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What are the two types of nephrons?
cortical (85%)
juxtamedullary (15%)
What are cortical nephrons responsible for?
removal of waste products and reabsorption of nutrients
What are juxtamedullary nephrons responsible for?
The concentration of urine
What renal functions control the kidney’s ability to clear waste products and maintain the body’s electrolyte and fluid balance?
renal blood flow
glomerular filtration
tubular reabsorption
tubular secretion
What is the order of blood flow through the renal capillaries?
renal artery, afferent arteriole, glomerulus, efferent arteriole, peritubular capillaries, vasa recta, renal vein
What allows the arterioles to create the hydrostatic pressure differential?
Size of the arterioles, afferent bigger than efferent
What does the hydrostatic pressure differential of the glomerulus maintain?
glomerular filtration
glomerular capillary pressure
renal blood flow
Where does the immediate reabsorption of essential substances take place?
proximal convoluted tubule
Where does the final adjustment to urinary composition take place?
distal convoluted tubule
Where do the major exchanges of water and salt take place?
the loops of Henle
What is the average renal blood flow?
1200 ml/min
What is the average total renal plasma flow?
600 to 700 ml/min
What do normal values for renal blood flow and renal function depend on and must be adjusted for?
Body size
What does the glomerular filtration barrier serve as a non selective filter for?
plasma substances with molecular weights less than 70,000
What other factors influence the actual filtration process of the glomerulus?
cellular structure of the capillary walls and bowmen capsule
hydrostatic pressure
oncotic pressure
RAAS
What is the fenestrated endothelium?
Pores in the glomerular endothelium that increase the capillary permeability but do no allow large molecules or blood through
What is the shield of negativity?
A negative charge on the glomerular barrier that repels negativity charged molecules
What is usually repelled by the shield of negativity?
albumin
What maintains glomerular blood pressure?
Juxtaglomerular apparatus
How does the juxtaglomerular apparatus maintain glomerular blood pressure regardless of systematic blood pressure?
Dilation and constriction of the afferent and efferent arterioles
What does RAAS regulate?
Flow of blood to and within the glomerulus
What does RAAS stand for?
Renin-angiotensin-aldosterone system
What does the RASS respond to?
Changes in blood pressure and plasma sodium content
What happens with low plasma sodium?
Decreases water retention in circulatory system leading to decreased blood volume and low blood pressure
What is renin and when is it secreted?
An enzyme produced by the juxtaglomerular cells and is secreted when the macula densa sense low blood pressure/plasma sodium
What does renin react with?
angiotensinogen
What hormone is made from the reaction of renin and angiotensinogen?
Angiotensin I
How is angiotensin I converted into angiotensin II?
In the alveoli of the lungs through the actions of ACE (angiotensin converting enzyme)
How does angiotensin II correct renal blood flow?
dilates afferent arterioles and constricts efferent arterioles
stimulating reabsorption of sodium and water in the proximal convoluting tubules
triggers release of aldosterone by the adrenal cortex and ADH from the hypothalamus
What does aldosterone do?
Acts on the distal convoluted tubule to reabsorb sodium
What is the difference between renal filtrate and plasma?
Filtrate contains no plasma proteins, protein bound substances and cells
What is the specific gravity of filtrate as it leaves the glomerulus?
1.010
What are the cellular mechanism involved in tubular reabsorption?
active transport
passive transport
What must happen for active transport to occur?
substance to be reabsorbed must combine with a carrier protein
What is active transport used to reabsorb?
glucose, amino acids and salts in the proximal convoluted tubule
chloride in the ascending loop of henle
sodium in the distal convoluted loop
What is passive transport the result of?
The movement of molecules across a membrane as a result of differences in their concentration or electrical potential on opposite sides of the membrane
Where does passive reabsorption of water take place?
All parts of the nephron except the ascending loop of Henle
Where does passive reabsorption of urea take place?
the proximal convoluted tubule and ascending loop of Henle
Where does the passive reabsorption of sodium take place and what is it accompanied by?
the ascending loop of henle and it accompanies the active transport of chloride
Like passive transport, what can active transport also be influenced by?
Concentration of a substance
How does concentration affect active transport?
When the concentration of a substance is abnormally high it exceeds the maximal resorptive capacity and the substance begins to appear in the urine
What is the renal threshold?
The plasma concentration as which active transport stops
What is the renal threshold for glucose?
160-180 mg/dl
Where does renal concentration begin?
the descending and ascending loops of Henle
What is in the renal medulla that helps with concentration?
A high osmotic gradient
What is the selective reabsorption process in the loops of henle called?
countercurrent mechanism
Where is water reabsorbed and where is sodium and chloride reabsorbed in the loop of henle?
water is reabsorbed in the descending and sodium in the ascending loops
What prevents excessive reabsorption of water as the filtrate passes through the highly concetrated medulla?
The impermeability of the ascending loop to water
What does the countercurrent mechanism help to maintain?
the osmotic gradient of the medulla
Where does the final concentration of filtrate begin?
Starts in the late distal convoluted tubule and continues in the collecting duct
What does reabsorption of water in the collecting duct depend on?
the osmotic gradient in the medulla and the hormone vasopressin(ADH)
What cause the release of ADH by the posterior pituitary gland?
A decrease in the amount of water in the body
What does ADH act on?
the walls of the distal convoluted tubule and the collecting duct
What does a high level of ADH do?
Increases the permeability of the collecting duct and distal tubule to water
What happens to ADH levels and urine volume when the body is dehydrated?
ADH levels increase and urine volume decreases
What does tubular secretion involve?
passage of substances from the blood in the peritubular capillaries to the tubular filtrate
What two major functions does tubular secretion serve?
elimination of waste products not filtered by the glomerulus
regulating the acid-base balance in the body through the secretion of hydrogen ions
What does the buffering capacity of blood depend on?
Bicarbonate ions that are filtered by the glomerulus and must be returned to the blood
What prevents the excretion of bicarbonate in the filtrate?
The secretion of hydrogen ions by renal tubular cells, mostly in the proximal convoluted tubule
What are the two primary methods of hydrogen ion excretion?
combining with filtered phosphate instead of bicarbonate
by combining with ammonia
What can the distal convoluted tubule and collecting duct to if there is an additional need to eliminate hydrogen ions?
produce ammonium ions
What can a disruption of the secretory functions of kidneys result in?
metabolic acidosis or renal tubular acidosis
What are the standard tests used to measure the filtering capacity of the golmeruli?
Clearance test
What do clearance tests measure?
The rate in mL/min which kidneys are able to remove a filterable substance from the blood
To ensure accurate measurement of the GFR the substance being used must?
Be neither secreted nor reabsorbed by the tubules
What substances are used in clearance tests?
creatinine
beta2-microglobulin (B2M)
radioisotopes
What is an exogenous procedure?
A test that requires an infused substance
What is an endogenous procedure?
When the test substance is already present in the body
What is creatinine?
A waste product of muscle metabolism
Why is creatinine often used to measure glomerular function?
It is normally found in relatively constant levels in the blood
What are some disadvanatages of using creatinine?
some is secreted to tubules as blood levels rise
medication can inhibit secretion of creatinine causing falsely low serum levels
bacteria can break it down if stored improperly
meat heavy diets can raise creatinine levels
not reliable for those suffering from muscle-wasting diseases or performing heavy exercise
must be corrected for body surface area
What is the greatest source of error in clearance procedures?
improperly times urine specimens
What is the standard formula for milliliters of plasma cleared in a minute?
C=(UV)/P
Do estimated glomerular filtration rates (eGFR) require a timed urine specimen?
No
What is cystatin C?
A small protein produced by all nucleated cells
Why is cystatin C used to measure GFR?
It is filtered, reabsorbed and broken down by the renal tubular cells so serum concentration can be used to directly measure GFR
What is beta2-microglobulin?
A protein that found on human leukocyte antigens that regularly dissociates from the cells
What is B2M used for?
To distinguish kidney disorders as either glomerular or tubular
How does the concentration of B2M distinguish between different disorders of the kidney?
If serum levels are normal but urine levels increased than a tubular disorder is indicated.
If serum levels are increased but urine levels remain low than a glomeruli disorder is indicated
Where does the value of a GFR test lie?
In the determination of the extent of nephron damage in renal disease, to monitor the effectiveness of treatment to prevent further damage and to determine the feasibility of administering medication
GFR is determined by both the?
number of functioning nephrons
the functional capacity of those nephrons
What is used to determine the functionality of the tubules?
concertation tests
What is urine concertation largely determined by?
Hydration levels
What does a urine-to-serum ratio or a urine osmolality indicate?
Normal tubular reabsorption
What does osmolality measure?
the number of particles in a solution
What does specific gravity measure?
Both the number and density of the particles in a solution
Why is osmolality more accurate for evaluation of renal concentrating ability?
Renal concentration involves small particles so larger particles such as glucose and urea do not contribute
What makes the conversion from temperature to milliosmoles in freezing point osmometers?
The fact that 1 mol of a nonionizing substance dissolved in 1kg of water lowers the freezing point
What is the dew point?
Temperature water vapor condenses to a liquid
What do solutes do to the vapor pressure?
Decrease it
What factors influence osmolarity?
lipemic serum (displacement of water by insoluble lipids)
lactic acid
volatile substances (do not effect vapor pressure but do effect freezing point)
What are the major clinical uses of osmolarity ?
evaluating renal concentrating ability
monitoring renal disease
monitoring fluid and electrolyte therapy
differential diagnosis of hyper and hyp-natremia
evaluating the secretion and renal response to ADH
Why are reference values for urine osmolality hard to establish?
Because of factors like fluid intake and exercise that can influence urine concertation
What is free water clearance?
A test used to determine the ability of the kidney to respond to the state of body hydration
How is free water clearance calculated?
By first determining the osmolar clearance and subtracting the urine volume
What is the equation for osmolar clearance?
Cosm= (Uosm x V)/ P osm
What does the osmolar clearance indicate?
How much water must be cleared each minute to produce a urine with the same osmolality as the plasma
What test is most commonly associated with tubular secretion and renal blood flow?
p-aminohippuric acid (PAH) test
What is the criteria to measure blood flow?
Substance must be removed from the blood primarily in the peritubular capillaries rather than the by the glomerulus
What does the ability of kidneys to produce an acid urine depend on?
the tubular secretion of hydrogen ions as well as the production and secretion of ammonia by the distal convoluted tubule