Lecture 1: Intro kidney fxn Flashcards
What are the functions of the kidney?
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
Define balance, explaining why long-term balance at steady state must equal zero for water and electrolytes
Balance = input - output
Must maintain constant ratio of solutes to water = constant plasma osmolality
How does kidney regulate water and electrolyte balance?
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
How do kidneys regulate acid-base balance?
Regulate bicarbonate excretion
Synthesize new bicarbonate
What are metabolic wastes the kidneys excrete?
Urea
Uric acid
Creatinine
Miscellaneous pigments (from heme)
How do kidneys regulate arterial BP?
Maintains BP and effective circulating volume (by regulating extracellular fluid volume) @ level needed to stay in sodium balance
Role in regulation of vascular resistance
What is regulation of RBC production controlled by?
Erythropoietin (stimulates bone marrow to make more)
When is erythropoietin secreted?
Secreted by kidney in response to hypoxic conditions
What is the kidney’s role in vitamin D synthesis?
Converts vitamin D3 into active form = calcitriol
Define homeostasis
Tendency of an organism to maintain a stable internal environment
Distinguish between superficial cortical, midcortical, and juxtamedullary nephrons based on location of glomerulus and length of loop of Henle
Superficial cortical
Surface of cortex
Short-looped
Midcortical
Mid cortex
Juxtamedullary
Bottom of cortex, before medulla
Long-looped
Describe in sequence the vessels through which blood flows when passing from the renal artery to the renal vein
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
Identify an unique feature of the kidney’s vascular bed
Unique:
Renal vasculature includes TWO capillary beds in series
Describe the 3 layers comprising the glomerular filtration barrier
Capillary endothelium
Basement membrane
Epithelial cells of Bowman’s capsule
Describe in sequence the tubular segments of the nephron
Proximal tubule
(Consulted + straight portions)
Loop of Henle
(Ends with tightly packed macula densa)
Distal nephron
(Distal convoluted, connecting tubule, collecting duct)
How do structures differ of epithelial cells in proximal convoluted tubule vs. collecting duct?
Brush border and more Leakey because not as much ‘tight’ tight junctions
What are the segments of the Loop of Henle?
Thin descending limb
Thin ascending limb **
Thick ascending limb
Ends @ macula densa
**only for long-looped nephrons
What is the function of the macula densa?
Monitor solute delivery and flow to distal nephron
What is the juxtaglomerular apparatus comprised of?
Macula densa
Extraglomerular mesangial cells
Granular cells (secrete renin)
What are two forms of feedback provided by having tubule loop back and return to corpuscle?
(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
What are segments of collecting duct?
Cortical collecting duct
Outer medulla
Inner medulla
Where is the “end” of a nephron unit?
Connecting tubule
Collecting ducts are part of urinary tract
What is the function of the renal corpuscle?
Glomerular filtration
What is the function of the tubule?
Modifies composition of tubular fluid (TF) in order to make urine
These modifications involve processes of tubular reabsorption and secretion
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
Compare the filtration of fluid in systemic vs. glomerular capillaries
Glomerular capillaries have higher filtration fraction (FF)
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
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
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
How are solutes transported in glomerular capillaries?
Convective transport!
Solutes dragged across capillary wall by fluid filtering out of capillaries
Define glomerular filtration
Fluid filtered by glomerular capillaries = 20% of RPF
Goes into tubule
Includes:
20% of water
20% of small solutes
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
Define urinary excretion
Elimination of solutes and water in urine
Anything that exits inner medullary CD
Write a general equation that summarizes the kidney’s handling of a substance (“fundamental law of the kidney”)
Excretion =
Filtration + Secretion - Reabsorption
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
List typical normal plasma concentrations of sodium, potassium, chloride and bicarbonate
PNa = 140 mM
PK = 4 mM
PCl = 105 mM
PHCO3 = 24 mM
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
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
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
Write the fundamental law of the kidney for solute X (assume X is freely filtered)
Ux Vdot =
Px * GFR + Sx - Rx
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
What are examples of substances that are filtered but not reabsorbed or secreted?
Inulin
Creatinine (some secretion)
What are examples of substances that are filtered and reabsorbed (but not secreted)?
Na+
Cl-
glucose
Amino acids
What are examples of substances that are filtered and secreted (but not reabsorbed)?
Organic anions
Organic cations
What are examples of substances that are filtered, reabsorbed and secreted with net Rx or Sx?
K+
Urea
Uric acid
What is a modified fundamental law of the kidney for water?
Vdot = GFR - R(H20)
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
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
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
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
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
What is maximum osmolality in medulla determined by?
Length of loop of Henle
% of nephrons with long loops
For ADH, identify its site of synthesis and secretion
Synthesized in hypothalamus
Secreted by posterior pituitary
What is another name for ADH?
Vasopressin
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
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
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
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
For aldosterone, list its site of synthesis and secretion
Secreted by adrenal cortex
For aldosterone, list its major effects on tubular transport
Na+ reabsorption in CNT/CD
Inc. K+ secretion in CNT/CD
Describe two mechanisms for aldosterone regulation
Ang II = inc. aldosterone
Inc. plasma concentration of potassium = inc. aldosterone
For ANP, review the regulation of its secretion
ANP is released from atria by stretch due to increased pressure or volume
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
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
What does PTH do?
Parathyroid hormone regulates excretion of bone minerals
What are regulators of RBF and GFR?
ADH
Ang II
ANP
Sympathetic division
Other mediators = adenosine, PGs, NO
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
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
What does 1 liter of water equivalent to?
1 liter of water = 1 kg of water
What is a typical normal value for Vdot, or V?
1 ml/min or 1.5 L/day
What is the percentage of nephrons with short loops of Henle?
80-90%
What are short-looped and long-looped nephrons called?
All superficial cortical nephrons = short loop
All juxtamedullary nephrons = long-loop
What is the plasma flow filtered into the interstitium in typical capillaries?
< 0.1%
What is the percentage of filtered sodium + anions reabsorbed in the proximal tubule?
60-70%
What is the percentage of filtered sodium + anions reabsorbed in the thick AL of the loop of Henle?
25%
What is the percentage of filtered sodium + anions reabsorbed in the distal convoluted tubule?
4-8%
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
In which segment of the tubule is the main epithelial cell type called the principle cell?
Connecting tubule (CNT) and the collecting duct (CD)
What regions of the tubule are always permeable to water?
PT and thin DL
Which is the most important diluting segment of the tubule?
Thick AL - reabsorbs 25% of filtered sodium + anions and is always impermeable to water
Where is there negligible sodium reabsorption in the tubule?
Thin DL
What is secreted in response to increased atrial stretch?
Atrial natriuretic peptides
What is secreted in response to decreased atrial stretch?
ADH
What increases sodium reabsorption in the PT?
Ang II
Also increases sodium reabsorption in the DCT and CNT/CD
What does increased sodium reabsorption in the proximal tubule lead to ?
Since PT is always permeable to water, increased sodium reabsorption = increased water reabsorption
What decreases sodium reabsorption in the collection duct?
ANP
What inhibits renin secretion?
Ang II and ANP = hormonal renin secretion regulations
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
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
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
