Physiology for MRCEM Primary

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Renal physiology

Renal functional unit

[box type=”download”] Functional anatomy of the renal tract Note: you should cross-reference this section with the anatomy curriculum. Macroscopic structure of the kidney:  Cortex + medulla and the principal components of each (e.g. location of glomeruli)  Composition of the nephron (Bowman’s capsule, tubules etc)  Function (in broad terms) of each component of the nephron  Appreciation of how nephron anatomy reflects these functions [/box]

The kidneys help to maintain the composition of extracellular body fluids, and regulate ions (e.g. Na+, K+, Ca2+, Mg2+), acid–base status and body water.
They also have an endocrine function.
Plasma is filtered by capillaries in the glomerulus, and the composition of the filtrate is modified by reabsorption and secretion in the nephrons.
The average urine output is ∼1.5 L per day.


Gross structure

The kidneys are located retro-peritoneally.
The renal artery and vein, lymphatics and nerve enter the kidney via the hilus, from which the renal pelvis, which becomes the ureter, emerges.
The kidney is surrounded by a fibrous renal capsule.
Internally, the kidney has a dark outer cortex surrounding a lighter medulla, which contains triangular pyramids.
The cortex contains the glomerulus and proximal and distal tubules of the nephrons, whilst the loop of Henle
and collecting ducts descend into the medulla.
Each kidney contains ∼800 000 nephrons.
The collecting ducts converge in the papilla at the apex of each pyramid, and empty into the calyx (plural:
calyces) and thence renal pelvis.
Urine is propelled through the ureter into the bladder by peristalsis.


The nephron

Bowman’s capsule surrounds the glomerular capillaries, which collects filtrate, followed by the proximal tubule, loop of Henle, distal tubule and early collecting duct.
There are two types of nephrons –
cortical nephrons: ∼85%; glomeruli in the outer 70% of the cortex and short loops of Henle
juxtamedullary nephrons: ∼15%; glomeruli close to the cortex–medulla boundary and long loops of Henle.
The glomerulus produces ultrafiltrate from plasma.
The proximal tubule is convoluted but straightens before becoming the descending limb of the loop of Henle in the medulla.
Walls lined by columnar epithelial cells with a brush-border of microvilli.
Tight junctions close to the luminal side limit diffusion through gaps between cells.
The basal or peritubular side of the cells shows considerable interdigitation, which increases the surface area. The term lateral intercellular space is often used to describe the space between the interdigitations and basement membrane, and between the bases of adjacent cells.
The main function of the proximal tubule is reabsorption.
The thin part of the loop of Henle is formed from thin, flat (squamous) cells, with no microvilli. The thick ascending loop of Henle has columnar epithelial cells similar to the proximal tubule.
The loop has modified macula densa cells near by the juxtaglomerular apparatus in the cortex.
The loop of Henle is important for the production of concentrated urine.
The distal tubule is functionally similar to the cortical collecting duct. Both contain cells similar to those in the thick ascending loop of Henle.
In the collecting duct, these principal cells are interspersed with intercalated cells of different morphology and function; these play a role in acid–base balance.
The collecting duct plays an important role in water homeostasis.


Renal blood supply and drainage

[box type=”download”]  Appreciation of the rich vascularity of the kidney and the rationale for this  Structural arrangement of afferent and efferent arterioles  Importance of renal autoregulation and a simple overview of factors affecting it[/box]

Renal circulation

The kidneys receive ∼20% of cardiac output.
The renal artery enters via the hilus and divides into interlobar arteries running between the pyramids to the cortex–medulla boundary, where they split into arcuate arteries.
Interlobular arteries ascend into the cortex, and feed the afferent arterioles of the glomerulus.
The capillaries of the glomerulus are the site of filtration, and drain into the efferent arteriole (not vein).
Afferent and efferent arterioles provide the major resistance to renal blood flow.
Efferent arterioles branch into a network of capillaries in the cortex around the proximal and distal tubules (peritubular capillaries).
Capillaries close to the cortex– medulla boundary loop into the medulla to form the vasa recta surrounding the loop of Henle; this provides the only blood supply to the medulla.
All capillaries drain into the renal veins.
Ninety per cent of the blood entering the kidney supplies the cortex, giving a high blood flow (∼500 mL/min/100 g) and a low arteriovenous O2 difference (∼2%).
Medullary blood flow is less (20–100 mL/min/100 g).


Regulation of renal blood flow.

Differential constriction of afferent and efferent arterioles strongly affects filtration.
The kidneys have a high degree of autoregulation, both by the myogenic response and via the macula densa, which detects high filtration rates and releases adenosine, which constricts afferent arterioles, so reducing filtration.
Noradrenaline (norepinephrine) from renal sympathetic nerves constricts both afferent and efferent arterioles, and increases renin and thus the production of angiotensin II (a potent vasoconstrictor).
Many peripheral vasoconstrictors (e.g. endothelin, angiotensin II) cause the release of vasodilating prostaglandins in the kidney, so protecting renal blood flow.


Hormones and the kidney

Renin is produced by the juxtaglomerular apparatus and promotes the formation of angiotensin.
Erythropoietin is synthesized by interstitial cells in the cortex.
Vitamin D is metabolized in the kidney to its active form (1,25-dihydroxycholecalciferol), which is involved in Ca2+ and phosphate regulation.
Various prostaglandins are also produced in the kidney, and affect renal blood flow.


Micturition

The constriction of smooth muscle in the bladder wall (detrusor muscle) expels urine.
Micturition is initiated by a spinal reflex when urine pressure reaches a critical level, but is strongly controlled by higher (voluntary) centres.
The neck of the bladder forms the internal urethral sphincter; the external sphincter is formed from voluntary skeletal muscle around more distal regions of the urethra.