Functions of the Kidneys: Make urine pH regulation of the blood Maintain electrolyte balance of the blood Aid the liver in detoxification of the blood Regulate BP and blood flow Conservation of valuable nutrients Make bicarbonate ions, conserve Na, K, Cl and other valuable ions

The Kidney: Anatomy 2 kidneys – left and right Located retroperitoneal Adrenal glands sit on top, located medially Adipose tissue surrounds these organs – act as insulators/shock absorbers and helps keep organs in place Nephrons – functional & structural unit of the kidneys. Kidneys - Gross Anatomy:

- Outermost layer: Tough fibrous capsule - Cortex: Outermost layer in contact with capsule - Cortical nephrons are

located in this region. - Renal Medulla – pyramid shaped structure stretching from cortex to renal

sinus.

- Renal Pyramid - pyramid shaped with base facing the cortex and apex facing the renal pelvis. Loop of Henle and collecting tubes can be found in this area.

- Renal Column is a band of cortical tissue that extends down between the renal pyramids.

- Renal Papilla: tip of renal pyramid that drains urine from the medulla into minor calyx - major calyx - renal pelvis – ureter – bladder – urethra - outside.

- Ureter drains into urinary bladder – temporary storage site for urine - Urethra are the tubes that connect with the outside - Hilus is the entry way for renal veins, arteries and nerves – usually

sympathetic nerves

Nephron: 2 types - Cortical nephrons – account for 80% of the nephrons – responsible for bulk of kidney function. Juxtamedullary nephrons – account for 20% of nephrons: these nephron types have long Loop of Henles and are instrumental in maintaining water conservation in the body. Blood supply in the Kidney:

The afferent delivers blood into the renal corpuscle, the efferent delivers blood away from the kidney

Blood supply in the kidneys.

Nephrons: made up of 2 components:

- Renal Corpuscle – made up of an epithelial cup shaped structure called the Bowman’s Capsule: the glomerulus – which is the filtration unit of the kidneys and the Bowman’s space – which holds the filtrate.

- Renal Tubules composed of: o PCT – 65% of absorption occurs here o Loop of Henle – thin descending loop and thick ascending

loop o DCT – major site of secretions.

As the filtrate travels through the tubules of the kidneys, nutrients, salts, bicarbonate ions are reabsorbed back into the blood. Secretions are added back into the filtrate, e.g. K/H/Urea/Uric acid and toxins – these are solutes that the body does not need or are harmful to the body. Each nephron empties into the collecting tubule system that carries urine away from the nephron. Collecting tubules are impermeable to water, unless they are under the influence of ADH.

The afferent arteriole is larger in diameter than the efferent arteriole. This difference creates increased arterial pressure inside the glomerulus, which results in an overall positive force that filters plasma out of the arteriole and into the Bowman’s space. Typical arteriole pressures are 40-45 mmHg. Inside the glomerulus, typical pressures are 55-60 mmHg. This small difference generates a positive NFP, where GFR are proportional to NFP.

Structure of the Renal Corpuscle: The glomerulus capillary is covered with fenestrated epithelium cells. Large cells called Podocytes cover these fenestrate endothelium cells. Podocytes have long processes and when these processes fuse they form feet called pedicels. Pedicels form filtration slits between adjacent pedicels. Material must be small enough to pass out through the fenestrae, basement membrane and filtration slits. Fluid in the blood is mechanically filtered by size through 3 layers:

1. Fenestrated endothelium, 2. Shared basement membrane 3. Filtration slits

Since the inner epithelial cells are fenestrated and the long processes of the podocytes form slits – both of these together, along with shared basement membrane, form the filtration membrane that filters blood plasma in the kidneys.

Schematic of Glomerular Capillary with Visceral Layer of

Bowman’s Capsule (formed of Podocyte)

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Structure of the Nephron: Renal tubules are composed of different types of epithelial cells, depending on cell function: PCT – simple cuboidal epithelial cells with brush border – responsible for absorption of 65% of filtrate Descending loop of Henle – simple cuboidal cells: permeable to water and solute. Ascending loop of Henle – thicker loop composed of cuboidal cells: impermeable to water, permeable to NaCl DCT – simple cuboidal cells with no brush border. Cells are sensitive to aldosterone and this is the site of secretions of H & K ions in exchange for Na ions. Juxtaglomerulus Appartatus: Composed of 2 types of cells that work in conjunction with each other. Macula Densa – specialized cells of the DCT: act as osmoreceptor cells that monitor blood volume/blood pressure +/or osmolarity of plasma. Juxtaglomerulus cells which are specialized smooth muscle cells of the afferent arteriole. These smooth muscle cells contract when stimulated by the sympathetic nervous system and secrete renin. Glomerular Filtration rate is the amount of filtrate produced by the kidneys per minute (125ml/min). This rate is dependent on 3 components:

1. Hydrostatic pressure created by the difference in diameter between the afferent and efferent arterioles.

2. Opposing hydrostatic pressure created by the fluid build up inside the Bowman’s capsule.

3. Opposing osmotic pressure created by the colloid proteins content in the filtrate. This osmotic pressure tends to draw water into the capillary from the bowman’s space.

The overall NFR is usually positive favoring the flow of filtrate out of glomerulus and into the Bowman’s capsule where it makes it way into the PCT and onwards towards the bladder. Both the afferent & efferent arterioles are composed of smooth muscle and are innervated with sympathetic neurons. Therefore their diameters can be changed, depending on GFR and neural stimulation.

- Afferent arteriole radius is directly proportional to GFR: increase in its radius will directly increase the rate of GDF flow and vice versa.

- Efferent arteriole radius is indirectly proportional to GDF flow; when you increase the radius, you decrease the GDF rate, and vice versa.

- Increase in capillary HP will increase GDF - Increase in Capsular HP will decrease GDF - Increase in colloid osmotic pressure will decrease GDF

Plasma and glomerular filtrate are identical except filtrate has no large proteins in it. Urine composition includes urea, creatinine, uric acid, as well as K and Phosphate ions. Urine Formation: Reabsorption & Secretion: Tubular secretions add to urine volume, e.g. K, Creatinine Tubular reabsorption subtract from urine volume, e.g. Na, Ca, Cl Glomerular filtrate adds to urine volume

Glomerular Filtration rate: Net Filtration rate = HP (glomerular) – [HP (capsule) + OP (colloid protein osmotic pressure)]. NFR is usually positive. GFR is directly proportional to radius changes in afferent arteriole and GDF is inversely proportional to efferent arteriole. Vasoconstriction (incr. in sympathetic stimulation) Afferent = dec. GDF flow Efferent = inc. in GDF flow Vasodilation (dec. in sympathetic stimulation) Afferent = inc. GDF flow Efferent = dec. in GDF flow Increased HP capillary = inc. GDF flow Increase in HP Capsule = dec. in GDF flow Increase in Colloid osmotic pressure = dec. in GDF flow GFR is equivalent to NFP, which is about 180L/day. Urine output ranges from 0.5L to 2.5L/day. Glomerular reabsorbs about 99% of filtrate that passes through it every day.

Kidneys are very sensitive to changes in GDR Flow rates. Blood pressure is the most important factor that influences GDF rates. A 10% drop in mean arteriole pressure will severely damage the glomerulus filtration rate. Changes beyond this can shut down kidney function completely.

Kidneys exert control over their environments by three main mechanisms:

- Autoregulation at the local level, which is fast. - Neural regulation – very fast - Hormonal regulation, which can take hours or days to work e.g., ADH and

aldosterone, renin, ANP’s.

Autoregulation occurs via two mechanisms:

- Myogenic mechanism whereby smooth muscle tends to contract when stretched due to increase BP. Contraction of the afferent arteriole results in increase in GDF; opposite is also true.

- Tubuloglomerular mechanism whereby the MD cells sense changes in GDF flow or osmolarity of plasma. Changes are relayed to JG cells, these which contract and release renin, which activates the renin/angiotensin cascade ultimately results in aldosterone release and a decrease in afferent radius and GDF flow.

- Neural regulation: Fast response

- Usually sympathetic stimulation = results in vasoconstriction which decreases afferent arteriole radius and decreases GDF flow.

- During times of stress or emergency, blood is shunted to vital organs and not to non-vital organs. As a result, afferent radius is decreased resulting in a decrease in GDF – water conservation occurs.

- Sympathetic stimulation stimulates JD cells to secrete renin. - Neural control may override local regulation.

Hormonal Regulation = slower; may take hours or days to regulate

- Activation of renin (AG apparatus)/angiotensin cascade = stabilizes BP and blood volume.

- Angiotensin 2 is a potent vasoconstrictor as well as stimulating the release of aldosterone from the adrenal cortex. Aldosterone conserves Na and water, which raises BP, BV, and osmolality.

- ANP: Opposes angiotensin/aldosterone/ ADH activation o Increases fluid & Na loss from kidneys o Dilates afferent arterioles = increases GDF flow o Increased urine production

Renin-aldosterone System: respond to changes in Na/Water concentrations. Angiotensinogen is produced by the liver when the kidneys detect low BP, BV, and low Na concentrations. Renin is produced by JG apparatus under sympathetic stimulation when BP is low and converts angiotensinogen into angiotensin 1. ACE is produced by type 1 alveolar cells: converts angiotensin 1 into angiotensin 2. Angiotensin 2 is a potent vasoconstrictor as well as stimulating the release of aldosterone from adrenal cortex.

- Results in Na & water conservation - Activation of thirst receptors in hypothalamus - Increased water absorption under influence of ADH - BP stabilized and ECF returned to normal levels

Renal Corpuscle –site where filtrate is produced by passage through glomerular filtration membrane. Filtration is a mechanical process based on size. PDT – 65% of filtrate is reabsorbed here – food, salt, bicarbonate Descending loop of Henle – site of water reabsorption and urea secretion Ascending loop of Henle – impermeable to water, site of NaCl absorption DCT – active secretions of K, CL, HCO3 Collecting tubules – reabsorption of water under influence of ADH and urea. Reabsorption by tubular cells is a selective process

- Diffusion - Osmosis - Facilitated Transport – Active, Carrier mediated, Cotransport & Anti-

transport Tubular cells have a transport maximum for most substances besides Na. Transport mechanisms can be overwhelmed resulting in valuable solute being excreted in the urine. Tm is the rate at which solutes can be transported.

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Overview of Renal Function Figure from: Saladin, Anatomy & Physiology,

McGraw Hill, 2007

You should know

what is moved (red

arrows indicate the

important items),

and in what part of

the nephron they

are moved.

Keep in mind:

Where Na+ goes,

H2O and Cl- usually

follow.

**See the Summary

Table in your Study

Guide for Exam 4

*

*

Renal Threshold is the threshold over which specific solute will not be reabsorbed back into the body and will be excreted by the kidneys. Peritubular capillaries are well suited to reabsorption since

- low HP pressure - high degree of permeability - high colloid osmotic pressure which draws fluids into tubules

Reabsorption at PCT: Na/K antiport system: Na is reabsorbed by the body and K ions are secreted into tubular lumen in a one for one trade. The tight junctions between cells of the PCT are slightly leaky so water, urea, Na, Cl can get back into the blood via the gradient created by the Na/K antiport system. The active transport of Na into the tubular cell is the mechanism by which all the other substrate is pulled out of tubular lumen and back into the bloodstream. The Na/K antiport results in Na gradient that drags glucose, aa’s, and other electrolytes into the bloodstream and out of the tubular fluid by the creation of a vacuum.

Tubular secretions in PCT & DCT: Secretions add to urine volume. Provides the body a mechanism to eliminate toxins, drugs, H, K ions.

9

Reabsorption in the PCT Substance Mechanism of

Reabsorption

Notes

Na+ (Cl-)

Primary Active Transport Na+ reabsorption is the

driving force for most other

reabsorption

H2O Osmosis Closely associated with

movement of Na+

(Obligatory water

reabsorption)

Glucose Secondary Active transport Limited # of molecules can

be handled

(Tm = 375 mg/min);

attracts H20

Amino Acids Secondary Active transport Three different active

transport modalities; difficult

to overwhelm

Other electrolytes Secondary Active transport

The Na/K antiport system will also exchange Na ions for H ions, giving the kidneys the ability to regulate plasma pH. Reabsorption of Na ions in the DCT are under the influence of aldosterone – a mechanism to conserve Na and water in the body. Collecting Tubules: Provide the body with the means of reclaiming H20 or eliminating it from the body. Collecting tubules are under the influence of ADH – conservation of water only. Loop of Henle: The role of the loop of Henle is to maintain body fluids at 300 mOsm/liter. This is accomplished by varying the concentration of urine using the counter current multiplier. Water moves passively by osmosis. Body can maintain osmolarity of blood by varying the amount of water excreted from the body. If the plasma is hypotonic, excrete more dilute urine from kidneys, if plasma is hypertonic, the kidneys will retain more water. Urine concentration can by varied via 2 mechanisms:

- Counter Current Multiplier utilizing the salt gradient created by the hypertonicity of the peritubular fluid.

- Varying the permeability of the collecting tubules to water via ADH. The descending loop is permeable to water only so as water leaves the tubule, the osmolarity of the tubular fluid increases from 300 to 1200 Osm/l, its most concentrated form. Water moves out passively by osmosis and the outflow of water is dependent upon the osmotic gradient in the medulla. The ascending loop is impermeable to water and as NaCl ions leave, the osmolarity of the tubular fluid decreases from 1,200 to its most dilute form, 100 Osm/l. Exchange occurs between the fluids moving in opposite directions and this exchange creates the salt gradient in the medulla of Juxtamedullary nephrons. This gives the body the ability to reabsorb large volumes of water later at the collecting ducts, if needed, under the influence of ADH. The vasa recta capillaries flow in the opposite direction to the flow of glomerular filtrate through the nephron and help to maintain the salt gradient by returning the water and NaCl in the medulla to general circulation and thereby allow the countercurrent multiplier to work. The vasa recta also delivers blood to the medulla.

Under the influence of ADH, the DCT and collecting tubules are permeable to water (facultative water absorption). In the absence of ADH, they are impermeable to water. DCT & Collecting tubules are also sensitive to aldosterone – which helps to conserve Na ( and water).

Diuretics promote loss of water from the body. Anything that increases the osmolarity of the tubular fluid, will draw water into tubular fluid, can act as a diuretic. Urine is composed of 95% water and its composition can vary depending on diet and level of activity. Other components of Urine include:

- urea (50% is excreted) - uric acid (90% is reabsorbed) - 100% of creatinine is excreted - Electrolytes - Urochrome - Trace amounts of aa’s

Min amount of urine production/day is 0.6L to maximum 2.5L/day. Renal failure occurs when output is less than 25ml/hour.