Lecture 1: Intro kidney fxn Flashcards

1
Q

What are the functions of the kidney?

A

Regulation of water + electrolyte balance
Regulation of acid-base balance

Excretion of metabolic waste
Excretion of hormones, drugs, and their metabolites

Regulation of BP
Regulation of RBC production

Synthesis of vitamin D
Gluconeogenesis

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2
Q

Define balance, explaining why long-term balance at steady state must equal zero for water and electrolytes

A

Balance = input - output

Must maintain constant ratio of solutes to water = constant plasma osmolality

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3
Q

How does kidney regulate water and electrolyte balance?

A

Kidney adjusts excretion of water and electrolytes to achieve balance in spite of wide variations in dietary intakes and non-renal losses => maintain constant plasma osmolality, Posm

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4
Q

How do kidneys regulate acid-base balance?

A

Regulate bicarbonate excretion

Synthesize new bicarbonate

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5
Q

What are metabolic wastes the kidneys excrete?

A

Urea

Uric acid

Creatinine

Miscellaneous pigments (from heme)

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6
Q

How do kidneys regulate arterial BP?

A

Maintains BP and effective circulating volume (by regulating extracellular fluid volume) @ level needed to stay in sodium balance

Role in regulation of vascular resistance

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7
Q

What is regulation of RBC production controlled by?

A

Erythropoietin (stimulates bone marrow to make more)

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8
Q

When is erythropoietin secreted?

A

Secreted by kidney in response to hypoxic conditions

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9
Q

What is the kidney’s role in vitamin D synthesis?

A

Converts vitamin D3 into active form = calcitriol

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10
Q

Define homeostasis

A

Tendency of an organism to maintain a stable internal environment

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11
Q

Distinguish between superficial cortical, midcortical, and juxtamedullary nephrons based on location of glomerulus and length of loop of Henle

A

Superficial cortical
Surface of cortex
Short-looped

Midcortical
Mid cortex

Juxtamedullary
Bottom of cortex, before medulla
Long-looped

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12
Q

Describe in sequence the vessels through which blood flows when passing from the renal artery to the renal vein

A

Renal artery
Segmental artery
Interlobular/Arcuate/Interlobular artery

Afferent arterial
(blood to individual nephrons!)

Glomerulus
Efferent arterial
Peritubular capillaries or Vasa Recta
(If cortical / juxtamedullary nephron)

Interlobular, arcuate, interlobular vv.
renal vein

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13
Q

Identify an unique feature of the kidney’s vascular bed

A

Unique:

Renal vasculature includes TWO capillary beds in series

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14
Q

Describe the 3 layers comprising the glomerular filtration barrier

A

Capillary endothelium

Basement membrane

Epithelial cells of Bowman’s capsule

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15
Q

Describe in sequence the tubular segments of the nephron

A

Proximal tubule
(Consulted + straight portions)

Loop of Henle
(Ends with tightly packed macula densa)

Distal nephron
(Distal convoluted, connecting tubule, collecting duct)

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16
Q

How do structures differ of epithelial cells in proximal convoluted tubule vs. collecting duct?

A

Brush border and more Leakey because not as much ‘tight’ tight junctions

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17
Q

What are the segments of the Loop of Henle?

A

Thin descending limb
Thin ascending limb **
Thick ascending limb
Ends @ macula densa

**only for long-looped nephrons

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18
Q

What is the function of the macula densa?

A

Monitor solute delivery and flow to distal nephron

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19
Q

What is the juxtaglomerular apparatus comprised of?

A

Macula densa

Extraglomerular mesangial cells

Granular cells (secrete renin)

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20
Q

What are two forms of feedback provided by having tubule loop back and return to corpuscle?

A

(1) tubuloglomerular feedback
- macula densa cells send signals to afferent arteriole to regulate glomerular filtration and renal blood flow (RBF)

(2) regulation of renin secretion
- macula densa cells send signals to granular cells

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21
Q

What are segments of collecting duct?

A

Cortical collecting duct

Outer medulla

Inner medulla

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22
Q

Where is the “end” of a nephron unit?

A

Connecting tubule

Collecting ducts are part of urinary tract

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23
Q

What is the function of the renal corpuscle?

A

Glomerular filtration

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24
Q

What is the function of the tubule?

A

Modifies composition of tubular fluid (TF) in order to make urine

These modifications involve processes of tubular reabsorption and secretion

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25
Describe in sequence the structures of the urinary tract
From collecting duct, urine drains into Minor calyx Major calyx Renal pelvis Ureter Bladder ``` Internal sphincter (SM) External sphincter (SKM) ``` Urinary excretion
26
Compare the filtration of fluid in systemic vs. glomerular capillaries
Glomerular capillaries have higher filtration fraction (FF)
27
Define and list normal values for renal blood flow (RBF), renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction (FF)
RBF = 1.1 L/min RPF = 600 mL/min GFR = 120-125 ml/min = 180 L/day FF = 20% = GFR/RPF
28
Given the CO and hematocrit in a normal individual, predict: RBF RPF GFR
RBF = CO * 0.2 RPF = (1 - hematocrit) * RBF GFR = 0.2 * RPF
29
What is the ultrafiltrate? What does it include and exclude?
Ultrafiltrate = fluid that filters out of glomerular capillaries Excludes: cellular elements of blood (RBCs) + plasma proteins Includes: small solutes
30
How are solutes transported in glomerular capillaries?
Convective transport! | Solutes dragged across capillary wall by fluid filtering out of capillaries
31
Define glomerular filtration
Fluid filtered by glomerular capillaries = 20% of RPF Goes into tubule Includes: 20% of water 20% of small solutes
32
Define tubular reabsorption and tubular secretion
Remaining 80% travels to efferent arteriole and 2nd capillary bed Tubular reabsorption: From tubule to blood (From 20% that got filtered) Tubular secretion: Blood to tubular fluid
33
Define urinary excretion
Elimination of solutes and water in urine | Anything that exits inner medullary CD
34
Write a general equation that summarizes the kidney's handling of a substance ("fundamental law of the kidney")
Excretion = | Filtration + Secretion - Reabsorption
35
Identify the abbreviations and describe the units that are most commonly used in kidney physiology for ``` plasma concentration of solute X Urine concentration of Solute X Urine flow rate Rate of tubular reabsorption of solute X Rate of tubular secretion of solute X ```
[Plasma] = Px Units: moles, mass, electrical equivalents, osmoles Urine concentration = Ux Units: same as Px Urine flow rate = V dot or V Units: ml/min; L/day Tubular reabsorption = Rx Tubular secretion = Sx Units: mmol/min, mg/min, mEq/day
36
List typical normal plasma concentrations of sodium, potassium, chloride and bicarbonate
PNa = 140 mM PK = 4 mM PCl = 105 mM PHCO3 = 24 mM
37
Define the rate of filtration of solute X and describe its units
Amount of solute filtered per unit time Units: mmol/min, mg/min, mEq/day
38
Write an equation for calculating rate of filtration of (A) freely filtered solute (B) solute that binds to plasma proteins
Freely filtered: Rate of filtration = Px * GFR Bound to plasma proteins: Rate of filtration = fu * Px * GFR Where fu = fraction of solute unbound
39
Define the rate of excretion of solute X, describe its units and write an equation for its calculation
Amount of solute excreted per unit time Units: mmol/min; mg/min; mEq/day Rate of excretion = Ux * Vdot
40
Write the fundamental law of the kidney for solute X (assume X is freely filtered)
Ux Vdot = | Px * GFR + Sx - Rx
41
Write a modified form of fundamental law of the kidney for (A) solute that's filtered but not reabsorbed or secreted (B) solute that's filtered and reabsorbed but not secreted (C) solute that's filtered and secreted but not reabsorbed (D) solute that's filtered, reabsorbed and secreted with net reabsorption (E) solute that's filtered, reabsorbed with net secretion
Filtered: Ux Vdot = Px * GFR Filtered + reabsorbed: Ux Vdot = Px * GFR - Rx Filtered + secreted: Ux Vdot = Px * GFR + Sx Net reabsorption: Ux Vdot = Px * GFR - net Rx Net secretion: Ux Vdot = Px * GFR + net Sx
42
What are examples of substances that are filtered but not reabsorbed or secreted?
Inulin Creatinine (some secretion)
43
What are examples of substances that are filtered and reabsorbed (but not secreted)?
Na+ Cl- glucose Amino acids
44
What are examples of substances that are filtered and secreted (but not reabsorbed)?
Organic anions Organic cations
45
What are examples of substances that are filtered, reabsorbed and secreted with net Rx or Sx?
K+ Urea Uric acid
46
What is a modified fundamental law of the kidney for water?
Vdot = GFR - R(H20)
47
List the major electrolytes, nutrients, and waste products that represent the "cast of characters" for Renal System I
Electrolytes: Na, K, Cl, HCO3 Phosphate, Ca, Mg (bone minerals) Nutrients: Glucose, amino acids Wastes: Creatinine, urea, uric acid
48
Describe the reabsorption of sodium plus anions and water
Proximal tubule: 2/3 Na + anions, water reabsorbed Thick ascending limb: Reabsorbed 1/4 Na + anions, but NO water Distal convoluted tubule: Reabsorbs 4-8% Na + anions, but NO water CNT, CD: Reabsorbs 1-3% Na + anions, water permeability regulated by ADH
49
State the approximate minimum and maximum values of urine osmolality (U osm) - how concentrated - in the normal kidney Briefly explain how it can vary over such a wide range
Varying water reabsorption/ADH = varied U osm ``` U osm (min) = 50 mOsm/kg H2O U osm (max) = 1200 mOsm/kg H2O ```
50
Identify the concentrating and diluting segments
Diluting: Thick ascending limb Distal convoluted tubule CNT, CD in absence of ADH Concentrating: Collecting duct in presence of ADH
51
Define the medullary gradient
In region of medulla, there's a gradient of increasing osmolality Inner part of medulla (tip of papilla) = max concentrated Because of medullary gradient, there is reabsorption of water in thin DL and reabsorption of NaCl in thin AL
52
What is maximum osmolality in medulla determined by?
Length of loop of Henle % of nephrons with long loops
53
For ADH, identify its site of synthesis and secretion
Synthesized in hypothalamus Secreted by posterior pituitary
54
What is another name for ADH?
Vasopressin
55
For ADH, list its major effects on tubular transport
Increases water permeability of CNT and CD (Allows medullary gradient to pull water out of tubular fluid, resulting in increased osmolality of TF or more concentrated urine) Increases urea permeability of inner medullary CD
56
For ADH, briefly describe two mechanisms for regulating its secretion Identify the mechanisms most important in regulation of kidney function
Dec. stretch of arterial BRs or veno-atrial mechanoreceptors = inc. ADH *** Inc. plasma osmolality as sensed by osmo receptors in hypothalamus = inc. ADH Inc. AngII in severe volume depletion can also stimulate inc. ADH secretion
57
For Ang II, briefly describe the direct and indirect mechanisms for its slow pressor effects
Direct Ang II = inc. sodium reabsorption in proximal tubule = inc. water reabsorption Also inc. sodium reabsorption in DCT and CNT/CD Indirect Ang II = inc. aldosterone = inc. Na reabsorption in CNT/CD
58
Review renin secretion regulators
Sympathetic division: Inc. symp. Tone to kidneys = stimulate beta1 R's on granular cells = inc. renin secretion Renal baroreceptors Dec. stretch of afferent arterioles = inc. renin secretion Macula densa: Dec. NaCl delivery = signal to increase renin secretion via adenosine and PG signaling molecules Hormones: Inc. AngII or ANP = dec. renin secretion
59
For aldosterone, list its site of synthesis and secretion
Secreted by adrenal cortex
60
For aldosterone, list its major effects on tubular transport
Na+ reabsorption in CNT/CD Inc. K+ secretion in CNT/CD
61
Describe two mechanisms for aldosterone regulation
Ang II = inc. aldosterone Inc. plasma concentration of potassium = inc. aldosterone
62
For ANP, review the regulation of its secretion
ANP is released from atria by stretch due to increased pressure or volume
63
Describe effects of ANP on tubular transport of sodium
dec. Na+ reabsorption in CD (inc. Na+ excretion) Effects on excretion of sodium are OPPOSITE to Ang II and aldosterone
64
For sympathetic division, briefly describe its general effects on kidney function
Na+ retention, plasma volume expansion Direct mechanism: Inc. Na+ reabs. In PT = inc. water reabsorption Inc. Na+ reabs. In DCT Indirect mechanism: Inc. symp tone to kidneys = inc. renin secretion = inc. Ang II
65
What does PTH do?
Parathyroid hormone regulates excretion of bone minerals
66
What are regulators of RBF and GFR?
ADH Ang II ANP Sympathetic division Other mediators = adenosine, PGs, NO
67
What does 1 mEq equal?
1 mEq = 1 mmol of electrical charge Electrolyte with valence v = v mEq of solute Example: 1 mM CaCl2 = 4 mEq/liter
68
What is 1 mOsm equivalent to?
1 mOsm = 1 mmol of particles 1 mmol of solute that dissociates into n discrete particles in solution = n mOsm of solute Example: 1 mM CaCl2 = 3 mOsm/kg H2O
69
What does 1 liter of water equivalent to?
1 liter of water = 1 kg of water
70
What is a typical normal value for Vdot, or V?
1 ml/min or 1.5 L/day
71
What is the percentage of nephrons with short loops of Henle?
80-90%
72
What are short-looped and long-looped nephrons called?
All superficial cortical nephrons = short loop All juxtamedullary nephrons = long-loop
73
What is the plasma flow filtered into the interstitium in typical capillaries?
< 0.1%
74
What is the percentage of filtered sodium + anions reabsorbed in the proximal tubule?
60-70%
75
What is the percentage of filtered sodium + anions reabsorbed in the thick AL of the loop of Henle?
25%
76
What is the percentage of filtered sodium + anions reabsorbed in the distal convoluted tubule?
4-8%
77
What is the percentage of filtered sodium + anions reabsorbed in the connecting tubule and collecting duct?
1-3% For "fine tuning" to maintain sodium balance
78
In which segment of the tubule is the main epithelial cell type called the principle cell?
Connecting tubule (CNT) and the collecting duct (CD)
79
What regions of the tubule are always permeable to water?
PT and thin DL
80
Which is the most important diluting segment of the tubule?
Thick AL - reabsorbs 25% of filtered sodium + anions and is always impermeable to water
81
Where is there negligible sodium reabsorption in the tubule?
Thin DL
82
What is secreted in response to increased atrial stretch?
Atrial natriuretic peptides
83
What is secreted in response to decreased atrial stretch?
ADH
84
What increases sodium reabsorption in the PT?
Ang II Also increases sodium reabsorption in the DCT and CNT/CD
85
What does increased sodium reabsorption in the proximal tubule lead to ?
Since PT is always permeable to water, increased sodium reabsorption = increased water reabsorption
86
What decreases sodium reabsorption in the collection duct?
ANP
87
What inhibits renin secretion?
Ang II and ANP = hormonal renin secretion regulations
88
How do rates of excretion and filtration relate if substance X is filtered and reabsorbed?
If filtered and reabsorbed (or filtered, reabsorbed and secreted with NET reabsorption!) Rate of excretion < rate of filtration Examples: Na, Cl, glucose, amino acids
89
How do rates of excretion and filtration relate if a substance is filtered and secreted?
If substance X is filtered and secreted (or filtered, reabsorbed and secreted with NET secretion), Rate of excretion > rate of filtration Examples: PAH, Cr
90
How do rates of excretion and filtration relate if substance is filtered and neither reabsorbed nor secreted?
Rate of excretion = rate of filtration Example: inulin