D: Overview Renal & Renal Clearance Flashcards
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A: The Kidneys have 8 Functions:
1) Excrete metabolic waste & foreign substances = This stuff is harmful and has to be excreted JUST AS FAST as its made. Ex: [Protein Urea] / [Nucleic Acid-Uric Acid] / [CreatiNINE] & [Urobilin from Hgb catabolism]
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2) Regulate H20 & electrolyte balance = which can be independently regulated [i.e. low Na+ but High K+ are addressed separately]
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3) Regulate [Extracellular Fluid Volume] using [Renin ENZYME]= IS A CONSEQUENCE OF #2 & ONE OF THE MOST IMPORTANT. Blood Plasma is a big component. This Ensures Vascular space is filled with enough volume for blood to circulate
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4) Maintain [Plasma Osmolality] = Summed up concentration of dissolved solutes is thrown off when inputs/outputs of H20 & [dissolved solutes] are changed disproportionally [i.e. drinking PURE water or salty meal]. KIDNEYS MAINTAIN THIS
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5) RBC Production= Kidneys secrete [Erythropoietin peptide hormone] to stimulate RBC production from Bone Marrow when PaO2 in local environment of secreting cells in [cortical interstitium] DECREASE. FETUS secrete [Erythropoietin peptide hormone] from LIVER.
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6) Regulate [Vascular Resistance]= Kidneys secrete vasoactive substances via [renin-angiotensin pathway] that influence [peripheral vascular resistance] & [systemic arterial BP]
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7) Regulate [Acid-Base balance] = pH has to be regulated within a LIMITED RANGE.
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8) Regulate [Vitamin D Production] = carries out last step of Vit D production & produces [Calcitriol 1,25 dihydroxyvitamin D] for bone ReSORPtion
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B: Kidneys lie on the POSTERIOR abd wall retroperitoneally and are 11 cm long and [115-170 grams]. On the medial side is an indentation that passes the Renal Artery, Vein, Nerves & Pelvis
C: Kidney Anatomy
ºOuter Region= Cortex (sits under The Capsule)
ºinner region = medulla (Divided into [renal pyramids])
**BOTH of these are composed of nephrons, [blood vessels], lymphatics & nerves
*[renal pyramids] are in the medulla. At the Base of pyramids is the corticomedullary border and
**[renal pyramid] Apex terminates in a papilla that lies in the [minor calyx/which collect urine). [minor calyx] expand into 2 or 3 open-ended porches = [MAJOR CALYX]
D: [MAJOR CALYX] feeds the Pelvis , which is the upper expanded part of the ureter. [Calyx, Pelvis and ureter walls] ALL have smooth muscle that contract to push Urine to the Bladder!
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A: There are [1.2 million nephrons] per Kidney which each consist of:
[Renal Corpuscle]—>PCT—> [Loop of Henle] —>[Macula Densa] —> DCT —-> [Cortical COLLECTING DUCT]
- [Renal Corpuscle] consist of Glomerular capillaries and [Bowman’s capsule]
- PCT initially forms several coils followed by straight piece descending toward medulla
- [Loop Henle] is made of the [PCT straight portion]->[descending thin limb]–>[hairpin turn]–>[Ascending thin limb]–>[THICK Ascending limb]
- near the end of the [THICK Ascending limb] the nephron passes by the Afferent & EFFERENT arterioles in a short segment called the [Macula Densa]
- DCT then extends into the Cortex where 2 or more nephrons JOIN —> [Cortical COLLECTING DUCT]
- [Cortical COLLECTING DUCT] is a POST-NEPHRON structure tht reEnters [medulla Outer region] and becomes [Outer Medullary Collecting Duct] —-> [innnner medullary collecting duct]
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A: The [Juxtaglomerular Apparatus] is made of the
º[Macula Densa Thick ASCENDING limb]
º[Extraglomerular mesangial cells]
º[GRANULAR CELLS (makes angiotensin II and renin)] found in [Afferent Arterioles]
and more!
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A2: Filtration barrier =
1st: Endothelial Cell layer
2nd: Basement Membrane of [Podocyte foot process]
3rd: [Podocyte foot process]
B: [Podocytes] surround [Glomerular capillaries] and contain a large nucleus with 3 indentations. Cell processes form interdigitating [foot processes
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B: PCT/[Proximal Convoluted Tubule] =
-HIGH volume reabsorption–> low gradient
-extensively amplified apical membrane = [BRUSH BORDER]
-[Basolateral membrane] is VERY invaginated with MANY Mitochondria for ACTIVE TRANSPORT
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C: [Loop of Henle]=
*Creates high interstitial Osmolality
*Descending/Ascending thin limbs don’t have much of apical or basolateral surface with few mitochondria
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D: DCT=MANY MITOCHONDRIA WITH low volume reabsorption—> HIGH GRADIENT
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E: [Macula Densa of THICK Ascending Limb] is found in JGA and is the SENSOR FOR TUBULAR FLOW.
[THICK Ascending Limb] and DCT HAVE MANY MITOCHONDRIA & extensive invaginations of [Basolateral membrane]
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F: [Collecting Duct (cortical vs. outer medulla vs. inner medulla)] is made of
1. [principal cells] :have moderately invaginated [basolateral membrane], few mitochondria and play big role in [NaCl ReAbsorption] & [K+ secretion]
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All Nephron Cells (EXCEPT [COLLECTING DUCT INTERCALATED CELLS]) have apically targeted cilium protruding into tubule fluid. These are:
- Mechanosensors that detect tubule fluid Flow changes
and - Chemosensors that initiate [Ca+ dependent signaling] –>controls kidney cell function/proliferation/differentiation/Apoptosis!
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RENAL VASCULARIZATION=
1) {RENAL ARTERIES}
A: [Renal BLOOD Flow] = 1200 mL/min and is [25% of Total Cardiac Output]
vs.
B: [renal plasma flow]= 660 ml/min
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2) {GLOMERULAR CAPILLARIES}= These form the [EFFERENT ARTERIOLE] which leads into a 2nd capillary network called the [peritubular capillaries]–>which gives blood to nephron
A: [Glomerular Filtration Rate] = 125 mL/min
B: [Filtration Fraction] = [GFR/ rpf] = 20%
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3) {PERITUBULAR CAPILLARIES}= 2nd capillary netowork that contains 90% of [Renal BLOOD Flow] and ReAbsorbs water & solutes from renal cortex
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4) {VASA RECTA CAPILLARIES}= contain the other 10% of [Renal BLOOD Flow] (8% in Outer Medulla) & (2% in inner medulla) and ReAbsorbs water & solutes from renal MEDULLA
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A: Mesangium = area between [Glomerular capillaries] that contain [mesangial cells] which are surrounded by an extensive extracellular matrix.
B: There are 2 renal blood flow circuits. Renal Arterial blood can pass thru glomerular capillaries and then travel to EITHER the [PERITUBULAR CAPILLARIES] or [vasa recta capillaries] BUT there is very little mixing of the 2 circuits with one another!
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A: We excrete [0.4 - 1.7 mL/min] of URINE!
B: URINE COLOR MATTERS!= color comes mostly from pigment urochrome which is compound of urobilin or urobilinogen
1. Dark Amber on standing= comes from oxidation of urobilinogen
- Dark Amber on Collection = state of Anti-diuresis (Urine Flow is less than 1 mL/min) = UR NOT URINATING OUT MUCH WATER
- ## pale amber on Collection = state of Water Diuresis (Urine Flow is MORE than 1 mL/min) = URINE CONTAINS A LOT OF WATERB: Clearance = Amount of Plasma able to be completely cleared of a specific substance in 1 minute.
B1: Substances Found in Urine have obviously been Cleared Out from the plasma and then urinated Out—> so these substances have [Clearance values] GREATER than 0 mL/min
B2: stuff NOT FOUND IN URINE are being preserved by the body and not cleared out—> have [Clearance values] = 0 mL/min
C: Abnormal concentrations of substances in urine signifies renal or [extra-renal] pathology (i.e. proteinuria /glucoseuria /bacteria in urine)
C2: HCO3 / Glucose / Ketones / Leukocytes / Protein and Bilirubin SHOULD NEVER BE FOUND IN URINE!
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B: [Adrenal CORTEX Aldosterone]—>Kidney RETAINS Na+ from [DCT]
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C: [ATRIAL Natriuretic Peptide]–> Kidney SECRETES Na+ into Urine & it [VasoDILATES afferent glomerular arteriole]
—> INC GFR but also DEC water volume. ANP HAS NO EFFECT ON RBF and is the OPPOSITE of [Aldosterone].
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D: [Parathyroid Hormone] –> Kidney RETAINS Ca+ thru renal tubules
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A: 90% of HTN is [idiopathic essential] but 10% has RENAL INVOLVEMENT
B: In CHF, DEC Circulating Blood Volume/Cardiac Ouput—>DEC perfusion of Kidney—>Kidneys INC Salt/Water ReAbsorption–>INC Blood Volume and EXACERBATES CHF!
C: TOTAL GFR Normally = 125 mL/min but [Single Nephron GFR= 50 nL/min] with 90% Renal Reserve. This means we can live on 33% Renal Function!
D: Tx for [Chronic Renal Failure]=
1) Hemodialysis
2) Artificial Kidneys
3) Renal Transplants (human vs. Xeno vs. stem-cell)
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A: The Nephron is represented by 3 general processes
1) Glomerular filtration
2) ReAbsorption of a substance from tubular fluid BACK into blood
B:In the Kidneys [Load = Concentration x Flow]
so…
1. [Kidney INPUT load] = [Arterial Plasma concentration of substance x] • [arterial Renal Plasma flow]
- ## [KIDNEY OUTPUT LOAD]= {[VENOUS Plasma concentration of substance x] •[venous Renal plasma flow] } + [(Urine concentration of substance x) • (Urine flow rate)]C: Kidney INPUT MUST equal Kidney [OUTPUTS (venous flow vs. urine)] and so this means RPFa will be GREATER THAN RPFv if [Urine flow rate] is more than 0 mL/min. = [Conservation of Mass]
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A: Any substance that is NEITHER synthesized nor metabolized will have amounts that enter the kidney EQUAL to the COMBINED amount leaving Kidney via venous AND Urine
B: There are 4 Basic Renal Loads
1) Filtered Load= Tubular Input #1= [Arterial plasma concentration x GFR]
2) Secreted Load = Tubular Input #2
3) ReAbsorbed Load= tubular OUTPUT
C: Renal Clearance indicates excretory abilities of the Kidneys. It is defined as the AMOUNT of plasma COMPLETELY CLEARED of substance Z within 1 minute. It ONLY DEPENDS on rate substance Z is excreted into URINE and is a FLOW in mL/min. —-> [ (Arterial plasma concentration Z) = (Urine concentration Z) x (Urine flow rate) ]
C2: Clearance is a Virtual Flow. Kidney receives only 25% of [Cardiac Output] (which is RPF) AND only filters 20% of this RPF (which is GFR). Some substances are COMPLETELY cleared from renal blood on a single pass.
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When Deriving CLEARANCE of Plasma substance Z…
A: Load of Z delivered to Kidney = Load of Z REMOVED from Kidney IN URINE—> [(Concentration Z CLEARED) = (Urine Concentration Z) x (Urine flow / Plasma concentration Z) ]
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B: RENAL HANDLING
(Cz = Clearance of Z from plasma)
1. If Cz is less than GFR = Z is filtered AND ReAbsorbed
- If Cz is EQUAL to GFR = Z is Filtered
- ## If Cz is GREATER THAN GFR= FILTERED AND SECRETEDC: Range of Clearance VALUES
*minimum Cz= 0 —> [glucose has Fz>0 and Rz>0] //
[Proteins have Fz= 0 so ARE NOT FILTERED] [Glucose IS filtered BUT EQUALLY ReAbsorbed! ]
**Mid-Range Cz—-> [GFR for inulin and creatiNINE where Fz>0 and Sz = Rz = 0 ] [RPF for PAH & (Organic dyes) where Fz>0 & Sz> 0] <—This is ALWAYS Cleared out of the plasma and is both Filtered AND Secreted!
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B: Advantages of using [Exogenous INULIN]
ºnon-toxic
ºfreely filtered fructose polymer with MW of 5000
ºnot produced nor consumed by Kidneys= Inert
ºEasily measurable in plasma & urine
ºdoes NOT bind to plasma proteins
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C: DISadvantages of using [Exogenous INULIN]
ºEXPENSIVE
ºMUST BE INFUSED TO OBTAIN CONSTANT BLOOD TITERS
D: [Inulin Clearance] = [GFR] = [Urine concentration x (Urine Flow)/(Plasma Concentration)] . Clearnace is measured in mL/min. —> [IC= UC x (UF/PC) = GFR]
