Renal I Flashcards
What is the main function of the kidney?
maintain constant body fluid volume
maintain constant fluid composition
endocrine organ
acid-base balance
Define: Osmosis
the movement of water across cell membranes
What is the driving force for the movement of water?
the osmotic pressure difference across the cell membrane
Define: Osmotic Pressure
determined solely by the number of solute particles in the solution
Define: Osmolarity
concentration X number of dissociable particles
the ability of a liquid to undergo osmosis
mOsm/L = mmol/L X number of particles/mol
How does liquid flow?
Liquid flows toward the more concentrated compartment
Define: Oncotic Pressure
the osmotic pressure generated by large molecules such as proteins (has symbol π )
Why is oncotic pressure important in the kidneys?
it regulates fluid movement across the glomerulus and peritubular capillaries
How is body fluid organized?
it is compartmentalized in extracellular and intracellular compartments
Body Fluid: Intracellular Compartment
⅔ total body fluid
Body Fluid: Extracellular Compartment
⅓ total
further divided into → plasma (¼) and interstitial compartments (¾)
Body Fluid: Extracellular Compartment: Plasma Compartment
What is regulated in the plasma compartment?
sodium and water
What do the kidneys maintain volume of?
Extracellular fluid and plasma fluid
What would happen if you drank gatorade (isoosmotic)?
Extracellular volume would increase
osmolarity would stay the same
What happens to intracellular fluid if you change extracellular fluid?
intracellular volume will also change
What causes an increase in EC/IC fluid and a decrease in EC/IC osmolarity?
drinking water
What causes an increase in EC fluid and EC/IC osmolarity and a decrease in IC fluid?
drink/injected with hyperosmotic solution → goes immediately to EC and pulls fluid from IC
What causes a decrease in EC/IC fluid and an increase in EC/IC osmolarity?
dehydration
lose volume, water, ions → increase osmolarity
What causes an increase in EC/IC fluid and a larger decrease in osmolarity than drinking water?
being injected with a hypoosmotic saline
How does fluid drain in the kidney?
Cortex → medulla → minor calyces → major calyces → renal pelvis → ureter
What is the functional unit of the kidneys?
nephron
What makes up the nephron?
renal corpuscle
tubule
Define: Renal Corpuscle
glomerulus (glomerular capillaries)
The glomerulus of all nephrons is found in the renal cortex
What are the segments of the Renal Corpuscle (Glomerulus)?
Bowman’s space and Bowman’s capsule
Where do nephrons extend?
some nephrons extend only to the outer region of the renal medulla while others reach far down into the renal medulla
What are the tubular segments the nephron is divided into?
Proximal convoluted tubule
Descending thin limb of Henle’s loop
Ascending thin limb of Henle’s loop
Thick Ascending limb of Henle’s loop
Distal convoluted tubule
Cortical collecting duct
Medullary collecting duct
What is the main function of the nephron?
it elaborates the fluid within them to produce different amounts and composition of urine depending on the individual’s status
Which nephron segments are found in the cortex of the kidney?
Afferent and efferent arterioles
glomerulus
Bowman’s capsule
Proximal Convoluted Tubule
straight portion of proximal tubule
Macula densa
Distal Convoluted Tubule
Connecting Segment
Cortical collecting tubule
Which nephron segments are found in the medulla of the kidney?
Thin descending limb of loop of Henle
Thin ascending limb of loop of Henle
Thick ascending limb of loop of Henle
Medullary collecting tubule
Define: Juxtaglomerular (JG) apparatus
portion of tubule where the late thick ascending limb of Henle’s loop courses between the arterioles
Made up of 2 cell types: granular cells (JG cells) and macula densa cells
Define: Juxtaglomerular Cells (granular cells)
differentiated smooth muscle cells in the walls of arterioles
secrete renin
Define: Macula densa cells
contributes to control of glomerular filtration rate and to the secretion of renin
How is blood supplied to nephrons/the kidneys?
Blood enters each kidney via the renal artery → subdivides into smaller branches till it reaches afferent arterioles → lead to glomeruli → through glomerular capillaries and combine to form efferent arterioles → subdivide into peritubular capillaries → distribute throughout the length of the nephron
What are Vasa recta?
a type of peritubular capillaries which are long and straight and drape (like hair-pin loops) along the lope of Henle
Renal Innervation
afferent and efferent arterioles are richly supplied with sympathetic noradrenergic neurons
noradrenergic neurons act on both afferent and efferent arterioles via α-adrenergic receptors to cause constriction of both sets of arterioles
Define: Filtered Load
mass of material filtered through glomeruli
Define: Reabsorption
process by which material is transported from lumen to peritubular capillaries
Define: Secretion
process by which material is transported from capillaries to lumen
Define: Excretion
process by which material moves through the length of the nephron and is the combination of reabsorption and secretion
filtration - reabsorption + secretion
Define: Filtration
movement of fluid from glomerular capillaries to Bowman space
Define: Glomerular Filtration Rate (GFR)
rate at which material/substances are filtered through the glomerular capillaries
index of kidney function
volume of filtrate formed per unit time
Define: Glomerular Filtration
bulk flow of fluid from glomerular capillaries into Bowman’s capsule
Define: Glomerular filtrate
fluid within Bowman’s capsule normally doesn’t contain cells, essentially protein-free and contains most inorganic ions and low molecular weight organic solutes
Filtered substances go through:
- Fenestrae in the glomerular-capillary endothelial layer
- Basement membrane
- Slit diaphragms between podocyte processes
Physical aspects (of filtrate) that regulate filtration of substances:
Substances Sizes > 70,000 Daltons mwt., is not filtered
Electrical Charge: negatively charged molecules are less filtered
Why are negatively charged molecules less filtered?
the surfaces of the filtration barrier are coated with polyanions which tend to repel negative charges
Physical aspects of glomerulus-endothelial cell barrier that regulate filtration of substances: Permeability
Size of space/fenestra between endothelial cells
Size of spaces between epithelial podocytes of Bowman’s capsule
What is normal GFR?
approximately 180L/day ( 125 mL/min)
What are direct determinants of GFR?
rate of filtration = permeability X surface area X Net filtration pressure (NFP)
Kf = permeability X surface area
GFR = Kf X NFP
Define: Kf
ultrafiltration coefficient
How is permeability determined?
by size of space/fenestra between capillary endothelial cells and size of pores between epithelial podocytes of Bowman’s capsule
How is surface area determined?
by mesangial cell status and number of viable nephrons (lose as you age)
What happens if mesangial cells relax?
surface area increases
Kf increases
What happens if mesangial cells contract?
surface area of glomerular capillaries decreases
Kf decreases
GFR decreases
How is Net Filtration Pressure (NFP) determined?
NFP = (PGC + πBC) - (PBC + πGC)
Define: PGC
glomerular-capillary hydrostatic pressure
Define: πBC
oncotic pressure of fluid in Bowman’s Capsule
taken as zero (negligible) because there is virtually no protein n Bowman’s Capsule
Define: PBC
hydrostatic pressure in Bowman’s Capsule
Define: πGC
oncotic pressure in glomerular-capillary plasma
What is the overall equation for GFR?
GFR = Kf X NFP (PGC - PBC - πGC)
How does filtration of essential protein effect πGC and NFP?
filtration of essential protein free fluid concentrates protein n glomerular capillary increasing πGC and decreasing NFP
Kf: increased glomerular surface area (mesangial cells relax)
increased GFR
PGC: Increased renal arterial pressure, decreased afferent-arteriolar resistance (arteriolar dilation), increased efferent arteriolar resistance (efferent constriction)
Increases GFR
PBC: Increases intratubular pressure (obstruction of tubular or extrarenal urinary system)
Decreases GFR
πGC: increased systemic oncotic pressure, decreased renal plasma flow
Decreased GFR
Renal Blood Flow (RBF)
the flow from the renal artery, interlobular artery, through afferent and efferent arterioles, peritubular capillaries, veins and renal vein
in typical adult approx. = 1.1 L/min
20-25% of CO
Equation for RBF
RBF = (arterial pressure - renal venous pressure) / renal vascular pressure (R)
R = resistance
How is RBF regulated?
mean arterial pressure
contractile stat of renal arterioles
a given change in arteriolar resistance produces the same effect on RBF regardless of whether it occurs in the afferent or efferent arteriole
more constriction = more resistance = decrease in RBF
How does arteriolar caliber affect RBF?
arteriolar caliber affect RBF independent of whether afferent or efferent arteriolar caliber is altered
How does arteriolar caliber affect GFR?
arteriolar caliber affects GFR in a way that depends on whether afferent or efferent arteriolar caliber has been altered
What happens if the afferent arteriole is constricted but the efferent arteriole isnt?
PGC, GFR, and RPF decrease
What happens if the afferent arteriole is relaxed but the efferent arteriole constricted?
PGC, GFR increase
RPF decrease
What are the functions of RBF?
Indirectly determined GFR (decrease in RBF, decrease in GFR)
modifies the rate solute and water reabsorption by the proximal tubule
participates in the concentration (and dilution) of urine
delivers oxygen, nutrients, and hormones to nephron cells; returns CO2 and reabsorbed fluid and solutes to circulation
delivers substrates for excretion in urine
Regulation of GFR: Factors that influence afferent and efferent arteriolar caliber (how constricted)
Renal sympathetic nerves
Renin-angiotensin system
Autoregulation
Prostaglandins
Regulation of GFR: Renal sympathetic Nerves
Arterioles are richly supplied with sympathetic nerves which release norepinephrine
circulating norepinephrine also causes renal vasoconstriction
What effect does renal vasoconstriction have?
renal vasoconstriction causes a large decrease in RBF and small initial increase in PGC
results in NET decrease in NFP and small decrease in GFR
if filtration continues with constricted arterioles over time, PGC decreases and there is a significant decrease in GFR
Why is regulation of GFR important?
- regulates the amount of fluid going into nephron tubules which helps regulate:
- amount of fluid being excreted/reabsorbed
- clearance of specific molecules (e.g. toxins, drugs, certain metabolites)
- these function to help control fluid volume and composition
Regulation of GFR: Renin-Angiotensin System
Renin produced from JG cells converts angiotensinogen to angiotensin II → angiotensin I converted to angiotensin II by action of angiotensin converting enzyme (ACE)
levels of angiotensin II dependent on levels of renin
Angiotensin II
powerful vasoconstrictor → constricts both afferent and efferent (more effective on efferent) → increases PGC
decreases RBF → decreases PGC, increases πGC
decreases Kf by acting on mesangial cells
has greater effect on RBF than GFR
How does angiotensin II effect GFR in normal situations?
Ang II tends to decrease GFR
How does angiotensin II effect GFR in pathological situations?
Ang II tends to maintain GFR
Where is renin produced?
by granular cells in afferent arteriole of the JG apparatus
What controls renin secretion?
Intrarenal baroreceptors
macula densa
renal sympathetic nerves
Ang II (negative feedback inhibition)
Autoregulation of RBF and GFR
myogenic response → similar to one found in vascular smooth muscle beds
tubuloglomerular feedback
mechanism by which the kidneys regulate RBF and GFR in the face of changes in BP → fine tuning of arteries
Autoregulation: Myogenic response
intrinsic property of vascular smooth muscle → tendency to contract when it is stretched
Autoregulation: tubuloglomerular feedback
goal is to maintain a relatively constant GFR in the face of changes to mean arterial pressure
intrinsic mechanism
doesn’t rely on hormones
works if BP is within the “autoregulatory range”
How does tubuloglomerular feedback regulate GFR?
Increases in arterial pressure cause increases in GFR → increases in GFR raises flow through tubules → increased flow increases delivery to the macula densa → increase is detected → adenosine (vasoconstrictor) generated by JGA constricts afferent arteriole → increases resistance, decreases PGC and GFR
Define: Prostaglandins
local metabolites of arachidonic acid which are produced by both renal sympathetic stimulation and Ang II
ensure there isnt too much constriction
What are the 2 major prostaglandins produced in endothelial cells of renal arterioles?
PGI2 (prostacyclin)
PGE2
vasodilatory agents which are particularly important to prevent excessive vasoconstriction during cardiovascular stress
increase sympathetic nervous activity → significant constriction of arterioles
Define: Nitric Oxide
important vasodilator in control of RBF
counteracts Ang II and catecholamines
when blood flow increases → greater shear force acts on endothelial cells → increases production of NO
Define: Dopamine
vasodilator produced by proximal tubule
serves to increase renal blood flow and inhibit renin secretion
