Basic Renal Anatomy and Physiology Flashcards
Early development of the kidney
First, the pronephros forms. This is a simple array of large tubes.
Then, this develops into the mesonephros, containing both tubes and filtering apparatuses.
Part of the mesonephros will degenerate and form the metanephros, the segment of the tubules which gives rise to the ureteric bud. This bud invades the surrounding mesenchymal tissue to form the body of the kidney. Signaling from these buds leads to the formation of nephrons and then the metanephric mesenchyme converts to the renal epithelia
Ureteric bud development
Rough structure of a nephron
Developmental ascent of the kidneys
CAKUT
Cognenital abnormalities of the kidney and urinary tract
These range from a double ureter to an obstruction at the junction of the renal pelvis to the origin of the ureter. There can also be abnormalities of the urethra and bladder. One common abnormality is “posterior urethral valves” which leads to obstruction of the bladder, oligohydramnios and the consequences of this is reduced amniotic fluid
Wilm’s Tumor
The most common renal malignancy of childhood. It develops because of a deletion in the tumor suppression gene WT1 (Wilm’s tumor 1). They are usually large but encapsulated and the pathology is reminiscent of early renal development.
Unilateral renal agenesis
Will be asymptomatic (this is fairly common and thought to occur 1 in 1,000 births).
When it is bilateral, there will be oligohydramnios, and this can lead to inadequate fetal lung development and disfigurement of the growing fetus because the fetus is compressed against the placenta.
Blood flow to the kidneys
Three layers of renal capillaries
- Fenestrated endothelium
- Specialized basement membrane
- Podocytes
Podocytes
Unique type of visercal epithelial cell that lines the renal capillaries.
These cells have a series of extensions or “feet” that interdigitate with neighboring cells to form specialized junctions that allow filtration. They also help support the open capillaries in a fashion analogous to the architectural flying buttress.
Hydrostatic and oncotic pressure gradient across renal capillaries vs distance
Important physiologic distinctions between glomerular and normal capillaries
- Glomerular capillaries have a higher hydraulic pressure
- That pressure changes very little from beginning to end (~constant slope)
- The oncotic pressure of the capillary rises asymptotically with the hydrostatic pressure as the limit (while it is constant in normal capillaries)
The “kidney function” and SNGFR
The “kidney function” of an individual patient is the sum of the filtration of each of the glomeruli.
The single nephron glomerular filtration rate (SNGFR) is a model on the level of an individual nephron. This follows the function:
SNGFR = k x A x (ΔP - Δπ)
Where k is hydraulic permeability and A is surface area.
Clearance
Also called the glomerular filtration rate (GFR). The clearance of a substance is the volume of plasma from which all the substance is removed and excreted per unit time.
Clearance of a substance = GFR if the substance is:
- Freely filtered
- Not secreted
- Not absorbed
U is the concentration of a substance in the urine. V is the urine flow rate and P is the concentration in the plasma
Inulin
A natural, easily measurable polysaccharide that has been used to study renal clearance because it meets the criteria of the clearance equation. When injected into humans or dogs, it rapidly appears in the urine.
Calculating renal blood flow from lab measurements
This assay utilizes para aminohippurate, or PAH, which is so readily excreted by the glomerulus that it does not make it into the renal vein, thus delivery = excretion.
Creatinine
A normal serum creatinine for a man is about 1.0 mg/dL and normal values for women tend to be a little lower, perhaps 0.7-0.8 mg/dL.
Creatinine slightly overestimates the GFR.
Creatinine clearance equation
eGFR equation
GFR (mL/min/1.73 m2 ) = 175 × (Scr)e-1.154 × (Age)e-0.203 × (0.742 if female) × (1.212 if African American)
No need to memorize this, but know it is the more accurate equation, but it too is still an estimate. Depsite this, it is now looked down upon due to its use of ‘race’ which is not particularly useful and was not even determined with any examination of ancestry of this population. It also often overestimates kidney function of African Americans, who have some of the highest risk for ESRD. Better off ignoring the last part of the equation.
BUN
Blood urea nitrogen
Formerly used as another assessment of renal function, still used sometimes, but not as useful as creatinine.
Renal autoregulation relationship
The kidney’s vasculature autoregulates incoming pressure across a wide range of pressure, but is not all encompassing. Too low and there is insufficient pressure to perfuse the kidney and filter in glomeruli. Too high and the glomeruli get damaged by sheer stress.
Sympathetic and juxtaglomerular autoregulation of renal perfusion
Sympathetic: Efferent nerves from the thoraco-lumbar sympathetic chain and the celiac plexus supply the kidney and release norepinephrine which results in vasoconstriction.
Juxtaglomerular: Juxtaglomerular cells of the afferent arteriole release renin in response to decreased blood pressure. This results in angiotensin II production downstream in the lungs, locally constricting renal blood vessels and systemically affecting blood pressure and fluid retention as well.
Most important of the many roles of angiotensin II
- Potent systemic vasoconstriction
- Maintenance of glomerular filtration rate
- Sodium retention (especially in the proximal tubule)
- Stimulation of aldosterone release
- Cardiac remodeling
Role of prostaglandins in renal autoregulation
Allow for renal vasodilation even when there is systemic vasoconstriction
Macula densa
Portion of the distal convoluted tubule which comes back up to meet the glomerulus again, making tubuloglomerular feedback possible.
If the flow is very high in the macula densa, a signal is sent to the glomerulus to limit filtration by vasoconstriction of the afferent arteriole. If the flow in the macula densa is reduced, then mediators release prostaglandins to vasodilate the afferent arteriole and increase filtration.
Which renal vein is longer?
The left! It has to cross over the aorta in order to make its way to the inferior vena cava. In transit, it passes between the superior mesenteric artery and the aorta.
Abdominal aorta
Cortical-medullary imaging phase
Phase after injecting contrast at which the contrast is in the cortex of the kidney, but has not yet made its way into the medullary renal pyramids and glomeruli.
Useful for imaging purposes and demostrates the circulation of the kidney.
~30 seconds post-bolus
Fascia surrounding the kidnies
Isolated anatomy of the renal and adrenal vasculature
Ureter cross-sectional histology
Vesico-ureteral junction
The following is a transmission electron micrograph showing kidney microcircullation. What are the vessels shown?
Nephron structure
Nephron with associated vasculature
Structure of Bowman’s Capsule
Scanning EM of a podocyte
What determines glomerular filtration of a substance (ignoring reabsorption for now)
Nephron tubule reabsorption summary
Major machinery within a proximal tubule cell
The Na-K ATPase on the basolateral side and all of the many mitochondria in the cell create a Na+ gradient, which is then utilized by the Nhe3 exchanger on the apical side to pump out protons so bicarbonate and other pH-dependent substances may be reabsorbed. Brush-border carbonic anhydrase aids with this process.
Ammoniagenesis within proximal tubule cells
Proximal tubule cells dispose of nitrogenous waste in the form of glutamine by removing the nitrogen in the form of NH4 and secreting it, preserving the glucose backbone and making a few molecules of bicarbonate in the process.
Thick ascending loop of Henle cell
Distal convoluted tubule cell
Two major cells of the collecting duct
Principal cells and alpha-Intercalated cells
The SGLTs
Expressed in the proximal tubule cells.
How will afferent and efferent arteriole dilation or constriction affect the renal blood flow through capillaries and the GFR? Fill out the table below.
Nephron function with and without vasopressin
Takeaways for all nephron segments
Countercurrent multiplier system
NCC
Na+/Cl- symporter in distal convoluted tubule. Target of thiazide diuretics.
