Renal Function: glomerular filtration and renal blood flow Flashcards
6 functions of the kidney
- excretion of metabolic waste products (urea, creatinine)
- regulation of acid-base balance (eliminate H, acids/base, conserve bicarb)
- control of arterial pressure
- secretion, metabolism, and excretion of hormones
- excretion of foreign chemicals
- gluconeogenesis
What are 2 markers that are routine on all serum chemistry analyses?
Urea and creatinine
- are metabolic waste products that need to be eliminated
Kidney is responsible for long term maintenance of ____
pH
- H+ is more tightly regulated than anything else in the body
What is the precursor for angiotensin 2?
Renin
Angiotensin 2 functions as a ______
Vasoconstrictor
- helps maintain bp during hypovolemia and reabsorbs Na and H2O to maintain circulating volume
What 2 hormones are critical to calcium homeostasis and maintaining proper bone metabolism and density?
Vitamin D (can only be activated in the kidney) and parathyroid hormone
What organ is responsible for maintaining blood glucose?
Liver, but kidney can convert AA and precursors to glucose during prolong fasting or liver disease
What is the main reservoir of rapidly available high energy phosphate bonds in muscle?
Phosphocreatinine
Creatinine
- Cr production is proportional to muscle mass normally
- may be increased in acute muscle diseases or decreased in chronic muscle wasting
- 1-2% of muscle creatine turns over daily to creatinine
Why is creatinine an accurate estimate of glomerular filtration rate?
Cr is strictly filtered by the glomerulus with little or no secretion or reabsorption by the renal tubules
Renal damage is ____ over the life of the animal
Cumulative, nephrons don’t regenerate
- Serum Cr will increase over time
Does the kidney alter it’s function in response to changes in creatinine?
No, a change in Cr does not cause a change in GFR for compensation
- use serum Cr as an indicator of a changing GFR (as a result of something else)
GFR primarily responds to changes in ____
Sodium
Excessive protein intake leads to ____
Greater urea production and elimination
- could be due to increased intake, or increased body protein catabolism or degradation (seen in starvation)
Must eliminate _____ as urea, or ____ will accumulate
NH2, NH3 (ammonia)
Changes in urea results in _____
Significant changes in water excretion or retention
_____ follows urea!!!
Water
- urea is a potent osmotic particle
In excessive urea production and elimination, GFR will ______ and urine volume will _______
Increase, increase
During dehydration, the kidney will _____
Actively reabsorb urea to retain water or reduce water excretion
____ and ____ are indicators of loss of function
BUN and Cr (are late indicators)
The kidney is the most important organ for getting rid of ____
H+
- H ion concentration is tightly controlled (to the 0.00004 meq/L
What are the 3 mechanisms of H control?
- buffers: act in seconds
- -> proteins to act as temporary H+ sink
- -> weak acid anion: bicarb, phosphate, etc
- respiration: act in minutes
- -> eliminates CO2, leaving water instead of carbonic acid (bicarb loss)
- kidney: slow, but most important
Every time a CO2 is excreted, a ______ ion is lost
Bicarb (1:1 ratio)
Rates at which different substances are excreted in the urine represent sum of 3 different renal processes
- glomerular filtration
- reabsorption of substances from renal tubules into the blood
- secretion of substances from blood into renal tubules
If intake of water/electrolytes exceeds excretion, the amount of that substance in the body will ____
Increase
Urine formation begins with fluid that is virtually free of ____
Protein
- most substances in plasma are freely filtered, so their concentration in the glomerular filtrate in Bowman’s capsule is the same as in the plasma
What happens to a substance that is freely filtered by glomerular capillaries but is neither reabsorbed or secreted?
Excretion of all that is filtered
- excretion rate is equal to the rate at which it was filtered
- is a good estimate of GFR
- example of creatinine
What happens to a substance that is freely filtered but is partly reabsorbed from the tubules back into the blood?
Rate of urinary excretion is less than the rate of filtration at the glomerular capillaries
- typical for electrolytes (Na, Ca, K)
What happens to a substance that is freely filtered at the glomerular capillaries but is not excreted into the urine?
All the filtered substance is reabsorbed from the tubules back into the blood
- amino acids and glucose
What type of substance is freely filtered at the glomerular capillaries and is not reabsorbed, and additional quantities of this substance are secreted from the peritubular capillary blood into the renal tubules?
Organic acids
- allows them to be rapidly cleared from the blod and excreted in olarge amounts in the urine
What percent of cardiac output does the kidney recieve?
20%
Does albumin get filtered thru the glomerular capillaries?
No, due to its negative charge
What is the functional unit of the kidney?
Nephron
- consists of the glomerulus and its capillary tuft and the tubules
What contributes to increased glomerular filtration rate?
High hydrostatic pressure (60 mm Hg) and endothelial cell fenestrations
- allows for 20% of fluid and smaller solutes out of capillary and into Bowman’s capsule
Proximal convoluted tubules
Site of resorption of 65% of filtrate
- high solute and water resorption
- extremely metabolically active (unregulated absorption)
Loop of Henle
Absorbs 25% of renal filtrate
- high water and electrolyte resorption
- distal end passes by original glomerulus
Distal tubule
Water and Na reabsorption
Collecting duct
Site of final and variable water and sodium resorption under control of hormones (aldosterone and ADH)
- K excretion
- only place in the kidney where fine tuning of filtrate occurs (everywhere else reabsorption occurs at a fixed pace)
Past the _____ is where reabsorption is regulated
Macula densa
The kidney has _______ being fed from the same arterial input
2 capillary beds in series
- each bed has its own control valve to control the path of least resistance
- most capillaries return to venous outflow without going thru the inner medulla
The _____ determines whether fluid is filtered to become urine or not
Path of least resistance
The glomerular capillary bed is under ____ pressure, while the peritubular capillary bed is under _____ pressure
Very high; low
What percent of renal blood flow goes to the medulla?
1-2%
Cortical nephrons
Make up 70-75% of nephrons
- located in the cortex with short loops of Henle that do not penetrate far into the medulla
- extensive peritubular capillary network to reabsorb nutrients without concern for regulating bodily fluid composition
Juxtamedullary nephrons
Make up 25-30% of nephrons
- located deep in the renal cortex near the medulla
- have long loop of Henle with tubule and vasculature penetrating deep into the medulla
- inner medulla hypertonic
- counter current flow
- more limited capillary network with a capillary running parallel to the tubule (vasa recta)
- primarily responsible for regulating fluid retention and majory electrolytes
Both nephrons differ in their ability to ______
Regulate reabsorption
- both filter equally well for elimination of waste products
Kidney uses ____ oxygen as the brain per gram
2X
- oxygen consumed by kidneys is related to high rate of active sodium reabsorption by renal tubules
Inner medulla oxygen tension is as low as _______
10 mm Hg
- makes this area highly susceptible to hypoxia
What 2 things determine GFR?
- balance of hydrostatic and colloid osmotic pressures
- capillary filtration coefficient: product of permeability and filtering surface area of the capillaries
Where does the glomerulus receive its blood supply from?
Afferent arteriole of renal circulation
- drains into an efferent arteriole instead of a venule
What is the basic filtration unit of the kidney?
Renal corpuscle
- a glomerulus and its surrounding Bowman’s capsule
What 3 components make up a glomerular capillary membrane?
- endothelium
- basement membrane
- epithelial cells (podocytes)
= filtration barrier
Capillary endothelium
Perforated by fenestrae
- endowed with fixed negative charges that hinder passage of plasma proteins
Basement membrane
Meshwork of collagen and proteoglycan fibrillae
- large spaces allow for movement of water and small solutes
- proteoglycans have strong negative charges which prevent plasma protein filtration
Epithelial cells
Lining of Bowman’s capsule that surrounds the outer surface of the glomerulus
- not continuous
- podocytes encircle the capillaries
- slit pores allow movement of glomerular filtrate
- also have negative charges
Molecular size
- small molecules increase filterability
- large molecules decrease filterability
Ionic charge
- cations increase filterability
- anions decrease filterability
Neutral dextrans are _____ than negatively charged dextrans of equal molecular weight
Filtered more readily
What is the reason for differences in filterability?
Negative charges of BM and podocytes provide means for restricting large, negatively charged molecules
How does albumin end up being filtered during minimal change nephrotic syndrome?
Due to loss of negative charge
- compromised by inflammation, or acid/base imbalance –> if a hydrogen ion is attached to an albumin it can be filtered
When does albuminuria/proteinuria occur?
When more albumin is filtered than can be reabsorbed
____ movement is paralleled by an equivalent _____ movement
Cation; anion
- if small cations (Na, K) become filtered, then small anions (Cl, bicarb) will also become filtered
Net filtration pressure
Sum of hydrostatic and colloid osmotic forces across the glomerular membrane
GFR formula
Filtration coefficient (Kf) x net filtration pressure
Why is colloidal pressure within Bowman’s capsule negligible?
Protein should not be filtered
- only changes in disease states, which could cause fluid to cross the filtration barrier and into Bowman’s capsule
What is the main factor used to control GFR?
Changes in blood pressure within the glomerulus
- accomplished by varying the afferent and efferent arteriolar sphincters
Capillary filtration coefficient
Hydraulic conductivity x surface area
- 400x increased permeability than most other capillary beds
- not under physiologic control
- affected in some disease states
Capillary hydrostatic pressure
Primary means of physiologic regulation of GFR
- under physiologic control
- promotes filtration
Capillary colloidal pressure
Does exert influence normally
- not under physiologic control
- opposes filtration
Bowman’s hydrostatic pressure
Affected in some disease states
- not under physiologic control
- opposes filtration
Bowman’s colloidal pressure
Essentially zero
- not under physiologic control
- affected in some disease states
Changes (decreases) in filtration coefficient result in
Thickening of glomerular basement membrane = thicker diffusion barrier opposing blood flow
- occurs with chronic hypertension, obesity, diabetes mellitus, glomerulonephritis
- leads to impedment of glomerular filtration and retained waste products
What are the 3 factors that influence glomerular hydrostatic pressure?
- arterial pressure
- afferent arteriolar resistance
- efferent arteriolar resistance
What happens if systemic arterial pressure and/or blood flow increases and there are no changes in glomerular resistance?
There will be an increase in blood pressure and/or flow to the glomerular capillary bed = GFR increased
What serves as the primary means for physiologic regulation of GFR?
Changes in glomerular hydrostatic pressure
- controlled by afferent and efferent arterioles
What happens when afferent arterioles are constricted?
Increased resistance leads to decreased renal blood flow, decreased glomerular hydrostatic pressure = decreased GFR
- helpful during emergency situations but will reduce removal of waste products
What happens during vasodilation of afferent arterioles?
Increased glomerular hydrostatic pressure, increased glomerular flow rate, reducing the increase in colloidal pressure = increased GFR
What happens when efferent arterioles are constricted?
Could still reduce renal blood flow, but increases glomerular hydrostatic pressure = increased GFR
- occurs during dehydration or sustained/moderate to heavy exercise
What happens when efferent arteriole constriction is too severe?
Decreased GFR due to increased colloidal pressure
What happens when efferent arterioles are dilated?
Decrease glomerular hydrostatic pressure = decreased GFR
What happens during times of plentiful water supply?
We don’t need the sphincters
- increased arteriolar pressure and blood flow increases GFR = excess water and salt is filtered across the glomerulus
What are 2 factors that influence glomerular colloid osmotic pressure?
- arterial plasma colloid osmotic pressure
- fraction of plasma filtered by glomerular capillaries (filtration fraction)
Where, within the capillary, does blood protein become more concentrated?
At the end of the glomerular capillary by 20% due to loss of fluid
What provides the basis for reabsorption of water from the tubules?
Increased colloidal pressure leaving the glomerulus and entering the capillaries surrounding the tubules
What happens to colloidal pressure during dehydration?
Leads to increased concentration of albumin in the plasma, which retains fluid in the capillary and diminishes urine filtrate
Increases in blood flow with a constant glomerular pressure results in increased GFR due to ______ in colloidal pressure
Moderate increase
- new blood flows in as fast as the amount of fluid that is being filtered out
- leads to decrease in protein concentration in the tubular capillaries = less reabsorption of fluid from renal tubules, resulting in a greater rate of clearance when excess fluid is consumed
Slower blood flow into the glomlerulus with a constant glomerular hydrostatic pressure results in ______ GFR
Decreased
- colloidal pressure holding fluid in matches that of hydrostatic pressure pushing fluid out before the end of the glomerular capillary
- protein concentration and colloidal pressure in the peritubular capillaries are as high as possible = maximal reabsorption of fluid from renal tubules
Goal of renal blood flow control
Maintain constant GFR over a wide range of flow and pressure ranges for waste excretion without excess loss of fluid
What could result from an increase in blood pressure by 25%?
Increase urine output if all other variables remained the same
- transient: exercise, fear, etc
- persistent: hypertension
In hypovolemic states, it is necessary to ______ urine production, and maintain waste excretion
Minimize
What results from strong activation of renal sympathetic nerves?
Constriction of renal arterioles and decrease in renal blood flow and GFR
- plays important role in reducing GFR during severe, acute disturbances
Endothelin
Vasoconstrictor released by damaged vascular endothelial cells of kidneys
- may contribute to hemostasis during disease states
Myogenic mechanism definition
Ability of individual blood vessels to resist stretching during increased arterial pressure
- helps maintain vascular resistance preventing increase in glomerular blood flow with increase in GFR
Myogenic mechanism method
Smooth muscle in renal arteries and arterioles is stretched, Ca channels open allowing Ca in the cell and activation of myosin/actin contractile elements
Angiotensin 2
Constricts efferent arteriole, increasing glomerular hydrostatic pressure preserving GFR while reducing renal blood flow
How are afferent arterioles protected from angiotensin 2?
Due to local production and release of vasodilators (nitric oxide, prostaglandins) which counteract vasoconstrictor effects of angiotensin 2
Increased angiotensin 2 levels ____ glomerular hydrostatic pressure, and ____ renal blood flow
Increase; decrease
- occurs during decreased arterial pressure/volume depletion, which decreases GFR
What cause vasodilation and increased renal blood flow/GFR?
Prostaglandins (PGE2, PGI2) and bradykinin
- oppose vasoconstriction of afferent arterioles, to prevent excessive reductions in GFR and renal blood flow
Prostaglandins
- COX2 dependent
- critical for maintaining renal and medullary blood flow in hypotensive states
- blocked by NSAIDs = reduction in RBF
Endothelial-derived nitric oxide
Released by vascular endothelium, decreases renal vascular resistance
- basal level of NO is required to excrete normal amounts of sodium and water
- drugs that inhibit formation of NO increase renal vascular resistance and decrease GFR and urinary sodium excretion
Juxtaglomerular complex
Consists of macula densa cells in initial portion of distal tubule and juxtaglomerular cells in the afferent and efferent arterioles
Macula densa
Epithelial cells in the distal tubules that come in contact with afferent and efferent arterioles
- contain Golgi bodies, suggesting secretions toward the arterioles
- senses sodium
Is reabsorption in the proximal portions of the tubules fixed?
Yes, is not regulated and occurs at a fixed rate
A decrease in sodium presentation to the macula densa results in
- afferent arteriolar vasodilation
- efferent arteriolar vasoconstriction, increasing glomerular hydrostatic pressure
= increased filtrate and urine production, increased GFR
An increase in sodium presentation to the macula densa results in
An interpretation of a too high GFR, resulting in a flow that is too fast to allow time necessary to conserve essential nutrients that would then be lost into the urine
- GFR needs to be slowed
Juxtaglomerular effect diagram
Drop in bp = drop in GFR –> decrease flow rate allows more time for loop of Henle to absorb more Na –> macula densa senses decreased Na –> MD signals juxtaglomerular cells to release renin –> angiotensin 2 increases GFR —> MD signals afferent arteriole to dilate = increase RBF and oppose drop in GFR
How are amino acids absorbed by the proximal convoluted tubules?
Cotransport carrier that includes sodium
- so, when amino acids are reabosorbed from the filtrate, so is sodium
How is urine volume increased in relation to decreased sodium presentation to the JG apparatus?
Remember: sodium follows amino acid reabsorption from protein degradation –> extra Na absorption leads to less Na presented to MD –> MD thinks GFR is too low, so it increases GFR
- liver is also producing more urea = increased amount of filtered urea in urine –> urea has osmotic effect!! = increase in water filtered due to increase in GFR is held further down in collecting tubules = increase in urine volume
For every glucose reabsorbed, ___ is also reabsorbed
Sodium
During states of dehydration that result in decreased renal blood flow, signals from MD induce _____ dilation
Afferent arteriolar, to preserve glomerular hydrostatic pressure and preserve GFR
When does the autoregulatory mechanism fail?
In states of reduced cardiac output and reduced renal blood flow
- fails as afferent arteriolar vasoconstriction occurs = poor tubular perfusion and hypoxia
