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Nephron
Functional unit of the kidney, with 1-1.5 million nephrons per kidney
divided into cortical and juxtamedullary
Cortical Nephrons
-85% of the nephrons
-located within the kidney cortex
-responsible for waste product removal
-nutrient reabsorption.
Juxtamedullary Nephrons
-Responsible for urine concentration
-longer loops of henle
Renal Functions
Include blood flow, glomerular filtration, tubular reabsorption, and tubular secretion.
What is the pathway of blood flow in the kidney?
Renal artery --> afferent arteriole --> glomerulus --> efferent arteriole --> peritubular capillaries and vasa recta --> renal vein
What is the first vessel that carries blood into the kidney?
Renal artery
Renal Plasma Flow
the amount of plasma that passes through the kidneys in one minute
600-700 mL/min
Where does glomerular filtration occur?
glomerulus which is in the bowman's capsule
What is the approximate nonselective filtration size in glomerular filtration?
<70,000 daltons
What factors influence glomerular filtration?
Cellular structure, hydrostatic and oncotic pressure, and the renin-angiotensin-aldosterone system (RAAS)
Glomerulus
A coil of 8 capillary lobes
in Bowman's capsule
What are the three layers of the glomerulus?
1) Capillary wall with fenestrated endothelium, 2) Basement membrane, 3) Bowman's capsule(innermost layer)
What is the inner layer of Bowman's capsule composed of?
Podocytes and filtration slits
What is the primary protein associated with renal disease?
Albumin
Why is albumin negatively charged in the glomerulus?
Due to the shield of negativity
What is the Shield of Negativity?
A barrier that repels molecules with a positive charge.
How does the Shield of Negativity work?
It repels molecules with a positive charge, even if they are small enough to pass through the three layers of the barrier.
Glomerular Pressure
Regulated by the juxtaglomerular apparatus to maintain consistent glomerular blood pressure
Low systemic blood pressure
-larger afferent and smaller efferent
-prevents decreased glomerular blood flow
High systemic blood pressure
-smaller afferent arteriole
-prevents overfiltration and glomerular damage
Renin
An enzyme secreted by the juxtaglomerular cells when blood pressure decreases
Renin-Angiotensin-Aldosterone System (RAAS)
- regulates blood flow to and within the glomerulus
- responds to blood pressure and plasma sodium changes
juxtaglomerular apparatus
macula densa + juxtaglomerular cells
Macula densa
Controls the efferent arteriole
Juxtaglomerular cells
controls the afferent arteriole
secrete renin
RAAS Process
-Renin is released by kidneys in response to decreased blood volume
-causes angiotensinogen to split & produce angiotensin I
-lungs convert angiotensin I to angiotensin II
-angiotensin II stimulates adrenal gland to release aldosterone
Result of RAAS
-stimulates water and sodium in proximal convoluted tubules
-triggers release of aldosterone
-riggers release of antidiuretic hormone (ADH)
Normal Glomerular Filtration Rate
120-125 ml/min
What is tubular reabsorption?
Process of removing substances from glomerular filtrate and returning them to the blood.
Where does tubular reabsorption start?
Tubular reabsorption starts when the plasma ultrafiltrate enters the proximal convoluted tubule.
What are the 2 types of tubular reabsorption?
active and passive transport
active transport
Energy-requiring process that moves material across a cell membrane against a concentration difference
Active transport of glucose and amino acids takes place where?
proximal convoluted tubule
Active transport of chloride takes place where?
resorbed in the ascending loop of henle
Active transport of sodium takes place where?
resorbed in the distal convoluted tubule
passive transport
movement of molecules across a membrane as a result of differences in their concentration gradients
Where is water NOT reabsorbed?
ascending loop of henle
Urochrome
yellow pigment in urine
renal threshold
plasma level causing active transport to stop
maximal capacity
Glucose threshold
160-180 mg/dL
tubular concentration
1)descending loop of henle-- passive reabsorption of water
2)ascending loop of henle--chloride actively reabsorbed & sodium passively reabsorbed
3)countercurrent mechanism--maintains concentration in the medulla
4)aldosterone--controlled Na reabsorption if needed by body
final filtrate concentration
-Water reabsorption controlled by ADH in response to body hydration
-Osmotic gradient in the medulla
-Vasopressin
ADH
antidiuretic hormone (vasopressin)
when amount of water decreases
increase body hydration
decrease ADH, increase urine volume
decrease body hydration
increase ADH, decrease urine volume
tubular secretion
selectively moves substances from blood to filtrate in renal tubules and collecting ducts
2 major functions of tubular secretion?
1. elimination of waste products not filtered by the glomerulus
2. Regulation of the acid-base balance in the body through secretion of hydrogen ions in the form of NH4 and H2PO4
acid-base balance
the equilibrium in the body between acid and base concentrations
What is normal blood pH?
between 7.35 and 7.45
clearance test
standard test used to measure the filtering capacity of the glomeruli (GFR)
What are the primary substances used in a clearance test?
1) creatine
2) beta 2 microglobin
3) cystatin C
4) radioisotopes
endogenous procedure
substance is already present in the body
-method of choice
exogenous procedure
a test that requires a substance to be infused into the body
Creatine Clearance Test
test done to measure the total amount of creatinine excreted in the urine
creatine
waste product of muscle metabolism
Clearance formula
C = U x V / P
urine conc. x urine flow / plasma conc.
normal values for clearance
Men: 107-139 mL/min
female: 87-107 mL/min
Estimated GFR (eGFR)
based on results of serum creatinine, cystatin C, or B2M values
What does MDRD stand for?
Modification of Diet in Renal Disease
What is the purpose of MDRD?
To identify patients at risk for complications from kidney disease
What variables are included in MDRD?
Race, age, and gender
Beta-2-microglobulin (B2M)
-small protein
-rapidly removed from plasma by the kidney
-used to identify end-shape renal disease and early rejection of kidney transplant
Cystatin C
a small protein produced by nucleated cells which is filtered by glomerulus, reabsorbed and broken down by the renal tubule cells thus decreasing plasma levels
tubular reabsorption test
This is a test to determine the ability of the tubules to reabsorb the essential salts and water that have been non-selectively filtered by the glomerulus.
what is specific gravity of tubular reabsorption?
1.010
Osmolarity
the concentration of a solution expressed as the total number of solute particles per liter.
-more practical
Osmolality
the concentration of a solution expressed as the total number of solute particles per kilogram.
-weight does not change
-more accurate
Freezing point osmometers
-primary urine method
-measured sample is supercooled to form crystals
What does a vapor pressure osmometer measure?
Dew point (temperature at which water vapor condenses to a liquid)
Why does using a vapor pressure osmometer require careful technique?
Due to microsamples, commonly used for serum samples
lipemic serum
-Affects both instruments (freezing and vapor osmometers)
-Insoluble lipids displace serum water
lactic acid
-elevates reading both instruments
-separate or refrigerate with 20 mins
How does the volatility of a substance affect osmometer results?
Volatile substances can elevate results in freezing point osmometers.
Why would you prefer to use a vapor osmometer instead of a freezing point osmometer for volatile substances?
Using a vapor osmometer prevents the volatile substance from affecting the instrument's readings.
Free water clearance
a test to determine the ability of the kidney to respond to the state of body hydration
P-aminohippuric acid (PAH) clearance
test most commonly associated with tubular secretion and renal blood flow
metabolic acidosis
a serious condition that occurs when there's too much acid in the body or when the kidneys can't remove enough acid.
Secretion of H+ is done by?
proximal convoluted tubules
Secretion of NH3 is done by?
distal convoluted tubules
ammonia=
total acidity - titratable acidity