Kidney Pt2- Filtration Flashcards
Renal corpuscles is made of:
glomerular capillaries + Bowman’s capsule
_______ filters blood to produce a large volume (~150-200 L/day) of filtrate that is similar in composition to plasma minus most plasma proteins
Renal corpuscles
glomerular capillaries + Bowman’s capsule, which make up the _____ _______, produce _____L/day of filtrate
150-200 L/day
the nephron processes the filtrate to produce a small volume _______L/day of excreted urine of varying composition
~1.5 L/day
produces 20 - 25% of the cardiac output which flows through the kidneys
Renal Blood Flow (RBF)
is the portion of blood that is filtered. It ranges from 10-25% of renal blood flow.
Filtration Fraction (FF)
at rest RBF is about ____ L/min
1.2
_________ is the rate at which filtrate enters Bowman’s capsule
Glomerular Filtration Rate (GFR)
the glomerular filtration rate for males is about ______.
the glomerular filtration rate for females is about ____.
90 - 140 mL/min
80-125 mL/min
Glomerular Filtration Rate (GFR) equation is:
RBF x (1 – Hct) x FF
RBF = Renal Blood Flow Hct = Hematocrit/100 FF = Filtration Fraction
Clinically GFR is usually estimated from blood _____ values and is sometimes used to adjust the dosage of medications
creatinine
_______is equal to the total of the filtration rates of the functioning
nephrons in the kidney.
GFR
How was GFR measured before?
The urinary or plasma clearance of an ideal filtration marker, such as inulin, iothalamate or iohexol, is the gold
standard for the measurement of GFR
How is GFR measured now
serum levels of endogenous
filtration markers, such as creatinine, have traditionally been used to estimate GFR, along with
urinary measurements in some cases
______ is accepted as the best overall index
of kidney function.
GFR
A clinician or medical laboratory
can estimate GFR from a person’s serum
creatinine level and some or all of the following
variables: (4)
gender, age, weight, and race
In most healthy people, the normal GFR is
___ mL/min/1.73 m2 or higher.
90
Why are GFR estimates adjusted for body
surface area?
Adjustment for body surface
area is necessary when comparing a patient’s
estimated GFR to normal values or to the levels
defining the stages of CKD.
How does age affect GFR?
GFR declines gradually with age, even in people
without kidney disease. However, decreased GFR
in the elderly is an independent predictor of
adverse outcomes, such as death and cardiovascular disease.
_____ clearance exceeds GFR because it
is secreted by the proximal tubule as well as
filtered by the glomerulus. It can be measured from serum creatinine and creatinine
excretion, or estimated from serum creatinine
using estimating equations
Creatinine
What is the CKD-EPI equation?
The CKD-EPI equation was developed in 2009
to estimate GFR from serum creatinine, age, sex,
and race.
What is the currently recommended
method to estimate GFR?
serum creatinine
Two commonly used
equations when estimating GFR is
Modification of Diet in Renal Disease (MDRD) Study equation and
Cockcroft-Gault equation
What factors affect the creatinine assays?
Proteins in the serum, as well as glucose and
ketoacids in high levels (as occurring in diabetic
ketoacidosis), interfere with the alkaline picrate
assay, giving rise to false elevations in serum
What factors affect creatinine secretion?
Some medications inhibit tubular secretion of
creatinine, thereby decreasing creatinine clearance
and increasing serum creatinine without a
change in GFR
medications that affect creatinine secretion are:
- cephalosporin and aminoglycoside antibiotics
- flucytosine
- cisplatin
- cimetidine
- trimethoprim
________ is a break-down product of creatine/creatine phosphate, mainly from muscle, and is usually produced at a fairly constant rate
Creatinine
Creatinine is eliminated by kidney _____, it is slightly secreted but not ______ so serum creatinine levels give a fairly good estimate of GFR
filtration
reabsorbed
Typical reference ranges for serum creatinine are ______mg/dL, for women and ______mg/dL for men.
- 5 to 1.0
0. 7 to 1.2
Creatinine production is related to _____ _____, so a serum creatinine of 1.2mg/dL may indicate normal kidney function in a male body builder, while a serum creatinine of 1.2mg/dL can indicate significant renal disease in an elderly female.
muscle mass
Part of nephron that collects the filtrate produced by filtration of the blood
Bowman’s capsule
the _____ _____ of Bowman’s capsule is continuous with and conducts filtrate to the proximal convoluted tubule
parietal layer
In the glomerulus, the network of glomerular capillaries are covered by the _______ of the _____ _____ of Bowman’s capsule
podocytes
visceral layer
In the glomerulus, fluid is forced from the glomerular capillaries into the lumen of Bowman’s capsule by the ______ blood pressure inside the capillaries
hydrostatic
The renal corpuscles filter ~ _____ liters of blood to produce ~ 180 liters of filtrate per day. Only about ____ liters is excreted as urine, the rest of the filtrate is reabsorbed back into the blood.
1500L
180L (48 gal)
1.5L
Capillary wall consists almost entirely of _______ cells and basement membrane
endothelial
3 types of capillaries
continuous
fenestrated
sinusoidal
______ capillaries contain ______ _____, and do not have fenestrae. they also have lowest prmeability and more pericytes.
Continuous
Have fenestrae (pores that may or may not be covered by membranes, or fenestral diaphragms); Highly permeable
Fenestrated capillaries
Large diameter with large fenestrae and leaky junctions; very highly permeable
Sinusoidal capillaries
The Filtration Membrane has 3 layers:
Endothelial cells (fenestrated) Basement membrane Podocytes of bowman’s capsule
Water and small molecules can easily pass through the filtration membrane but ____ cells and most ____ _____ cannot
blood
plasma proteins
________ in the visceral layer of Bowman’s capsule are packed closely together to form filtration slits which work with the basement membrane to help prevent plasma proteins from entering the filtrate
pedicels (podocytes)
_____ _____ help prevent the filtration slits from enlarging under pressure
Slit diaphragms
The endothelial cell glycocalyx, basement membrane and podocyte slit membrane contain several charged ______ that influence the filtration of charged molecules
glycoproteins
____ and ____ of a molecule determines its filterability
Size and charge
______ interacts with actin in the podocyte cytoskeleton and is essential in formation of normal filtration slits
nephrin
Mutations of nephrin or basement membrane proteins can cause renal pathologies ____ and _____
congenital nephrotic syndrome
proteinuria
heterogenous conditions characterized by structural abnormalities in the glomerular basement membrane (GBM) due to mutations in type IV collagen. Both conditions typically present with hematuria.
Alport syndrome
Nephropathy (thin glomerular basement membrane)
Glomerular Filtration Rate (GFR) and Net filtration Equation
GFR = Kf [(PGC – PBS) – σ(πGC – πBS)]
Kf= Ultrafiltration coefficient PGC= Hydrostatic pressure in glomerular capillary PBS= Hydrostatic pressure in bowman’s space σ= Reflection coefficient for protein πGC= Oncotic pressure in glomerular capillary πBS = Oncotic pressure in bowman’s space
______ filtration is produced by the blood pressure in the glomerular capillaries
Glomerular
______ _____ _____= total pressure that promotes filtration minus opposing forces
Net filtration pressure (NFP)
Forces Producing Filtration, pushing water out of the capillary
Hydrostatic Blood Pressure
Interstitial Osmotic Pressure
Hydrostatic Blood Pressure:
About _____ mmHg at arteriole end of most systemic capillaries
About ____ mmHg at venule end of most systemic capillaries
About _____ mmHg in glomerular capillaries
30-35
13-16
40-70
Interstitial Osmotic Pressure:
About \_\_\_\_ mmHg Filtrate osmotic (oncotic) pressure in Bowman’s capsule is normally considered to be near \_\_\_ mmHg
1-8
0
Forces Opposing Filtration Keeping water in the capillary
Blood Osmotic (oncotic) Pressure Bowman’s capsule Hydrostatic Pressure
Blood Osmotic (oncotic) Pressure:
About ____ mmHg mainly due to serum albumin & other serum proteins
25 - 30
Bowman’s capsule Hydrostatic Pressure:
About ____ mmHg; may be increased by renal obstruction (i.e., kidney stone)
10
The blood osmotic pressure in the afferent arterioles is _____ than the efferent arteriole
higher
What determines filterability?
size and charge
Size of particle:
_____ nm filters easily, water is ~ 0.3 nm)
< ____ kDa proteins filter easily
> ____ kDa proteins do not filter
2 - 4.2
10
100
Charge of particle:
______ is faster & ______ slower
_____ (~70kDa, negatively charged) does not readily cross the filtration membrane
positive
negative
Albumin
Filterability ratio of Water = ___
1
Exogenous carbohydrate polymers that can be produced with different sizes or charge
Dextran
High molecular weight dextrans are sometimes used therapeutically as a “______ ______”
plasma extender
osmotic action helps _______ to hold water in the blood vessels
albumin
_______ charges inhibit filtration
Negative
Filterability = 1, for substances < 2 nm dependent on _______
charge
Filterability of a Polyanionic Dextran if Negative Charges in the filtration barrier are neutralized cause the curve to shift to the _____, which represents increased permeability
right
If GFR too high:
useful substances are lost due to the speed of fluid passage through nephron (diabetes or diuresis)
If GFR too low:
sufficient waste products may not be removed from the body (renal failure)
The Kidneys are able to maintain a fairly constant GFR over a range of systemic blood pressures by ________ regulation of the afferent and efferent arterioles to maintain GCHP
independent
in the absence of external neural and humoral factors, the kidney will maintain GFR and RBF relatively constant in the face of changes in arterial pressure within range of _____mmHg
80-200
Mechanisms to maintain a functional GFR despite changes in systemic arterial BP:
myogenic mechanisms
tubuloglomerular feedback
Changes in blood pressure (BP) or blood flow via this mechanism, cause immediate compensatory responses by the glomerular vasculature
myogenic mechanisms
Changes in BP or tubular fluid flow via this mechanism, cause both local and systemic compensatory responses
tubuloglomerular feedback
tubuloglomerular feedback cause local regulation of the afferent and efferent arterioles to adjust ____ & ____
GCHP
GFR
tubuloglomerular feedback cause systemic effects on BP by _______ ________ & other chemical messengers
Renin-angiotensin- aldosterone system
Myogenic Mechanism:
systemic increase in BP, stretches the wall of the afferent arteriole stimulating smooth muscle contraction which ____ the diameter of the afferent arteriole decreasing _____ _____ and pressure returning the GFR to its previous level in seconds
reduces
glomerular flow
Myogenic Mechanism:
systemic decrease in BP, decreases the tension in wall of the afferent arteriole stimulating smooth muscle _____ which increases the diameter of the afferent arteriole increasing glomerular flow and pressure returning the GFR to its previous level in seconds
relaxation
The ______ cells lining the arteriole may release chemicals that contribute to myogenic mechanism
endothelial
_______ cells are sensitive to pressure and blood flow rate
Endothelial
chemical messengers of endothelial cells:
NO & prostaglandins → _________
Endothelin & others → _________
vasodilation
vasoconstriction
Afferent arteriole and efferent arteriole vascular smooth muscle respond differently to the various chemical messengers produced by
endothelial cells mesangial cells podocytes juxtaglomerular cells neurons and other tissues
_______ arteriole dilation and/or ______ arteriole constriction will increase glomerular capillary hydrostatic pressure and increase GFR
Afferent
efferent
_______ arteriole constriction and/or ______ arteriole dilation will decrease glomerular capillary hydrostatic pressure and decrease GFR
Afferent
efferent
The cells of the _____ ______ are sensitive to the concentration of sodium chloride in the late thick ascending limb. A decrease in sodium chloride concentration initiates a signal from the macula densa that has two effects:
macula densa
1) it decreases resistance to blood flow in the afferent arterioles via vasodilation, which increases glomerular hydrostatic pressure and helps return glomerulus filtration rate (GFR) toward normal
(2) it increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles
which are the major storage sites for renin
juxtaglomerular cells
increase in sodium chloride concentration would result in _______ of afferent arterioles, and reduced paracrine stimulation of juxtaglomerular cells. This demonstrates the macula densa feedback, where compensatory mechanisms act in order to return GFR to normal.
vasoconstriction
Elevated systemic BP raises the GFR so that fluid flows too rapidly through the renal tubule & ____ and ____ are not adequately reabsorbed.
The macula densa detects that difference & releases vasoconstrictors (_____?) from the juxtaglomerular apparatus causing the afferent arterioles to constrict & reduce GFR
Na+, Cl- and water
adenosine
Decreased systemic BP lowers the GFR so that fluid flows too slowly through the renal tubule and _____ ____ is reabsorbed. The juxtaglomerular apparatus detects the decreased tubular flow and releases a vasodilator (______) causing the afferent arterioles to ____ increasing glomerular blood flow, pressure and the GFR
excess water
prostaglandin
dilate
Vasoconstrictor Chemicals
Norepinephrine & Epinephrine: alpha1 receptors Serotonin Thromboxane A2 & other prostaglandins Substance P Endothelin Angiotensin II Vasopressin (Anti-Diuretic Hormone) ATP (P2 receptors) Adenosine (P1A1A receptors) (vasoconstriction in the kidney)
Vasodilator Chemicals
Adenosine (P1A2 receptors)
low O2, ^CO2, ^H+, ^K+
Nitric Oxide (NO)
Bradykinin {via NO}
Acetylcholine {via NO}
Histamine
Prostacyclin & other prostaglandins
Epinephrine &NE: {Beta-2 receptors}
Dopamine (D1 receptors)
Natriuretic Peptides (ANP & BNP)
Vasoactive Intestinal PeptideAdenosine binds to ___ _______ receptors, which activate G proteins
P1 purinergic
ATP binds to ___ ________ receptors
P2 purinergic
Half-life of adenosine is ~_______, taken up by erythrocytes and endothelial cells
1 second
inhibits adenylcyclase which decreases intracellular cAMP (vasoconstriction)
P1A1
stimulates adenylcyclase which increases intracellular cAMP (vasodilation)
P1A2
P1A1 effect on: Heart: Vessels: Bronchi: CNS:
Heart: Slowing of the rhythm
Vessels: Vasoconstriction
Bronchi: constriction
CNS: Sedation
P1A2 effect on: Heart: Vessels: Bronchi: CNS: Platelets: Mast Cells: Intestinal Secretion:
Heart: Negative inotropic effect Vessels: Vasodilation Bronchi: dilation CNS: Stimulant Platelets: Inhibits aggregation Mast Cells: Degranulation Intestinal Secretion: Inhibition
receptors mediate ATP induced vasoconstriction
P2
______ receptors have been cloned in humans
12 P2Y
_______ receptor is the target of the anti-platelet drug clopidogrel
P2Y12
