blood supply?
The vasa recta blood flow is slow
Countercurrent exchange
Countercurrent multiplication creates:
Countercurrent exchanger creates:
1.) Creates the medullary interstitial concentration gradient via tubule
2.) Maintains the concentration gradient and prevents washout via vasa recta
Describe the counter current exchanger
What is important about the countercurrent exchanger:
The medulla needs to be perfused with blood, but since the blood osmolarity is lower than the medulla there is risk the blood will reduce the concentration. The countercurrent exchanger prevents this
Normally people are in danger of _______________ because of ingesting food. There is continual production of organic _______ which are metabolized to CO2 and excreted via the lungs
Acidosis
Acids
__________________ are unable to get glucose into the cell for use as an energy source. So the body uses _____________metabolism that makes keto acids. This overloads the metabolic capacity at the liver which allows for accumulation of acids in the body:
Diabetics
lipid
Ketoacidosis
What are fixed acids and how are they normally excreted?
Fixed acids made from protein metabolism
Excreted via urine
What is the major contributor of acids in the body?
What is the minor contributor?
Major: organic acids from food
Minor: Fixed acids from protein metabolism
Name the immediate body response to acid buffering
Rapid buffering
Name the intermediate response to acid buffering
Respiratory compensation via control of the total CO2 content
Name the long term response for acid buffering
Renal compensation
What are the basic tenants of acid renal compensation
Removal of excess H+ and regeneration of base in form of HCO3 (bicarb)
Describe rapid buffering
Ions, compound, anion proteins are circulated throughout the body and adjust within milliseconds-minutes to buffer acids that are constantly being produced
HCO3 is an important _________________ buffer.
Negatively charged proteins buffer in _____________ and ________________
CO3 in bone provides:
1.) Extracellular buffer
2.) Plasma and intracellular
3.) provides an intracellular buffer store that can be released into the ECF
Describe how acidosis can impact potassium levels
Potassium is normally highly concentrated within the cell
In states of low pH the H+ can be exchanged into the cell for a K+ moving outside the cell
If there is too large a reduction in intracellular K+ this will depolarize the cell wall allowing the cells to be too easily excitable and spasm and potassium excretion will be reduced at the collecting duct
While K+/H+ buffering is an acute response to acidosis, longer term high levels of K+ will cause:
Stimulate release of aldosterone to encourage secretion and subsequent excretion of K+ from the principle cells of the collecting duct
Describe the bicarbonate buffer system:
H+ + HCO3 ↔ H2CO3 ↔ H20 + CO2
H+ & bicarb ↔ carbonic acid ↔ H2O to CO2
Carbonic acid to water and carbon dioxide requires carbonic anhydrase for rapid breakdown
Why can the bicarbonate buffering system via respiration be exhausted?
Because, the system favors CO2 production. Each time, this uses 1 H+ (good) and 1 Bicarb (HCO3 & needed)
When plasma CO2 levels rise what will happen?
1.) CO2 sensitive chemoreceptors will stimulate inc. respiration
2.) The reduction in plasma pH will stimulate indirect response to inc. respiration
How does the kidney provide long term restoration of pH balance?
1.) Makes bicarb HCO3
2.) Conserves HCO3 through reabsorption
Where are sights of H+ secretion along the tubule?
Largely in the PCT & TALH
Minimal in the Collecting Duct
Bicarbonate is filtered into the kidney. How is it reabosrbed?
H+ secretion at the PCT and TALH drives HCO3 absorption
How does the PCT generate H+ ion to drive Na+ absorption and H+ secretion?
CO2 + H2O → Carbonic Acid → H+ & HCO3-
The H+ is driven out of the cell into the lumen by the Na/H+ exchanger and the HCO3- flows down its concentration gradient into the blood
T/F: The H+ moving out of the cell drives HCO3 into the cell out of the lumen of the PCT & TALH
False, there is no mechanism for HCO3, that was filtered through the glomerulus into the lumen, to be directly absorbed into the cell
The Bicarb that is absorbed here is generated intracellularly
Describe HCO3 reabsorption mechanism at the TALH and PCT
The H+ that is excreted into the lumen combines with the HCO3- of the filtrate
This forms carbonic acid, H2CO3-
There is carbonic anhydrase lining the luminal cell membrane.
This converts the the carbonic acid into H20 & CO2 which can diffuse into the cell to make HCO3 INTRAcellularly
T/F: The mechanism to reabsorb Bicarb at the TALH and PCT is saturable
True
What is different about the HCO3 regeneration at the Collecting duct compared to TALH & PCT? (2)
1.) There is no carbonic anhydrase at the brush border of the luminal side of the cell so converting the Bicarb & H+ to H20 & CO2 is fairly slow in the collecting duct
2.) Since the majority of the bicarb is gone by the time reaching the collecting duct, the H+ will need to combine with a different buffer. Some of that includes HPO4
What is different about the H+ secretion at the Collecting duct compared to TALH & PCT?
H+ ion enters via H+/ATPse or by H+/K+ ATPase
Nephrogenic diabetes insipidus means:
How does this affect plasma and urine osmolality
The collecting duct cannot reabsorb water
Plasma osmolality high
Urine osmolality low
Low pCO2 causes:
Alkalosis `
How to calculate the GFR?
[ Urine inulin / Plasma Inulin ] * Urine flow = mL/min
How to calculate est. Renal Plasma Flow
[ Urine of substance mg/mL / Plasma of substance mg/mL ] * Urine flow = mL / min
How to calculate the filtration fraction and what is it?
The fraction of the renal plasma flow filtered across the glomerulus
GFR / RPF
What is used to calculate the renal plasma flow? Any why is it used?
PAH, Because it is almost entirely cleared from plasma during 1 pass through the kidney
While 99% of protein is not filtered through the glomerulus, what about the 1% that makes it to the tubule?
Once the protein reaches the collecting duct, the proteins are absorbed, degraded within the cell to AA that are returned to the circulation via peritubular capillar
When there is heavy proteinuria, what happens to the plasma protein level?
The liver cannot synthesize enough protein and plasma protein goes down
Hydrostatic pressure of the blood causes:
Colloid osmotic pressure (aka oncotic pressure) of the proteins causes:
Filtration (moving fluid out)
Absorption from the ECF
When proteinuria occurs, how does this affect the colloid osmotic pressure (oncotic pressure)
The subsequent plasma protein fall lower the colloid osmotic pressure that disallows absorption of ECF and can cause edema
In the capillary, there are driving pressure acting across the wall of capillary, hydrostatic pressure:
Colloid osmotic pressure:
Fluid pressure of blood trying to push water OUT
Due to plasma protein trapped inside the capillary trying to pull water IN
At the arterial end of a capillary the pressure is normally ___________. Why?
To force water nutrients out and into interstitial space
As blood moves down the capillary, hydrostatic pressure _______________ and loss of water by filtration at this point causes the colloid osmotic pressure to ______________. This allows:
Falls
Rises
Uptake of fluid from the interstitial to deliver waste products
Glomerular blood pressure is ___________ at ~ 55 mgHg.
Since Bowman’s capsule is fluid filled:
The difference between P glomerulus capillary - Pressure Bowmans capsule does what?
High
It exerts a pressure back ~ 10 mmHg
Drives and determines filtration
What is the glomerular oncotic pressure ( colloid osmotic, )?
What is the Bowman’s colloid osmotic pressure?
1.) The pressure exerted by proteins of the plasma that increases moving from afferent to efferent arteriole due to the loss of water
2.) There is no colloid osmotic pressure in Bowman’s space since no protein is filtered through the glomerulus
T/F: The pressure lowers are the blood moves through the glomerular capillary because the water is filtered out and volume decreases
False, because the vessel is low resistance the pressure stays the same
When does filtration cease as plasma flows through the glomerular capillary?
When the [Pgc - P bs] aka ΔP is EQUAL to the oncotic pressure of the glomerular capillary moving towards the efferent arteriole as water is filtered into the tubule
Filtration is = Absorption
The greater the renal plasma flow:
The greater the glomerular filtration rate
What is the filtration fraction?
The percentage of water that is driven out of the renal plasma flow as it passes through the kidney
Why does increasing filtration fraction increase the GFR without changing the renal plasma flow?
The same amount of plasma is flowing but if more water is being filtered out and into the glomerulus, then the glomerular filtration rate will increase
Changes in GFR can be regulated by:
Renal plasma flow
Fraction filtration
or both
What is the MOST important component effecting GFR?
Renal plasma flow because at lower volume of plasma being delivered to the glomerulus allows the oncotic pressure and hydrostatic pressure to be equalized sooner
Renal plasma flow is controlled by changes in:
Afferent and efferent arteriolar resistance
Relaxation of renal afferent and or renal efferent arterioles will:
Why?
Increase RPF
Both are relaxed so flow increases
If afferent artiole resistance increases, what happens to the Pressure of the glomerular capillary?
Pressure drops
If efferent arteriole resistance increase what happens to the Pressure at the glomerular capillary?
Glomerular pressure rises because there is back pressure onto the glomerular capillary
If there is increased resistance of afferent and efferent arterioles, what happens to glomerular capillary pressure?
Nothing, since the changes are same on start and end
What is Kf and why is it significant?
Kf = filtration surface area * water permeability
It can influence glomerular filtration rate
Tone in the ___________ ______________ ______ determines Kf via regulation of glomerular filtration SA. Normally these are relaxed so Kf is high enough so that it doesn’t influence GFR much
Glomerular mesangial cells
Normally renal nerve activity is low. What happens when renal nerves are stimulated?
What normally stimulates renal nerve activity?
Overall lowered GFR. The nerves cause constriction of afferent and efferent vessels, such that renal plasma flow is reduced and thus GFR is released
Stimulated by low volume/Low BP or need to reduce GFR
How does Ang II at higher levels raise Pressure of the glomerular capillary?
The Ang II vasoconstricts both afferent and efferent capillaries but prefers the efferent capillary. This increased resistance places back pressure on the glomerular capillary and causes increased Pressure at glomerular capillary when blood pressure is reduced
What does increased nitric oxide do?
Vasodilates the afferent and efferent vessels and relaxes the mesangial cells to raise RPF and thus raising GFR
Why are COX inhibitors need to be used with caution in older adults?
With age, GFR naturally falls.
To supplement, prostaglandins vasodilate to help raise GFR
Thus if using COX (a type of prostaglandin) inhibitor this can decrease GFR further
ANP is a ________________ and has _________________ effects. How does it work?
Vasodilator
Natriuretic (increase sodium excretion)
Dilates afferent artiole increasing Pressure of glomerular capillary and plasma flow = Inc GFR & inhibits sodium reabsorption
________ _____________ ____________ & ____________________ causes vasdoilation of both afferent and efferent resistance, thus increasing RPF & GFR
High dietary protein
Pregnancy
How does the kidney maintain constant GFR in the setting of fluctuating BP?
In heightened BP, the afferent arteriole constricts to maintain to maintain RPF and pressure of glomerular capillary
Name the two mechanisms of renal autoregulation
1.) Myogenic mechanism-fast requiring no nerve input
2.) Tubuloglomerular feedback
What is tubuloglomerular feedback?
A form of renal autoregulation at the juxtoglomerular appratus where the macula densa in the TALH and DCT contacts with the afferent arteriole
Renal blood flow supplies oxygen for renal metabolism. Renal O2 utilization is regulated according to energy requirement. What is the main energy requiring process in the kidney?
Active sodium reabsorption at the tubules
Why is it that oxygen extraction stays the same with increased Na absorption despite it being a large energy requiring event.
Increased Na absorption is equivalent to inc. GFR and RPF
Thus, while more O2 is needed and being extracted from the blood, more O2 overall is being delivered so the extraction matches what is being delivered
As GFR ___________________ the plasma creatinine _________________. The normal plasma creatinine is normally:
Falls
Increases
Normally plasma creatinine is low
What is a contributing factor to progressive glomerular injury?
Long term increased glomerular pressure damages glomerular capillary
Why are ACE inhibitors considered to be renal protecting?
Because they inhibit ANG
The continuous elevation of ANG will vasoconstrict to raise pressure of glomerular capillary and damage it leading to CKD
