Normal Renal Str and Func 1-Wall Flashcards
What is the main job/function of the kidney?
To maintain homeostasis for a large number of solutes and water despite variations in endogenous production and dietary intake.
What is homeostasis?
Maintaining body contents at a stable and normal level, even in the face of changes in dietary intake or endogenous production rate.
How does the kidney keep the total body content at a stable normal level?
By changing its rate of excretion.
What is the key solute of renal physiology and what fluid compartment is it restricted to?
Na+; restricted to the extracellular space
What determines the size of the ECFV, and what ECFV determine?
total body sodium content determines ECFV, which determines Blood volume/BP
No Sodium→No ECFV→No BP→No LIfe
The kidney links virtually every homeostatic function to what?
the renal handling of sodium
What is the main extracellular osmole? What is the main intracellular osmole? What is the relationship between intracellular and extracellular osmolalities?
EC→Na+; IC→K+; they are always the same
What determines the size of TBW? How does it do this?
TBNa+;
Increased TBNa+→increase osmolality→stimulates thirst→increase water intake and stimulate vasopressin secretion→tells kidney to conserve water
What is major anion of the extracellular space? What is the other major anion?
Cl-; Bicarbonate (HCO3-)
What maintains our TBW at a normal level? What percentage of BW is TBW? Is it higher in males or females? Why?
The kidneys maintain constant, normal TBW, regardless of how much is consumed; TBW=60% of BW in males and 50% of BW in females; higher in males bc females have lower skeletal muscle mass
What is the major ECFV buffer? What process does it play a key role in?
Bicarbonate; acid-base balance
What regulates Bicarbonate and to what level?
The kidney is involved in regulating bicarbonate at a normal level which assists in keeping the body pH at a normal level (7.4)
What are some major minerals that kidneys maintain homeostasis of?
Calcium, Phosphate, Magnesium
What are some wastes that the kidney eliminates and where do they come from?
Urea (byproduct of protein metab), Creatinine (byproduct of muscle metab), Uric acid (byproduct of nucleic acid breakdown)
What are some endocrine functions of the kidney? (4)
EPO production, 1-alpha hydroxylase to produce 1,25-dihydroxyD3 (activation of Vit D), Renin production, various paracrine/autocrine functions
How does reduction of functional kidney mass affect red cell production and what is the result?
The kidney is virtually the only source of EPO., which stimulates the BM to produce RBCs (reticulocytes);
Less functioning kidney mass→less EPO production→low reticulocyte count with normochromic normocytic anemia
How does reduced nephron function effect Vitamin D activation?
The kidney is virtually the only source of 1-alpha hydroxylase, the final enzymatic step in production of active form of Vitamin D (calcitrol);
Less Nephron function→less enzyme→Less of the active metabolite of VIt D
What is the only source of renin? Where is renin produced? What does renin start off?
only source is the kidney; renin is produced at the juxtoglomerular apparatus by specialized cells in the afferent arteriole it is the catalytic enzyme that kicks off the angiotensis-aldosterone cascade
What are the paracrine/autocrine functions of the kidney that are important in the kidney itself? (3)
bradykinin, prostaglandins, endothelial factors
What kind of substance is bradykinin?
It’s a vasodilatory, natriuretic substance
What is the significance of paracrine PG’s in the kidney?
PG production is critical in the autoregulation of GFR; especially the vasodilatory PG’s, PGI2 and PGE2
What are the important paracrine endothelial factors (produced by endothelial cells) in the kidney and what are their characteristics?
- Nitric Oxide→vasodilator
2. Endothelin→potent vasoconstrictor produced when there is endothelial injury
How does the kidney maintain normal BP?
A. By maintaining homeostasis of Na and water, which maintain normal ECFV, which determines BP
B. By controlling the RAA axis
C. Production of circulating vasodilatory substances, predominantly from the renal medulla
What do Ang-II and Aldosterone do?
Ang-II is a potent vasoconstrictor, aldosterone promotes Na+ reabsorption
Hypertension is largely a _________ disease?
Kidney disease; most examples of hypertension come back to dysfunction at the kidney level in one way or another.
What are some additional functions of the kidney? (3)
- Catabolism of small peptide hormones, such as insulin
- Production of glucose via gluconeogenesis during fasting
- Bc it is an excretory organ, it’s responsible for elimination of many medications.
How are the insulin requirements of diabetics affected by progressive kidney disease?
Decreased nephron mass→ slower degradation of insulin; So, insulin requirements decline in diabetics with progressive kidney disease, as the exogenous and endogenous insulin will last longer
How much gluconeogenesis can the kidney provide during fasting? What does increased incidence of fasting hypoglycemia sometimes lead to?
can provide up to 1/4 to a 1/3 of gluconeogenesis during fasting; sometimes leads to very low GFR.
People on medications with chronic kidney disease are at increased risk of what?
They are more susceptible to risk of high drug levels and potential toxicity with normal dosages.
What is the concept of balance?
How the kidney performs homeostasis
What is a neutral balance?
State in which dietary intake and endogenous production exactly match the excretion rate of the kidney; total body contents of the substance remain stable
Positive Balance?
Intake+Endogenous Production > Renal Excretion rate (kidney output); leads to increased total body content
Negative Balance?
Intake+Endogenous Production < Renal excretion rate; leads to decreased total body content
In any clinical content, to know if the kidney is working properly, what you should you do?
Examine the urine contents
a) If total body excess, the kidney should be doing what?
b) If total body deficit, the kidney should be doing what?
a) excreting
b) conserving
How much ultrafiltrate is is formed at the glomerulus each day in a normal male? What drives the filtration of such massive quantities of glomerular ultrafiltrate?
180L/days; simple starling forces at the glomerular capillaries (primarily high glomerular capillary pressure)
How does the osmolarity of the ultrafiltrate compare to the plasma? What is different about it’s composition compared to the plasma?
it is iso-osmolar to plasma; it is cell-free and protein-free
What is required for the formation of such a huge ultrafiltrate?
An enormous amount of blood flow to the kidneys; Each kidney gets about 10% of the total cardiac output to do this
How much of the glomerular filtrate must be reabsorbed? Why?
98-99% must be reabsorbed in the tubules; if not you would go into shock
How do the kidneys keep total body contents constant?
Selective reabsorption and selective secretion in tubules alter urinary excretion rates to keep total body contents constant
What is the major site of oxygen/energy consumption in the kidneys? Why?
renal tubules; it’s an enormous workload to reabsorb ~178L/day
If the body only makes 1-2L of urine a day, how does the kidney maintain homeostasis?
it ensures that the urine has precise amount of solutes and water to maintain homeostasis
What two parts of the kidney must work in concert to achieve normal kidney function?
glomerulus and tubules (filter and then reabs/secrete)
What is the best overall index of kidney function? Why?
glomerular filtration rate (GFR); most other kidney functions (endocrine and BP control) correlate with GFR
Low GFR→Reduced # of functioning nephrons→ impairment of homeostatic/endocrine functions
What four processes are involved in renal function?
- Glomerular filtration 2. Reabsorption 3.Secretion 4. Excretion
In reabsorption, what moves from where to where?
In reabsorption, certain solutes and water move from tubular fluid into peritubular capillaries and back into the circulation
What happens in secretion?
Addition of certain solutes (NOT WATER) to the fluid in the tubules from the peritubular capillaries
Removal of daily intake of what ion primarily occurs mainly thru a tubular secretory process?
potassium
Where are the kidneys located in the body? At what vertebral level?
retroperitoneum; about the level of T12 to L3
What is the kidney surrounded by?
it is surrounded by a tight fibrous capsule, which itself is surrounded by peri-renal fat
Where does the renal cortex reside? How much blood does it receive? What is located in the renal cortex?
Renal cortex is located just beneath the fibrous capsule and it receives 90% of the total blood flow to the kidney (90% of 10% of the CO); All of the glomeruli reside in the renal cortex
What structures are located in the renal medulla? What does it end in?
It has tubular structures, loops of henle, CD’s, and vasa recta; renal medulla ends in renal papillae
What pass thru the Hilum of the kidney contain?
renal artery, renal vein, renal pelvis, ureter, renal nerves, lymphatics, and they are all enmeshed in sinus fat
Once urine is formed, describe the path that it takes to reach the ureter:
exits at renal papillae→thru minor calyces→ come together into major calyces→ coalesce into renal pelvis→RP joins ureter
Describe the path of the ureter.
What is the general function of the bladder?
renal pelvis joins ureter→ descends in the retroperitoneum→crosses over the pelvic brim across vasculature structures→down into urinary trigone of bladder, which functions as a storage until voluntary voiding
What are the three main sites of potential obstruction by a kidney stone in the ureter?
- Pelvic-ureteral junction
- Crossover of pelvic brim
- Urinary trigone (bladder entry)
How does the female urethra differ from the male urethra?
It is shorter and at increased susceptibility to UTI and cystitis
What are the main agents that cause UTI’s? How?
Gram negative bacteria; they ascend urethra into bladder
What is different about the male urethra compared to that of a female?
Male urethra is longer and at less risk for UTI, but it has to pass thru the median lobe of the prostate
What is the most common spot for urinary obstruction in males? Why?
the prostatic urethra because every male’s prostate enlarges with aging (benign prostatic hyperplasia)
Describe the renal arterial circulation path:
Renal A→ 3-5 segmental and lobar aa→ Interlobar aa which ascend the medulla between the renal pyramids and reach the corticomedullar junction→Arcuate aa→Interlobular aa (perpendicular arteries that branch off ascending toward the renal capsule)→Afferent arteriole→Glomerular capillary network→Efferent arteriole→peritubular capillaries
What happens if there is a vascular injury to one of the arcuate arteries? Why?
the portion of the cortex that that arcuate artery provides is at risk for infarction because it is an end artery
How is the renal vascular tree different from normal circulation? Why is this important?
The vascular tree reforms another arteriole leading to a second set of capillaries→ this allows it to have both pre- and post-glomerular resistance vessels (afferent and efferent around the glomerulus)
What does a nephron consist of? What are the two types of nephrons and what are their relative frequencies and sizes?
a glomerulus and a tubule;
- Cortical nephrons (85%), smaller
- Juxtamedullary (JM) nephrons (15%), larger
Which type of nephron is further from the aorta, what does this result in?
Cortical; so, arterial perfusion to cortical nephrons is lower→so pressure inside their glomerular capillaries is lower→their filtration rate is lower
Compare the L of H of the two types of nephrons. Why is this important?
Cortical L of H is shorter; JM L of H is longer some will descend to the renal papillae→this is a critical part of the urinary concentrating mechanism
Compare the location of the two types of nephrons?
JM nephron glomeruli are located closer to the corticomedullary junction, while the cortical nephrons are located higher in the cortex
IMPORTANT: do the cortical nephrons operate at 100% capacity? Why is that important?
No, they are never operating at 100%. This allows for reserve capacity of the kidney so it can respond to abnormal circumstances. Ex: if you eat a high protein meal, GFR goes up 20% bc of reserve capacity.
When a person donates a kidney, why does their GFR not drop from 100% to 50%?
When a person donates a kidney, their GFR drops from 100 to 75% instead of 50%, because the reserve capacity of the cortical nephron allows their single kidney to compensate
What does the efferent arteriole of cortical nephrons form? What does it surround?
becomes the peritubular capillary which surrounds PTs, DCTs, and CCD’s
What percent of RBF goes to cortex and medulla?
90% of blood goes to cortex, 10% goes to medulla
Why is the filtration rate higher in JM nephrons?
closer to aorta→perfuse at slightly higher pressure→glomerular capillary pressure is higher→ GFR is higher
What is critically linked to the long JM nephron L’s of H?
maximal water conservation making maximally concentrated urine is critically linked to them
What is the major site of Na reabsorption? Why is this important? (2)
Medullary TALK; important for maximal Na conservation and for producing the hypertonic medullary interstitium
What is the only arterial blood supply of the medulla? What gives rise to it?
Descending vasa recta; efferent arterioles of JM nephrons
Why is it useful that only 10% of blood goes to the medulla?
Bc the medulla is hypertonic, and if we send large amount of blood to medulla, it will wash out the medullary solute, and we will be unable to make concentrated urine. It will be no more concentrated than the medullary interstitium, as water can only move by diffusion, not active transport.
What is the result of the vasa recta following the loops of henle?
a countercurrent arrangement
How does the countercurrent arrangement work? What is it important for?
there can be solute transferred between ascending and descending vasa recta, which is important for maintaining medulla in a hypertonic fashion
Why is the medulla susceptible to ischemic injury?
Oxygen is transferred between the asc and decs vasa recta. When it descends toward the tip of papillas, the O2 tension declines and leaves the medulla susceptible because it is getting progressively more hypoxemic
What do the efferent arterioles of the cortical nephrons form?
the peritubular capillaries that surround the PCT and all the other tubular structures in the cortex
Why are the JM nephrons at increased risk from hemodynamic stress?
bc they are always operating at full capacity
What is the glomerulus?
An invagination of capillaries surrounded by the fibrous Bowman’s capsule
What lines bowmans capsule?
parietal epithelial cells
What lies between B’sC and the glomerulus? What is it contiguous with?
The urinary space, which is contiguous with the beginning of the proximal tubule
The complex capillary wall of the glomerulus is made of what 3 structures? What is its purpose?
endothelial cells,
GBM→type IV collagen
delicate foot processes/slit diaphragms of visceral epithelial cells (podocytes);
purpose→to keep large proteins and cells inside the capillary and in particular to keep albumin, the most abundant serum protein, in the plasma and out of the urinary space
What two characteristics of the glomerulus result in its high filtration rate?
- Glomerular capillaries have an enormous surface area
2. They are perfused at slightly higher pressures than normal capillaries →hydrostatic pressure favors filtration
Why is the glomerular capillary wall highly permeable?
endothelial cells have more and larger fenestrae for filtration
If albumin is small enough to pass thru the capillary wall, why does it usually not?
The foot processes are negatively charged and because albumin is a polyvalent anion (multiple negative charges), it’s repelled and maintained in the vasculature
What surround every glomerular capillary?
lined up (interdigitated) foot processes from visceral epithelial cells (podocytes)
Where does the filtrate go once it is formed in the urinary space?
proximal tubule
What is the mesangium? What is it composed of?
ground material holding the glomerular capillary loops in the proper position (structural support); composed of mesangial cells and mesangial matrix
What are the two special functions of mesangial cells? What is the purpose of these functions?
- Contractile→ contain actin and myosin, can alter capillary surface area available for filtration
- Phagocytic/macrophage function→ingest and remove circulating immune complexes and debris
How do the mesangial cells have access to the circulating immune complexes?
There is no basement membrane across the area where the capillary loop abuts the mesangium; the mesangium is only separated from the circulation by the endothelial cells which have large fenestrae.
What is located between adjacent podocyte foot processes arranged along the GBM? What is its function?
slit diaphragms are between adjacent foot processes. Because they are negatively charged, this is the major place where albumin is restricted from getting into the urinary space
Almost every kidney disease that is associated with heavy proteinuria has either acquired or congenital problems with what structure?
visceral epithelial cell foot processes
What are the key cells in proteinuric conditions? Mutations in what proteins cause congenital nephrotic syndrome?
podocytes;
mutations resulting in defective podocin or nephrin
What structures does the juxtaglomerular apparatus consist of? Where is the JGM apparatus located?
aff and eff arterioles and macula densa; located at the very end of the cortical thick ascending limb of L of H as it comes back to its own glomerulus
What does the macula densa sense?
delivery of how much fluid is reaching the MD
Everything prior to the MD is built for what?
bulk reabsorption
How much total fluid is reabsorbed in a nephron? What percentage is reabsorbed before it reaches the MD?
178 L reabsorbed and 90% of that is reabsorbed before reaching the MD
What are the distal nephron segments built from? Why is this important?
the distal segments are built for fine-tuning; this enables them to create precise homeostasis
In general, what is tubular glomerular feedback (TGF)?
the anatomical way for each nephron to monitor delivery of filtrate to the distal nephron, with each tubule feeding back to its glomerulus, creating a mechanism thru which every nephron can regulate its nephron filtration rate
What happens if it sense too much delivery, which would overload the nephron?
Local mediators are released that change the vascular tone in the afferent arteriole, which then changes the filtration rate by changing the glomerular capillary pressure
What are the starling forces? Which ones promote filtration out of the capillary, and which ones oppose filtration out of the capillary?
A. Promoting filtration out the capillary:
1. Hydrostatic pressure w/in the capillary
2. Oncotic pressure w/in the interstitium
B. Opposing filtration out of the capillary
1. Oncotic pressure w/in the capillary
2. Hydrostatic pressure w/in the interstitium
What determines the net flow in or out of a capillary?
Net sum of the Starling forces and the filtration coefficient Kf (based on how permeable the capillary is)
Which body capillaries are the most permeable? Why? What does this design them for?
Glomerular capillaries because:
1. They are perfused at higher pressures than any other systemic capillaries
2. have an enormous surface area
Thus, they are designed to have huge amounts of filtration
What is the equation for GFR?
GFR=LpS(ΔP-Δtau)
Lp=capillary wall permeability
S=glomerular capillary surface area available for filtration
ΔP=hydrostatic pressure gradient between capillary and bowmans space
Δtau=oncotic pressure gradient between capillary and bowmans space
Why is ΔP always high thruout the length of the glomerular capillary?
Hydrostatic pressure in BS is kept very low.
When you make filtrate, the tubule starts reabsorbing it, so tubular pressure remains very low.
What is the main thing that will determine GFR? How is GFR made?
high glomerular capillary pressure; GFR is made by keeping pressure in glomerular capillary high and normal
What keeps the oncotic pressure in Bowmans space very low?
bc albumin was prevented from entering the urinary space
What is unique about the glomerular vasculature?
there are resistance vessels before and after the the glomerular capillary
How can the pressure in the glomerular capillaries be changed?
by changing the resistance in either arterioles
What happens if the afferent arteriole resistance decreases? How does this affect GFR?
Plasma flow to the glomerular capillaries increases and there is greater transmission of the arterial pressure to the glomerular capillaries.
This change in the glomerular capillary pressure results in increased GFR.
In contrast, what happens to the GFR if you constrict the afferent arteriole?
Constriction of aff arteriole→increased resistance→less RBF→less pressure in the glomerular capillary→reduced GFR
What happens to the GFR when the efferent arteriole is vasodilated?
Vasodil of eff arteriole→reduced resistance→more renal blood flow in eff arteriole→drop in GFR due to lower glomerular capillary pressure
How does vasoconstriction of the efferent arteriole affect the GFR?
Vasoconstriction of efferent arteriole→more resistance→less RBF in the eff arteriole→ increased GFR by increasing glomerular capillary pressure
How is the GFR kept constant over a wide range MA pressures (changes in renal perfusion pressure)?
GFR is kept constant over a wide range of BPs by autoregulation which changes the resistance of the arterioles
How does the autoregulation of GFR respond to Low BP associated with mild to moderate hypovolemia?
Vasodilate aff arteriole and/or vasoconstrict eff arteriole to keep the capillary pressure high→maintain GFR even though there’s low cardiac output (CO) and arterial pressure
Why is urine flow rate/volume not a good indicator of kidney function?
B/c urine flow rate/volume is not autoregulated, so urinary output itself does not mean normal urinary function. Urine flow rate only indicates how much solute and water empty out of the bladder
How is urine flow rate/volume affected by increased perfusion pressure? Does that tell us anything about GFR?
Increased perfusion pressure→increased UF rate (due to pressure natriuresis): as more Na+ is excreted, more water is excreted but that does not mean that GFR changed.
What is the best index of overall kidney function?
GFR
What does the Filtered Load (FL) respresent?
Filtered load represents the amount of substance in plasma that is filtered at the glomerulus per unit time; how much of a substance in plasma in filtered at the glomerular capillary wall
How is FL calculated?
FL (mg/min)= P[x] x GFR
P[x] is the plasma concentration of substance x
What does the Excretion Rate represent?
Excr Rate represents the amount of the substance excreted in the urine per unit time
How is excretion rate calculated? Is urine flow rate autoregulated? So, what happens to UFR when perfusion pressure is increased?
Excr Rate (mg/min)= U[x] x V V is the urine flow rate, and it is not autoregulated. Increased perfusion pressure results in increased V (UFR).
What are the properties of substance that would be a good marker of GFR?
- Present in the plasma at a constant concentration
- Not plasma-protein bound
- Freely iltered, not reabsorbed, secreted, synthesized, or metabolized→ total excretion occurs (FL=excretion rate)
What are the best compounds that meets all the requirements of a good marker of GFR? What is the problem with using these to determine the GFR?
Exogenous: Inulin and the radioisotope Iothalamate.
They are exogenous so they have to be injected IV’ly which is cumbersome and expensive
What is the best endogenous marker of GFR? Why is it not as good as inulin?
Creatinine; not as perfect because 10% is secreted so it over-estimates GFR
What is the equation for GFR using inulin as the marker?
B/c FL(in)=Excr Rate(in):
GFR(ml/min)= (U[in] x V)/P[in]
What does renal clearance represent? What are the units of renal clearance?
It represents the VOLUME of plasma cleared of the substance via elimination per unit time;
units: ml/min
How is the renal clearance of a given substance calculated?
Cl of substance X= (U[X] x V)/P[X] (ml/min)= UV/P
What is used to estimate GFR?
Creatinine Clearance is approximately equal to GFR
What is the Clearance Ratio? What is the equation to calculate clearance ratio?
Defined as the clearance of a particular substance (Cx) divided by GFR:
Cl Ration= Cx/GFR
What do you know about a substance if its Clearance Ratio=1.0?
Then the solute is handled just like inulin and it’s filtered but neither reabsorbed nor secreted, so its renal clearance is equal to GFR
What if a solute’s Clearance Ratio<1? Example?
Then this solute is filtered, but reabsorbed; Sodium
What if a solute’s Clearance Ratio>1? Example?
Then the solute is filtered, and it is actively secreted from the peritubular capillaries into the tubular fluid; Potassium, Hydrogen ion
What if a solute’s Clearance Ratio=0? Examples?
Then either the solute is to large to be filtered (protein), is highly protein bound (certain medications), or it filtered and 100% reabsorbed (Glucose and Amino Acids)
Is there an endogenous substance that can be used to estimate renal plasma flow (RPF)?
No
What exogenous substance is used to estimate RPF? What are the characteristics of this substance that make it a good marker for RPF?
Para-aminohippurate (PAH); it’s an exogenous substance that is filtered and actively secreted such that it is almost completely extracted from the plasma in one pass thru the kidney: Therefore, the Clearance of PAH=RPF
