Renal function

I. Introduction.

A. Kidneys - filter fluid from bloodstream into tubules, materials not needed stay in the tubules to be excreted; needed materials (ions, water) are reabsorbed to the blood; some material is actively pumped into the tubules for excretion.

- filtrate formed, as it passes through tubule its volume is reduced and composition altered -- wastes are eliminated, water and essential electrolytes and metabolites are conserved.

- the composition of urine can thus be highly varied -- homeostatic mechanisms minimize/prevent changes in ECF composition by changing amount of water and solutes in urine.

- regulate blood volume, chemical makeup of the blood; water and electrolyte balance, acid-base balance.

B. Ureters.

C. Urinary bladder.

D. Ureters.

II. Kidney functional anatomy.

A. Internal anatomy.

- renal capsule: fibrous connective tissue.

- cortex: light and granular.

- medulla - darker (reddish brown).

- medullary pyramids: cone shaped tissue, separated by cortex projections, renal columns.

- apex of medullary pyramids terminate in papillae.

B. Blood supply - kidneys receives 25% cardiac output per minute (1200 ml).

C. Nephrons: microscopic anatomy of kidney.

- structural and functional units of the kidney, responsible for urinary formation.

1. Glomerulus: tuft of capillaries.

- associated with the renal tubule.

- blind end of the renal tubule is cup-shaped, surrounds glomerulus -- Bowman's capsule.

- glomerulus and Bowman's capsule form renal corpuscle.

- glomerular capillaries are highly fenestrated.

- outer layer of Bowman's capsule -- parietal layer, simple squamous epithelium, no filtration function.

- inner layer of Bowman's capsule -- visceral layer, clings to glomerulus; formed by branching epithelial cells, podocytes; podocytes have numerous foot processes, pedicels, that form filtration slits.

- thus the glomerular caps and enveloping podocytes form a very porous filtration membrane -- solute rich filtrate thus enters Bowman's capsule; between the capillary endothelium and podocytes is a basement membrane.

2. Proximal convoluted tubule (PCT).

- reabsorbs substances from the filtrate.

- secretes substances into the filtrate.

3. Loop of Henle.

- hairpin loop, descending and ascending limbs.

- descending limb: freely permeable to water.

- ascending limb: freely permeable to NaCl.

4. Distal convoluted tubule (DCT).

- hormonally regulated reabsorption of H2O

- secretion.

5. Collecting duct (CD) - several DCTs empty into it.

- hormonally regulated reabsorption of H2O and NaCl.

D. Types of nephrons.

- some nephrons almost entirely in the cortex; very short loop of Henle -- cortical nephrons.

- other nephrons have a long loop of Henle which extends deep into the medulla -- juxtamedullary nephrons (15%).

F. Capillary beds in nephrons.

1. Cortical nephrons.

a. Glomerulus originates from afferent arteriole, empties into efferent arteriole; high blood pressure in the glomerulus, a specialization for filtration.

b. Peritubular capillaries arise from efferent arteriole; surround PCT, DCT, some of LH; empty into nearby venules; low pressure caps, very porous -- adaptations for reabsorption and secretion.

2. Juxtamedullary nephrons.

a. Glomerulus - as in cortical nephrons.

b. Peritubular capillaries - as in cortical nephrons.

c. Vasa recta: are thin walled looping vessels that parallel the Loop of Henle; they extend deep into the medulla and empty into nearby venules.

G. Vascular resistance along nephron circulation.

- blood pressure in glomerular caps about 55 mm Hg, however doesn't drop much across the capillary bed itself; pressure in peritubular caps is 8 mm Hg

- blood pressure decreases along nephron circulation from afferent arteriole to peritubular caps to vasa recta.

F. Juxtaglomerular apparatus.

- there is a close spatial relationship between PCT / DCT and afferent / efferent arteriole of glomerulus; where the DCT curves back between the afferent and efferent arterioles a group of cells are found predominantly in the walls of the afferent arteriole, JG cells; these cells sense blood pressure at the afferent arteriole, produce hormone renin.

- in the same location the walls of the DCT tubule contains specialized tubular cells, the macula densa, chemoreceptors and osmoreceptors -- monitor contents of DCT.

III. Renal physiology.

A. Introduction.

- 1000-1200 ml blood passes through the glomerulus per minute.

- thus, 650 ml/min plasma passes through the glomerulus per minute; 120-125 ml/min of plasma forced into tubules -- therefore you filter the equivalent of your plasma volume about 60 times a day, of your ECF volume 15 times per day, of your total body water 4 times per day.

- note that filtrate, however, very different from urine; filtrate is plasma minus its proteins; by the time the filtrate reaches the CD its volume has been reduced and its composition drastically altered.

- what remains in CD is urine -- metabolic wastes, unneeded substances.

- filter 180L/day -- urine volume only 1.5 L /day -- thus over 99% of filtrate is reabsorbed.

- thus renal function involves three basic processes, glomerular filtration, tubular reabsorption, and tubular secretion.

B. Glomerular filtration

- fluids/solutes moved across a membrane by hydrostatic pressure.

- filtration membrane very leaky and glomerular blood pressure high compared to other caps.

1. Characteristics of glomerular capillaries: glomerulus is a very efficient filter, glomerular caps form 100X more filtrate than other caps.

a. Filtration membrane or barrier -- neutral substances with effective molecular diameters of less than 4 nm are freely filtered, filtration of neutral substances with diameters of more than 8 nm approaches zero -- between these values filtration is inversely proportional to diameter

i. fenestrated capillary endothelium

ii. visceral membrane of Bowman's capsule -- podocytes with pedicels, filtration slits.

iii. intervening basement membrane -- size exclusion and charge exclusion of plasma proteins.

- filtration coefficient (Kf) for glomerular capillaries is much greater than that found in other capillary beds; Kf is a function of total capillary surface area as well as the permeability per unit surface area.

b. Glomerular net filtration pressure high compared to other caps -- 10 -15 mm Hg throughout capillary bed

- diameter of efferent arteriole smaller that that of afferent arteriole.

- forces involved in regulation of filtration, Starling forces

i. filtration pressures: blood hydrostatic pressure (55 mm Hg) and Bowman's capsule osmotic pressure (negligible).

ii. reabsorption pressures: blood osmotic pressure (30 mm Hg close to afferent arteriole) and Bowman's capsule hydrostatic pressure (15 mm Hg).

- thus  net filtration pressure is 10 mm Hg 

2. Glomerular filtration rate (GFR)

- total amount of filtrate formed by the kidney per minute, 125 ml/min; measured by calculating clearance for inulin or creatinine.

- depends on the surface area available for filtration, permeability of the filtration membrane, and net filtration pressure (GFR directly proportional to it).

- however, when BP in range of 80-180 mm Hg, GFR constant!!!

- this is important because changes in GFR can dramatically influence the amount and composition of urine produced and thus the volume and composition of blood -- thus very important to keep GFR constant within a wide range of BP.

a. Regulation of GFR - renal autoregulation.

- an intrinsic property of the kidneys.

i. Myogenic mechanism

- increased BP at afferent arteriole causes afferent arteriole constriction, decrease blood flow (BF) to glomerulus, decrease in glomerular BP, maintaining GFR stable.

ii. Tubuloglomerular feedback

- carried out by macula densa cells of JG apparatus.

- an increase in BP leads to momentary increased GFR -- this will lead to increased filtration, increased filtrate flow, decreased reabsorption, and NaCl concentration in tubule increases; changes in NaCl concentration detected by MD cells which in turn release a vasoconstrictor substance that acts on the afferent arteriole -- decreased BF to afferent arteriole, decreased glomerular BP, GFR stabilized.

- a decrease in BP has opposite effects.

b. Regulation of GFR - sympathetic innervation to afferent arteriole.

i.  -  if blood pressure drops -- hemorrhage or severe dehydration, for example:

ii.  if blood pressure dramatically raised  -- converse is true

c.  Regulation of GFR -- renin-angiotensin-aldosterone system