Renal - Intro to Renal Physiology Flashcards
Define
Internal Sea
Salty ECF
How is the internal sea of land vertebrates maintained?
By controlling the quanity of H2O and Plasma Constituents
Kidney Function
When there is a surplus of H2O or ions in ECF kidneys…
Kidneys eliminate in urine
Kidney Function
When there is a deficit of H2O or ions in ECF kidneys…
Kidneys limit losses until more is ingested
H2O or ions are stored/held onto until more is ingested (not in urine)
What are the main functions of the kidney?
Eliminate waste/toxins (endogenous and exogenous)
Regulation of Water and Electrolyte Balances
Regulation of Erthrocyte Production
Regulation of 1,25-Dihydroxyvitamin D3 (calcitriol) production
Regulation of Acid-Base Balance
A WET BED
Acid-base balance, Water removal, Erthropoiesis, Toxin removal, Blood pressure control, Electrolyte balance, Vitamin D activation
Kidney Function
Electrolyte balance
What does it control and why?
Control of ECF osmolarity essential for maintenance of cell volume
Control of ECF volume key to long-term regulation of BP
Kidney Function
Erthropoiesis
Kindey secretes erythropoietin which stimulates the production of RBCs in bone marrow
Not enough erythropoietin can cause anemia
Kidney Function
Vitamin D activation
Increasing VD in intestines, increases reabsorption of plasma calcium and PO4^3-
1,25-Dihydroxyvitamin D3 (calcitriol)
Calcitrol is the final product of VD -> when not enough calcium is obtained from bones
Kidney Function
Acid-Base Balance
Kidney has a pivotal role: distribuances can be completely corrected thru changes in H+ secretion and HCO3- reabsorption and production
Pathway
Urine
- Kidneys form urine
- Ureters carry urine to bladder
- bladder stores urine
- urine is preiodically emptied through urethra
Define
Nephron
Functional unit of kidney
2 components: vascular/tubular
1.2 million nephrons/kidney
Renal Blood Supply
Renal blood flow is _ by humoral factors
autoregulated
Pathway
Renal Blood Supply
How does blood flow through the renal system?
- Afferent Arterioles
- Glomerular Capillaries (Glomerulus)
- Efferent Arterioles
- Peritublar Capillaries
- Vase recta (sometimes)
- renal vein
Renal Blood Supply
Afferent Arterioles
What do they do/where do they go?
Brings blood to the glomerular capillaries
1/kidney
Blood “Arrives”
Major area of blood flow control
Renal Blood Supply
Glomerulus
What are they? What do they do?
Glomerular Capillaries
Small tuft of capillaries sandwhiched between two arterioles
Filters blood from Afferent Arterioles and drains remaining to Efferent Arterioles
Renal Blood Supply
Efferent Arertioles
What do they do/where do they go?
Drains blood from the glomerular capillaries
blood not filtered by glomerulus “exits” to peritubular capillaries
Renal Blood Supply
Peritubular Capillaries
What are they/where do they go?
A second bed of capillaries that lie after the efferent arterioles and surround the cortical regions of the nephron
Returns blood from the efferent arterioles to the renal vein
Renal Blood Supply
Vasa Recta
What do they do/where do they go?
Specialized capillaries that dip into the renal medulla and surround the loop of Henle
The help maintain the concentration gradient and return fluid to renal vein
Continuation of the Efferent Arteriole in the medulla
Not every peritubular capillary leads to a vasa recta
General Overview
Vascular Component of Nephron
Afferent Arteriole
Glomerulus
Efferent Arteriole
Peritubular Capillaries
General Overview
Tubular Component of Nephron
Bowman’s Capsule
Proximal Tubule
Loop of Henle
Distal tubule
Collecting duct
General Overview
Combined Vascular/Tubular component of Nephron
Juxtaglomerular Apparatus
General Overview of Nephron Functions
Afferent Arteriole
Generally Define Function
Carries blood to the glomerulus
General Overview of Nephron Function
Glomerulus
Generally Define Function
A tuft of capillaries that filters a protein-free plasma into the tubular component
General Overview of Nephron Function
Efferent Arteriole
Generally Define Function
Carries blood from the glomerulus
General Overview of Nephron Function
Peritubular Capillaries
Generally Define Function
Supply the renal tissue
Involved in exchanges with the fluid in the tubular lumen
General Overview of Nephron Function
Juxtaglomerular Apparatus
Generally Define Function/Structure
Produces substances involved in the control of kidney function
Fluid proceeds to distal tubule
Specialized combo of tubular and vascular cells
Important in regulating blood pressue and GFR
General Overview of Nephron Function
Bowman’s Capsule
Generally Define Function
Collects the glomerular filtrate
Double walled cup like invagination
Increases surface area for diffusion
General Overview of Nephron Function
Proximal Tubule
Generally Define Function
uncontrolled reabsorption and secretion of selected substances occur here
Major site of reabsorption
Close to glomerulus
General Overview of Nephron Function
Loop of Henle
Generally Define Function
Establishes an osmotic gradient in the renal medulla that is important in the kidney’s ability to produce urine of varying concentration
Has an ascending and descending limb
General Overview of Nephron Function
Distal Tubule
Generally Define Function
Variable, controlled reabsorption of Na+ and H2O and secretion of K+ and H+ occur here
General Overview of Nephron Function
Collecting Duct
Generally Define Function
Variable controlled reabsorption of Na+ and H2O and secretion K+and H+ occur here
Fluid leaving the collecting duct is urine which enters the renal pelvis
Urine leaves for excretion
What are the two types of nephrons?
Cortical Nephrons
Juxtamedullary Nephrons
How are coritcal and juxtamedullary nephrons distinguished?
By their location and length of their structures
Define
Cortical Nephrons
Location, Structure, Function
Located mostly in cortex; extend just into outer medulla
Short loop of Henle
Surrounded by peritubular capillaries (continuation of EA, in the cortex)
Reabsorption and Secretion
Define
Juxtamedullary Nephrons
Location, Structure, Function
Extend deep into medulla
Long loop of Henle
Efferent arterioles form peritubular caps and vasa recta (continuation of EA, in the medulla)
Reabsorption, Secretion, Concentrate/dilute urine
Both types of nephrons are involved in…
Functions
Secretion and Reabsorption
Only the juxtamedullary nephron involves…
Functions
Concentration and dilution of urine
3 processes involved in urine formation
Glomerular Filtration
Tubular Reabsorption
Tubular Secretion
Define
Glomerular Filtration
What is it? Where does it go?
Pressure (primarily BP) leads to a seperation thru a semipermeable membrane
Found in Glomerulus -> fluid that is filtered into bowman’s capsule
Doesn’t contain cells or protein
“Pushing a portion of plasma onto a conveyor belt” (indiscriminate)
Cells and protein move through glomerulus to bowman’s capsule
Passive
Define
Tubular Reabsorption
What is it? Where does it go?
Fluid filtered into bowman’s capsule/Tubular Lumen is reabsorped into peritubular capillary
Selective
Moves substances back into blood flow
Unwanted substances remain in urine (Filtrate)
Define
Tubular Secretion
What is it? Where does it go?
Selectively adding substances from blood to filtrate
Mechanism for more rapidly eliminating selective substances
Peritubular Capillaries to Tubular Lumen
2nd chance for body to get rid of in urine
Ways substances can be filtered or rebasorbed
The substance is freely filtered and not reabsorped
What happens to the substance?
Substance ends up in urine
Filtration only
EX: Inulin
Ways substances are filtered and reabsorbed
The substance is freely filtered and partly reabsorbed
What happens to the substance?
Filtration, partial reabsorption
EX: Na+, K+, H2O
Ways substances are filtered and reabsorped
The substance is freely filtered and entirely reabsorbed
Substances you don’t want to lose
Filtration, Complete Reabsorption
EX: Glucose and Amino Acids
Ways substanes can be filtered and reabsorped
The substance is freely filtered and entirely secreted
Rarest; None returns to blood
Filtration, Secretion
Ex: Para-aminohippurate, PAH
Glomerular Filtration Barrier
3 layers of the Glomerular Filtration Barrier
Glomerular Capillary Wall (Endothelium)
Basement Mebrane
Inner Layer of Bowman’s Capsule (Epithelium)
Glomerular FIltration Barrier
Glomerular Capillary Wall
Structure, Function
Perforated by many Ig pores
100x more permeable than caps elsewhere in the body
endothelium has “-“ charge
Glomerular FIltration Barrier
What is the purpose of the negative charge on the Glomerular Capillary Wall and Basement Membrane?
Helps prevent negatively charged substances from getting through into the filtrate
Like proteins
Glomerular FIltration Barrier
Basement Membrane
Structure
Acellular gelatinous layer
composed of collagen and glycoproteins
Negatively Charged
Glomerular Filtration Barrier
Inner Layer of Bowman’s Capsule
Function/Structure
Filtration slits between the podocyte processes that encircle the capillaries
Filtration slit diaphragm is composed of podocyn
Glomerular FIltration Barrier
What is freely filtered through the Glomerular FIltration Barrier?
Water
Electrolytes
Molecules - MW less than 5,200
Small ions and molecules
Glomerular FIltration Barrier
What is variably filtered through the Glomerular FIltration Barrier?
Molecules, including up to MW of ~68,000 - 69,000 depending on: Size, Shape, Charge
Long cylindrical filters better than spherical
Mid sized molecules
Glomerular FIltration Barrier
What is not filtered through the Glomerular FIltration Barrier?
Larger Proteins
Golmerular Filtration
What forces are involved in (drive) filtration across the glomerulus?
Starling Forces
Major force is Glomerular Capillary Hydrostatic Blood Pressure
Drives filtrate into Bowman’s Capsule
Golmerular Filtration
What does Glomerular Capillary BP (Pg) depend on?
Arterial pressure
Afferent arteriole resistance
Efferent arteriole resistance
Golmerular Filtration
Why do the afferent and efferent arteriole have a large effect on Glomerular Capillaries?
Why do the GC have a larger pressue than the the peritubular capillaries
Glomerular capillaries are located between the AA and EA, which results in them having a much higher pressure than the peritubular capillaries
Golmerular Filtration
Why is a high glomerular pressure necessary?
To drive glomerular filtration
Golmerular Filtration
Why is it necessary for peritubular capillaries to have a lower pressure?
To permit reabsorption of fluid from the renal interstitium
Golmerular Filtration
Plasma-Colloid Pressure
Define
Unequal distribution of plasma proteins across the glomerular membrane not in bowman’s capsule
Water returns to the glomerulus
Golmerular Filtration
What type of pressure is exerted by fluid in Bowman’s Capsule?
Define
Fluid in BC exerts a hydrostatic pressure
Golmerular Filtration
What is the filtration force in Golmerular Filtration?
Golmerular Capillary Blood Pressure
Golmerular Filtration
What are the opposing filtration forces in Golmerular Filtration?
Plasma-Colloid Osmotic Pressure + Bowman’s Capsule Hydrostatic Pressure
Golmerular Filtration
A postive net filtration favors….
Filtration
Golmerular Filtration
A negative net filtration favors…
Reabsorption
Golmerular Filtration
What is the difference between net filtration along the glomerular capillaries vs. most capillaries in the body?
There is net filtration along the entire length of the glomerular capillaries
The opposing forces are still increasing but always less than Pgc
Oncotic pressure continues increasing along the capillary due to remaining proteins as everything else filters out
What effect do changes in resistance of AA or EA have on blood flow? Why?
The have the same effect because they are in series
Effect of changes in resistance on Renal Blood Flow (RBF) and GFR
At baseline, when resistance is the same in AA and EA…
In general, what happens to pressure
Pressure in GC = 60
AA and EA resistance = 1
Pressure in Peritubular Capillary = 20
Effect of changes in resistance on Renal Blood Flow (RBF) and GFR
When the AA is constricted and the EA is not, what happens to GFR and RBF?
GFR and RBF both decrease
Pressure in GC = 40
AA resistance = 1.5
EA resistance = 1
Pressure in Peritubular Capillary = 13
Effect of changes in resistance on Renal Blood Flow (RBF) and GFR
When the EA is constricted and the AA is not, what happens to GFR and RBF?
GFR increases and RBF decreases
Pressure in GC = 70
AA resistance = 1
EA resistance = 1.5
Pressure in Peritubular Capillary = 10
Effect of changes in resistance on Renal Blood Flow (RBF) and GFR
When the AA is dilated and the EA is not, what happens to GFR and RBF?
GFR and RBF both increase
Pressure in GC = 70
AA resistance = 0.5
EA resistance = 1
Pressure in Peritubular Capillary = 30
Effect of changes in resistance on Renal Blood Flow (RBF) and GFR
When the EA is dilated and the AA is not, what happens to GFR and RBF?
GFR decreases and RBF increases
Pressure in GC = 50
AA resistance = 1
EA resistance = 0.5
Pressure in Peritubular Capillary = 30
Effect of changes in resistance on Renal Blood Flow (RBF) and GFR
Hydrostatic pressure in the glomerulus is controlled by….
Relative tone of afferent and efferent arterioles
Define
Glomerular Filtration Rate (GFR)
The rate at which plasma is filtered (ml/min)
Index of Kidney Function
What does GFR depend on?
Net filtration pressure
Surface area available for filtration
Membrane permeability
GFR = Kf x net filtration pressure
Kf = Surface area + membrane permeabiity
What is the purpose of GFR?
What does it tell us?
GFR is an index of kidney function
Decrease in GFR can mean kidney disease
Increase GFR = Kidney recovery
What is the advatange of a high GFR?
Rapid control of body fluid volume and composition
What is used to measure GFR in clincial research? Why?
Inulin
It is the gold standard for measuring GFR
Inulin is the exogenous marker
What is used to measure GFR in a patient? Why?
Creatinine
It is more convenient than inulin
Endogenous marker
How is GFR measured?
We use the renal clearance of a substance that is freely filtered at the glomerulus, has a stable plasma concentration, is not reabsorbed, secreted, or metabolized by the kidney
Measured exogenously by inulin and endogenously by creatinine
GFR
Inulin
Why is it the gold standard?
Filtered in the glomerulus, no tubular transport
But technically challenging and expensive
GFR
Creatinine
What is it? Why is it used?
Derived from the skeletal muscle creatine
production proportional to muscle mass and is constant
plasma concentration is stable unless there are changes in production (decrease in malnutrition, increase in rhabdomyolysis), or changes in excretion (decreased in acute kidney injury)
Not gold standard because a small amount is secreted
The amount of creatinine excreted per min =
amount of creatinine filtered per minute
What is the relationship between GFR and plasma creatinine?
They are inversely related
Increasing GFR -> decreases creatinine
Neurohumoral Control of GFR
What effects do the sympathetic nervous system have on GFR control?
Decreases RBF, Decreases GFR
Changes blood flow to kidneys
α1 activation -> vasoconstricton -> decreases BF -> decreases GFR
β1 activation -> renin release
vasoconstriction of afferent than efferent
Neurohumoral Control of GFR
What effects does Angiotensin II have on GFR?
Decreases RBF, maintains GFR
Potent vasoconstrictor produced in response to descreases in AA pressure
AA and EA both constrict, EA more so
The larger constriction of EA allows GFR to be maintained
Neurohumoral Control of GFR
What effects do Prostaglandins have on GFR?
Increase RBF, Increase GFR
PGE2 and PGI2 cause dilation of arterioles -> increases RBF, GFR
Effects afferent moreso than Efferent
Maintains GFR and RBF as we age due to increased production
Equation
Blood flow through any organ is represented by…
Q = ΔP/R -> RBF = (Renal artery pressure - renal vein pressure)/ Renal vascular resistance (AA and EA)
Q = Blood Flow
ΔP = MAP - MVP
R = Resistance
Kidneys regulate their BF by _ in response to changes in _.
Adjusting Resistance
Arterial Pressure
Regulating GFR
What are the three ways GFR is regulated by changing RBF?
Autoregulation
Hormonal (Ang II, Prostaglandins)
SNS
Regulation of GFR: Autoregulation
Autoregulation
What is its purpose? How does it work?
Feedback mechanisms intrinsic to the kidney
Operates to keep GFR steady over a wide range of blood pressure
Maintains BF over the range of 80-180
Regulation of GFR: Autoregulation
What are the two types of autoregulation?
Both regulate AA tone
Myogenic Response
Tubuloglomerular Feedback
Regulation of GFR: Autoregulation Mechanisms
Myogenic Response
Define
Fast-acting constriction/dilation to Δ in arterial pressure
Initiated in muscle
When AA is stretched (increase in wall tension), smooth muscle contracts
Pressure sensitive mechanism
Stretch of blood vessels allows Ca from ECF to enter cells and cause contraction
50% autoregulatory response
Regulation of GFR: Autoregulation Mechanisms
Tubuloglomerular Feedback
Define
Complicated signals that respond to Δ in tubular fluid flow rate
Increase GFR -> Increase NaCl in filtrate/Juxtaglomerular apparatus -> Increase AA resistance -> decrease GFR
Flow dependent - Changes BF depending on Flow Rate through the nephrons
Regulation of GFR: Autoregulation
What is the relationship between Arterial BP and GFR?
Arterial BP drives Glomerular Capillary pressure and thus GFR
Increase arterial BP -> increases GFR
Regulation of GFR: Autoregulation
Where is the Juxtaglomerular Apparatus located?
Where the tubule passes through the fork of AA and EA at the glomerulus
What is the structure of the JGA?
What makes it up?
Granular Cells
Extraglomerular Mesangial Cells
Macula Densa
Juxtaglomerular Apparatus
Granular Cells
What are they? What do they?
Modified small muscle cells
Mechanoreceptors of the AA
Make, store, and secrete Renin
Juxtaglomerular Apparatus
Extraglomerular mesangial cells
What are they? What do they?
Holds capillaries together
Full of actin for contraction
contraction closes portion of filtering capillaries -> decreases SA -> decreases GFR
Juxtaglomerular Apparatus
Macula Densa
What is it? What does it do?
Chemoreceptors that detect NaCl
In contact with mesangial and granular cells
NaCl is proportional to rate of filtrate flow
Increase NaCl means Increase GFR -> AA constricts
Decrease NaCl means decrease GFR -> AA dilation
What happens to GFR when NaCl increases?
During high flow rate
Increases in NaCl causes vasoconstriction and increases in GFR
↑ NaCl -> ATP -> Adenosine -> ↑ Ca -> contraction -> ↓ renin
What happens to GFR when there is Low flow rate?
↓Arterial Pressure → ↓Glomerular Hydrostatic Pressure → ↓GFR → ↓Macula Densa/NaCl → ↑ Renin → ↑ Ang II → ↑EA resistance → inhibits ↓Glomerular Hydrostatic Pressure → ↑GFR
↓Arterial Pressure → ↓Glomerular Hydrostatic Pressure → ↓GFR → ↓Macula Densa/NaCl → ↓ AA resistance → inhibits ↓Glomerular Hydrostatic Pressure → ↑GFR
3 most important points concerning Autoregulation
Autoregulation is absent when…
Arterial BP is < 80 mmHg
3 most important points concerning Autoregulation
Despite autoregulation, the RBF and GFR can be changed by…
General
Certain hormones and changes in sympathetic nerve activity
3 most important points concerning Autoregulation
Autoregulation of GFR and RBF provides an effective means for…which ensures…
Autoregulation of GFR and RBF provides an effective means for uncoupling renal function from arterial pressure thus ensuring fluid and solute excretion remain constant
GFR
What can override renal autoregulation?
Sympathetic Nervous System
Extrinsic Sympathetic Control on GFR
Strong activation of renal sympathetic nerves can _ renal arterioles and _ RBF and GFR
Strong activation of renal sympathetic nerves can constrict renal arterioles and ↓ RBF and GFR
Extrinsic Sympathetic Control on GFR
What effect does SNS have on renin and overall GFR?
↑ Renin → RAA →↑Na+ reabsorption (PT)
What would happen to GFR during a hemorrhage?
Hemorrhage →↓ECF Volume → ↓MAP → ↑SNS activation → ↓GFR
↓MAP - detected by carotid baroreceptors
↑SNS activation - Input to Afferent Arteriole (constriction)
Why would GFR need to be decreased?
Decrease GFR to hold onto important things
Pathway of fluid flow
What is the sequence of fluid flow through the kidneys?
General Overview
Kidney → Renal Pelvis → Ureter → Bladder → Urethra
Pathway of fluid flow
What is the sequence of fluid flow through the arterial portion of the renal system?
Renal Artery → Afferent Arteriole → Glomerulus → Efferent Arteriole → Peritubular Capillaries → Renal Vein
Pathway of fluid flow
What is the sequence of fluid flow through the filtrate pathway of the renal system?
Glomerulus → Bowman’s Capsule → Proximal Tubule → Loop of Henle → Distal Tubule → Collecting Duct
Which of the following would cause the greatest decrease in GFR in a person with otherwise normal kidneys?
A. Decrease in renal pressure from 100 to 80 mmHg in normal kidney
B. 50% increase in glomerular capillary filtration coefficient
C. 5 mmHg increase in glomerular capillary blood pressure
D. 50% decrease in afferent arteriolar resistance
E. 50% decrease in efferent arteriolar resistance
F. 5 mmHg decrease in Bowman’s Capsule pressure
E. 50% decrease in efferent arteriolar resistance
Vasodilation of EA → ↓ GFR
Would GFR increase or decrease if there is…
A rise in Bowman’s Capsule pressure resulting from ureteral obstruction by a kidney stone
decrease
Would GFR increase or decrease if there is…
A fall in plasma protein resulting from loss of these proteins from a large burned surface
Increase
Would GFR increase or decrease if there is…
A dramatic fall in arterial blood pressure following severe hemorhage (<80 mmHg)
Decrease
Would GFR increase or decrease if there is…
Afferent Arteriolar vasoconstriction
Decrease
Would GFR increase or decrease if there is…
Tubuloglomerular feedback response to a decrease in tubular flow rate
Increase
Would GFR increase or decrease if there is…
Myogenic response of an afferent arteriole stretched as a result of an increased driving BP
Decrease
Would GFR increase or decrease if there is…
Sympathetic activity to the afferent arterioles
Decrease
Would GFR increase or decrease if there is…
Contraction of the mesangial cells
Decrease
Would GFR increase or decrease if there is…
Contraction of the podocytes
Decrease
