Renal anatomy, filtration and blood flow Flashcards
What % of cardiac output does the kidney get?
22%
What is the GFR
125ml/min
What 2 types of nephrons are there
Cortical
Juxtamedullary
What is in the renal corpuscule
Bowmans capsule
Glomerulus
what type of cells are in the PCT
Cuboidal cells with microvilli
What cells are in the loop of Henle
Thin segmented cells to assist water absorption
What cells are in the collecting tubule
Intercalated cells
Principle cells
What type of cell structure do you find in the DCT
Regular cuboidal cells
What is the purpose of a podocyte
- Podocytes secrete and maintain the basement membrane
- The pedicels interdigitate —> loss of this or effacement is what contirbutes to minimal change disease and cause proteinuria
- The gap between these is known as slit diaphragms or slit pores
How does perfusion pressure affect GFR??
What % of CO is renal blood flow? How much of this is actually needed for metabolic supply?
20% of cardiac output
This is 10x what is needed
How does medullary blood flow compare to cortical blood flow
10x in cortex
How is renal blood flow regulated? Which areas of the kidney have the capacity to regulate and which do not?
- Myogenic autoregulation via Afferent and efferent arteriole resisatnce changes - especially afferent arteriole
- Tubuloglomerular feedback
MAP 75-70 GFR is regulated as constant
Juxtamedullary nephrons do not have self regulation
Explain tubuloglomerular feedback
2 elements
- Change in afferent tone
- Alteration in renin secretion
Macula densa (ascending LOH/earlyDCT) detects changing tubular flow rate via sodium flux causing cellylar swelling. As basolateral membrane has contact with arterioles or extrraglomerular mesangial cells local feedback
Reduced GFR = reduced flow –> reduced adenosine release and prompting NO release and renin release with afferent limb dilation
Increased flow –> increased perfusion pressure –> adnosine release –> reduces GFR
Describe the subdivisions of the renal artery
- Renal artery / interlobar artery / arcuate artery / interlobular artery / afferent artery / efferent artery
What renal blood flow grossly going to be controlled by (Ohns law)
- RBF = (MAP – CVP) / RVR
- MAP ~100mmHg
- CVP ~2mmHg
What does decreased glomeular filtration lead to as part of tubuloglomerular feedback
↓ Filtration results in reflex afferent arteriolar relaxation
What 3 mechanisms regulated renal blood flow intrinsically
RAAS (hormonal)
Myogenic autoregulation
Tubuloglomerular feedback
Neuronal control of renal blood flow occurs how?
Sympthetic nerves causing vasoconstriction via alpha mechanism
Afferent AND efferent constriction
Efferent > afferent. i.e. GFR is preserved MORE than renal blood flow
What effect does SNS have on GFR
Overall slight reduction in GFR
Efferent > afferent constriction
Increased capillary hydrostatic pressure
Reduced filtered load of Na though
Also triggers renin seccretion
Directly triggers Na/H exchange in PCT
Where is renin released from
Granular cells from juxtaglomerular apparatus
Triggers for renin release
Beta 1 stimulation directly from SNS
Macula densa secondary to reduced Na content in DCT
Reduced perfusion/hypotension
Angiotensin 2 effects 5
- Direct vasoconstriction of peripheral vasculature
- Afferent > efferent vasoconstriction reducing renal blood flow markedly more than SNS
- Mesangial cell constriction reducing surface area for filtration
- Increased ADH/aldosterone secretion
- Thirst
- Increased Na reabsorption
What vasodilates in the afferent arterioles
ANP (dilates afferent, constricts efferent)
PGE2 and PGI2
NO
Normal renal blood flow
1.1L/min
Normal plasma blood flow
600ml/min
Filtration fraction
20%
Filtrate is?
Plasma - oplasma proteins/plasma bound substances
How much is filtered per day in the kidney
172L
Urinary output at baseline
1ml/kg/hr
1ml/min
GFR equation
net filtration pressure x filtration coefficient
Average capillary net filtration pressure
17mmHg
What is glomerular hydrostatic pressure
55-60mmHg
What is capsular hydrostatic pressure
16mmHg
What is blood colloid osmotic pressure
30mmHg
What is bowmans capsule oncotic pressure
0
What affects the hydrostatic pressure in Bowmans capsule
MAP
Catecholamine
Local autoregulation - myogenic, tubuloglomerular feedback, hormones (AT2 and PGE2)
How does osmotic pressure change along the capillary in bowmans capsule
Increases with filtration as protein free fluid is filtered a higher proportion of protein remains
What is filtered
Water
Electrolytes
Glucose
Small amount of uncharged molecules
What separates tubular content from blood flow in the nephron
single layer of epithelial cells and a basement membrane
What is the main purpose of a cortical nephron
Filtration
What is the main purpose of a juxtamedullary nephron
concentration
What is Kf? What dose it depend on?
Glomemrular filtration
Permeability and surface area
What factors contribute to the filtration membrane
- Capillary endothelium
- Basemment membrane negatively charged
- Foot processes
What size molecule can not be filtered
> 7000 Daltons
What 3 cells are part of the juxtaglomerular apparatus
- JG cells of the afferent arterioles/granular cells
- Macula densa
- Mesangial cells
What constricts the afferent arteriole
Catecholamine and SNS
2. Adenosine via tubuloglomerular feedback
3. Endothelin 1
What factors increased efferent arterioles constriction
ANP
SNS and catecholamines
AT2
What happens to renal blood flow, GFR and filtration fraction with afferent constriction
What happens to renal blood flow, GFR and filtration fraction with afferent dilation
What happens to renal blood flow, GFR and filtration fraction with efferent dilation
What happens to renal blood flow, GFR and filtration fraction with efferent constriction
Clearance =
The VOLUME of a drug cleared per unit of time
urine concentration x urine volume / plasma concentration
Urine concentration x urine volume / plasma concentration =
renal clearance
How can you calculate GFR
- Inulin clearance
- Creatinine clearance
What propoerties favour calculation of GFR using clearance
- Freely filtered
- Not reabsorbed
- Not secreted
What is inulin
Natural polysacchardie
How do you use inulin to measure GFR
Continuous infusion of the natural polysacchardie and constant plasma concentration –> where clearance = infusion volume
Creatinine is?
A byproduct of muscle metabolism
What factors make creatinine a good marker for GFR measurement? What makes it a poor one?
Relatively cnostantly produced
Not metabolised
Free filtered
Not reabsorbed
Does have some secretion which relatively becomes more important with reducing GFR (overestimates GFR when low)
Problems
- Variation in race, muscle mass, age, sex and diet
- Can only use it when production and clearance are in steady state
What is the eqaution for direct measurement fo creatinine clearance
Urine concentration x volume / plasma concentration
Therefore 24 hour creatinine urine collection must be done
What estimates of GFR are instead used
Creatinine clearance via Cockroft Gault equation
◦ Cockcroft Gault formula (0.83 correlation with creatinine clearance) ‣ Clearance = (140-age) x weight x sex (1 for male, 0.85 for female)/72 x creatinine in micromol/L
What is the Cockroft Gault equation
◦ Cockcroft Gault formula (0.83 correlation with creatinine clearance)
‣ Clearance = (140-age) x weight x sex (1 for male, 0.85 for female)/72 x creatinine in micromol/L
What are 2 alternative creatinine clearance calculations other than Cockroft Gault
CKD EPI
MDRF
What are the flaws in estimating creatinine clearance based on plasma creatinine
Rely on stable Cr measurements less reliable in critically ill
Less reliable with low GFR overestimating it
Inaccuracy with large muscle mass, older age, malignancy, diet
What is a normal GFR value
- GFR 90-120 ml/min/1.73m^2 or 125ml/min
What are the factors determining GFR
◦ GFR = filtration coefficient x (Glomerular capillary pressure - bowman’s capsule hydrostatic pressure) - reflection coefficient for blood protein x (glomerular capillary oncotic pressure - bowman’s capsule oncotic pressure)
How big is the afferent to efferent pressure drop passing through the glomerulus
2mmHg form 60 –> 58
What 3 factors will determine renal afferent arterial flow
CO
Renal blood flow
Local vasoconstriction
What is the hydrostatic pressure in Bowmans capsule
15mmHg
What happens to oncotic pressure along the capillary? Why? What values
Increases
‣ Increases along the capillary, as protein free-fluid is filtered leaving a higher concentration of protein within the capillary. This change in capillary oncotic pressure is proportional to the filtration fraction - a greater filtration fraction will cause a higher oncotic pressure of fluid in the capillary.
‣ Dependent on plasma protein concentration - increased concentration increases oncotic pressure, dropping GFR
‣ Oncotic pressure at afferent end ~21mmHg, and 33mmHg by the efferent end
‣ As protein is not filtered in normal states, the oncotic pressure in Bowman’s Space is usually assumed to be 0mmHg
What is capillary oncotic pressure in Bowmans capsule
21mmHg –> 33mmHg
What is the net filtration pressure in the glomerulus
24mmHg at afferent, 17mmHG mean, 10mmHg at efferent
What is the filtration coeffiicent of the kids determined by?
Surface area and membrane permeability
Surface area is dependent on?
Gloemrular mesangial contraction
Age and number of gloemruli
Glomerular membrane is composed of what factors> What is not filtered? Why?
- fenestrated capillary endothelium freely filtering molecules <7000 daltons, with variable filtration up to 70 000 daltons - the endothelial Glycocalyx mainly filters proteins, fenestration mainly filter cells (60-80nm)
* Mesangial cells - contract in response to angiotensin 2 reducing surface area for filtration —>reduced GFR
* Negatively charged basemement membrane reducing filtration of negatively charged molecules
* Negatively charged podocyte foot processes with 3-4nm slits filtering mainly proteins
What is the reflection coefficient of the glomerular basement membrane
- Reflection coefficient = 1 as the glomerular membrane is essentially completely impermeable to protein
Draw a graph relating serum creatinine to renal function
What is creatinine
- Small endogenous molecule from skeletal muscle metabolism, eliminated by glomerular filtration and tubular secretion only (no reabsorption)
◦ Generally produced in a steady state
Define creatinine clearance
- Creatinine clearance is volume of plasma cleared of creatinine per unit of time (measured in mL/min or L/day)
Measurement of creatinine clearance relys on which principle>
- Measurement of creatinine clearance utilises Fick’s principle
◦ Renal clearance = amount of substance in urine per unit of time / plasma concentration of substance P
◦ Where amount of substance in urine per unit of time = urine concentration x urine flow
◦ Plasma concentration is stable and therefore arteriovenous differences do not need to be measured
What are the issues with measured creatinine clearance in the critically ill (2)
◦ Time delay in being able to calculate GFR especially in dynamically changing environments
◦ As creatinine is secreted into the PCT (10-20% at baselin) creatinine clearance will overestimate GFR; with declining kidney function secretion often remains intact and represents a greater proportion of measured creatinine clearance resulting in overestimation of GFR when low
Cockroft Gault equation
- CG (Cockcroft-Gault Equation): common method which has a correlation of ~0.83 with CrCl:
◦ CrCl = [(140−A) × W x S)] / (814 × Cr) , where:
‣ Cl = Clearance (mL/min), A = Age, W = Lean body Wt (kg)
‣ S = Sex coefficient (Male = 1, Female = 0.85)
‣ Cr = Creatinine in mmol/L (if mg/dL then use 72 instead of 814)
Problems with Cockroft Gault is divided into 3 factors
- Problems with the generalisations about weight and age
- Applying to critically ill
- Extra corpereal circuits
- Fluid resuscitation
- Muscle injury, sarcopenia, steriods, nutrition - Serum creatinine has a non linear association with Cr
What Formula average problems can you forsee with Cockroft Gault
◦ extremes of age
◦ different ethnicities,
◦ Extremes of muscle mass
◦ malignancy
◦ diet - increased Cr with increased dietary protein consumption, decreased with fasting and vegetarian diet
◦ drugs affecting tubular secretion
What critical illness factors influence Cr
◦ the amount of creatinine produced varies with muscle mass, nutrition, steroid use, muscle injury
◦ are modified by aggressive fluid resuscitation
‣ Dilutes serum creatinine making things appear better
◦ Extra-corpereal circuits e.g. CRRT and ECMO can mask raised creatinine by dilution, dialysing or adsorbing
Non linear association of Cr and renal function
- Where renal function is changing rapidly
- Cr only rises once >50% of renal function is lost
- More inaccurate the worse renal function is
Draw a graph representing a loss of renal function and rise in Cr
What is the range of molecular size able to be filtered at the glomerulus
‣ Capillary endothelium - large fenestrations
* <7000 daltons freely filtered
* 7000 - 70, 000 variably filtered
* Above 70k daltons cannot pass
Where are the kidneys from a surface anatomy perspective
T12 - L3
Gross anatomy of a kidney
◦ Paired, solid, bean shaped abdominal (retroperitoneal) organ
◦ Hilum on the medial side –> renal artery and vein, lymphatic supply, nerves and ureter
◦ Tough fibrous capsule - perirenal fat - renal fascia and pararenal fascia
Main substructural elements of a kidney
◦ Cortex:
‣ cortical labyrinth
‣ medullary rays/renal columns which ar extensions of the cortex penetrating into the medulla
◦ Outer medulla: inner stripe and outer stripe; multiple pyramids with the base at the corticomedullary junction and apices - the papilla - at the hilum draining into the ureters
What is the blood supply of the kidney
- Blood supply - paired arteries off the abdominal aorta renal arteries; R longer than left
◦ Venous drainage via renal veins into IVC
What is the innervation of the kidney
◦ efferent is strictly sympathetic, from T9-T13
◦ afferent (pain) via the least splanchnic nerve (T12)
Nephrons
- Number
- Types
◦ Functional unit of the kidney - 1 million/kidney
◦ Functional unit consists of glomerulus, proximal tubule, loop of Henle, dital tubule and collecting ducts
◦ Cortical nephrons: short-looped in the cortex
◦ Juxtaglomerular nephrons: have long loops of Henle, contribute the most to the process of producing concentrated urine and the efferent arteriole forms the vasa recta
Constant renal artery flow maintained between what ranges
MAP 70 -170
Where does the blood flow go in distribution in the kidney
95% cortex
5% to medullar
What is the renal oxygen extraction
10-15%
Renal oxygen extraction vs blood flow?
Stable as with increasing renal blood flow there is increasing function
Renal oxygen consumption is proportional to renal filtraiton and tubular sodium delivery
What % of the autoregulatory function of blood flow to the kidney does each unit do
50/35/15
Myogenic
tubuloglomerular feedback
Renin
How does the myogenic feedback system work
◦ Vasoconstriction in response to wall stretch (increased transmural pressure –> increased intracelular calcium concentration due to mechanically gated non-specific cation channels) –> membrane depolarisation –> vasoconstriction
◦ Constriction prooperotional to increase in pressure keeping flow constant
* This is a stereotyped vascular smooth muscle response, not unique to the kidney
How does tubuloglomerular feedback work
- Sensory - macula densa in the junction of the ascending limb of the loop of Henle/DCT
◦ Detects change int ubular flow rate via changing Na flux across its membrane
* Increased flow = increased perfusion pressure = release of adenosine and afferent arteriole constriction via extraglomerular Mesangial + granular cells in the walls of the afferent arteriole releasing renin
* Decreased flow leads to reduced adenosine release and subsequent NO release and renin
What escape mechanisms does the kidney have for reduced blood flow
‣ PGE2 + PGI2 act as escape mechanisms where renal blood flow is chronically reduced in times of stress to vasodilation and oppose the systemic vasoconstrictors
