Renal System

Question 1

What is a gross anatomy of renal system?

Answer 1

1) Kidneys (a pair of bean-shaped organs) extend from inferior vena cava and abdominal aorta.

2) There are adrenal glands on the top of each kidney

3) Ureters connects kidneys to urinary bladder

4) Urethra releases urine from urinary bladder outside.

Question 3

Where are kidneys located?

Answer 3

Retroperitoneally at the level of the lower ribs.

Question 4

What is the gross anatomy of the kidney?

Answer 4

1) Outer cortex, contains:
- afferent arterioles
- cortical nephrones (fully)
- arcuate arteries (horisontally)
- arcuate veins (horisontally)
- juxtamedullary nephrones (glomeruli, proximal and distal tubules)

2) Inner medulla:
- arcuate arteries (vertically)
- arcuate veins (vertically)
- juxtamedullary nephrons (loop of Henle, longer than in cortical nephrons)

3) Nephrones are organized into renal pyramids

4) the urine from all nephrones is collected in renal pelvis before entering ureter.

Question 5

What is nephron and its gross anatomy?

Answer 5

Nephron is the smallest functional unit of the kidney which is a series of convoluted small tubes with associated small vessels.

Produce urine by filtering and modifying the concentrations of solutes in blood plasma through reabsorbtion and secretion.

1) Glomerulus with afferent and effetrent arterioles

2) Bowman’s capsule around glomerulus

3) Proximal convoluted tubule

4) Descending limb of loop of Henle (has shorter thicker part)

5) Ascending limb of loop of Henle (has longer thicker part)

6) Distal convoluted tubule

7) Collecting duct

Question 7

What are the 4 key functions of the kidneys?

Answer 7

1) Filtration:
- happens at glomerulus and Bowman’s capsule (renal corpuscle)
- blood plasma without most proteins enters nephron lumen, forming filtrate

2) Reabsorbtion:
- some solutes from the filtrate are transported back to blood
- involves peritubular capillaries and vasa recta (around loop of Henle)

3) Secretion:
- some solutes are transported into filtrate
- also involves peritubular capillaries and vasa recta

4) Extretion:
- from lumen to the outside of body

Question 8

What is the state of filtrate in the proximal convulated tubule?

Answer 8

• 180 L/day
• 100% volume
• 300 mOsM

This is almost identical to blood plasma composition.

70% of filtrate (most of water and solutes) are isosmotically reabsorbed at the proximal convoluted tubule.

Some metabolites and xenobiotics such as penicillin are secreted in the proximal convoluted tubule.

Question 9

What is the state of filtrate in the beginning of loop of Henle?

Answer 9

• 54 L/day
• 30% volume
• 300 mOsM

In loop of Henle, more ions than water are reabsorbed, decreasing osmolarity in the next step.

Interstitial fluid (countercurrent to the filtrate moving through nephron) in the medulla becomes more concentrated, as a result.

Question 10

What is the state of the filtrate at the end of loop and Henle and beginning of distal convoluted tubule?

Answer 10

• 18 L/day
• 100 mOsM
• 10%

Water and ions are reabsorbed or secreted by distal convoluted tubule and collecting duct according to body needs and regulated by antidiuteric hormone (vasopressin).

Question 11

What is the final composition of the filtrate in the end of distal convoluted tubule and collecting duct?

Answer 11

• 1.5 L/day
• 50-1200 mOsM
• ~1% of volume

Question 12

How much blood passing through glomerulus is actually filtered?

Answer 12

20% only.

Question 13

What are the filtration barriers in the renal corpuscle?

Answer 13

1) Special type of leaky endothelium (fenesterated endothelial cells):
- contains pores 50-300 nm wide
- the diameter of pores can change according to paracrine and endocrine regulation. This influences glomerulal filtration rate.
- filter out blood cells

2) glomerular basement membrane:
- ribbon like extracellular matrix made of collagen, laminins, nidogens and sulphate proteoglycans
- filters out larger proteins, often by their negative charge

3) podocytes:
- highly branched cells surrounding glomerulus
- form zig-zag shaped filtration slits
- filter out smaller proteins

Question 14

What are the features of glomerulal filtration rate?

Answer 14

• volume of fluid filtered in glomerulus per time
• relatively constant
• controlled by changing diameter of the afferent and effetent arterioles
• net filtration pressure (10 mm Hg) depends on downward hydrostatic (blood) pressure (55 mm Hg), opposing colloid osmotic pressure (-30 mm Hg) and opposing filtrate pressure (-15 mm Hg).
• filtration coefficient depends on glomerular surface area and permeability of filtration slits.

Question 16

What is the difference between afferent and efferent arterioles?

Answer 16

Afferent arteriole (entering glomerulus) is slightly bigger in diameter than effetent arteriole (exiting glomerulus). This creates pressure gradient, allowing more efficient glomerulus filtration.

Question 17

What is juxtaglomerular apparatus?

Answer 17

Bunch of cells (macula densa and granular cells) connecting glomerulus (between afferent and efferent arterioles) to loop of Henle.

Macula densa secretes paracrine signals (renin) which change afferent and effetent arterioles diameter according to the signals of distal tubule flow. This influences glomerulal filtration rate (GFR).

Question 18

How different solutes of filtrate are reabsorbed in the proximal convoluted tubule?

Answer 18

• water: osmosis
• Na+: active transport, transepithelial
• K+ and Cl-: passive transport, paracellular
• Ca2+: passive transport, both transepithelial and paracellular
• glucose, amino acids and other organic: secondary active transport, coupled with Na+
• urea: passive transport, follows gradient produced by active Na+ transport
• tiny proteins (albumin): endocytosis (active by default)

Question 19

Which substance is normally 100% reabsorbed in the proximal convoluted tubule?

Answer 19

Glucose.

Electrolytes are further reabsorbed in the loop of Henle, urea is secreted in the loop of Henle.

Question 20

Which substances undergo regulated absorbtion in the distal convoluted tubule and collecting duct?

Answer 20

Water, Na+ and K+

The rest are just reabsorbed.

Question 21

What is the difference between transepithelial transport and paracellular pathway?

Answer 21

Transepithelial transport: solutes crosses whole cell, entering apical and exiting basolatetal membrane.

Paracellular pathway: solutes go between cells.

Question 22

What is the difference in osmolarties in cortex and medulla?

Answer 22

In cortex: always 300 mOsM, isosmotic to plasma.

In medulla: osmolarity gradually increases (300 -> 600 -> 900 -> 1200 mOsM). Creating this difference helps to reabsorb water in the loop of Henle.

Question 23

What is the difference in functions between descending and ascending limbs of loop of Henle?

Answer 23

Descending: only water reabsorbed.

On the very bottom of loop of Henle, osmolarity is 1200 mOsM (the biggest).

Ascending: only ions reabsorbed with active pumbing. Creates hyposmotic fluid.

Both water and ions are taken up by countercurrent vasa recta. There is no passive transport because countercurrent has higher or same solute concentration (against concentration gradient).

Question 24

What are the features of nephron secretion?

Answer 24

• H+, K+ and bicarbonate ion are usually secreted to regulate pH and tissue excitability
• uses active transport
• uses non-specific organic anion transporter family. Non-specific means different substrates compete to bind.
• there is also Na+/dicarboxylate contransporter to concentrate bicarbonate ions inside the cell.
• most takes place in the proximal convoluted tubule

Question 25

What are the differences between primary, secondary and teriary active transports and their roles in nephrones?

Answer 25

Primary (antiport): after Na+ was reabsorbed from nephron lumen, sodium-potassium pump uses ATP to keep intracellular Na+ low and release Na+ into medullar interstitial fluid (make highly concentrated medulla). Secondary (symport): Na+/dicarboxylate contransporter (found in both apical and basolateral membrane) Tertiary (antiport): organic anion transporter, uses intracellular bicarbonate ion gradient (found in both apical and basolateral membrane)

Question 26

How glomerulal filtration rate is measured with no invasion?

Answer 26

By determining clearance - rate at which a substance disappears from the body. Inulin is used experimentaly, creatinine clinically. They are freely filtered but not reabsorbed or secreted, so their levels stay the same and hence are reliable.

Question 27

How micturion is controlled?

Answer 27

Stretch receptors in the bladder send signals through sensory neurons to the spinal cord. Internal sphincter passively opens when parasympathetic neurons from the spinal cord fire and cause contraction of bladder smooth muscles. External sphincter opens (relaxes) when motor neurons from the spinal cord stops firing. Brain stem and cortex may further activate or inhibit signals.

Question 28

How water is lost from the body?

Answer 28

Mainly kidneys (1.5 L/day), some in sweat, faeces and lungs (1 L/day). Total = 2.5 L/day How water is obtained into body: water intake (2.2 L/day) + metabolic production (0.3 L/day). Total = also 2.5 L/day

Question 29

Which systems regulate fluid and electrolyte balance?

Answer 29

Rapid, under neural control: respiratory and cardiovascular system. Slow, under endocrine control: renal system.

Question 30

How does vasopressin (antidiuteric hormone) act?

Answer 30

- directly controls water balance - acts on the collecting duct - graded effect: response depends on body's current water and electrolyte concentration - follows circadian pattern: less urine is produced at night 1a) carotid and aortic baroreceprors sense decreased blood pressure 1b) atrial stretch receptors also sence decreased blood volume 1c) hypothalamic osmoreceptors sence osmolarity over 250 mOsM (either due to dehydration or salt intake) 2) triggered specialized hypothalamic neurons produce vasopressin 3) vasopressin is stored in the posterior pituitary and released from here into circulation 4) triggers insertion of aquaporins in the collecting duct and distal convoluted tubule. 5) water reabsorbtion increases to serve body, urine is more concentrated. Alcohol interferes with vasopressin release.

Question 31

How does aldesteone act?

Answer 31

Directly controls sodium balance 1) low blood pressure and high K+ 2) Renin-angiotensin pathway 3) adrenal cortex (zona glomerulosa) produces aldosterone 4) aldosterone acts on P cells of the collecting duct (cytosolic mineralocorticoid receptor) 5) Increased Na+ reabsorbtion and more K+ secretion (insertion of new channels and increasing permeability of the existing ones such as sodium potassium pump).

Question 32

What is renin-angiotensin pathway?

Answer 32

1) Blood pressure drops 2) Juxtaglomerular cells (granular cells) secrete enzyme renin (triggered directly, by increased sympathetic activity and paracrine signals from macula densa) 3) renin converts angiotensinogen (constantly produced by liver) to angiotensin I 4) Angiotensin converting enzyme (from endothelium) converts angiotensin I to angiotensin II 5a) angiotensin II acts on zona glomerulosa of the adrenal cortext to produce aldosterone 5b) angiotensin II is a direct vasocontrictor: binds to receptors in cardiovascular system and leads to smooth muscle contraction. This increases blood pressure. 5c) angiotensin II is directly involved in Na+ reabsorbtion by binding to receptors at various sites of nephron

Question 33

What are the effects of angiotensin II?

Answer 33

- vasoconstriction of arterioles - trigger cardiovascular control in medulla obolongata to increase heart rate - trigger hypothalamus to increase thirst and secrete more vasopressin - trigger adrenal cortex to secrete more aldosterone - directly act on proximal tubule to increase Na+ reabsorbtion

Question 34

What are natriuretic peptides and how they act?

Answer 34

Hormones which promote excretion of Na+ and water (opposite to aldosterone, vasopressin and angiotensin II). 1) myocardium cells stretch due to increased blood volume 2) they release natriuretic peptides 3a) trigger hypothalamus to release less vasopressin 3b) trigger nephron tubules to decrease Na+ reabsorbtion 3c) dilates afferent arteriole to increase glomerulal filtration rate 3d) trigger juxtaglomerular cells to decrease renin production 3e) trigger adrenal cortex to produce less aldosterone 3f) trigger medulla obolongata to relax heart beat 4) all of this decreases blood volume and hence blood pressure

Question 35

What is normal plasma pH?

Answer 35

pH 7.38-7.42

Question 36

How is pH regulated?

Answer 36

1a) too much H+ (too low pH) trigger carotid and aortic chemoreceptors 1b) too much carbon dioxide trigger central chemoreceptors (in brain, so interneurons) 2) activation of respiratory control centre in medulla obolongata 3) activation of motor neurons to increase frequency of contraction of muscles of ventilation 4) increased rate of breathing to breath out more carbon dioxide

Question 37

What are the main buffer systems in the body?

Answer 37

- bicarbonate ions - phosphate - proteins

Question 38

What process is mainly responsible for correcting pH?

Answer 38

Ventilation (breathing) - corrects 75% of disturbances. The rest is done by kidneys (ammonia and phosphate buffers).

Question 39

What is measured in urinalysis?

Answer 39

- specific gravity (high: dehydration or diabetes) - pH (for kidney stones) - glucose (present = diabetes) - bilirubin (too high = liver disease) - ketones (too high = diabetes or starvation) - plasma proteins (too high = kidney damage) - nitrates or nitrites (present = urinary infection) - blood (present = infection or kidney damage) - white blood cells (infection)

Question 40

What are some diseases which can cause kidney damage?

Answer 40

- diabetes mellitus (through diabetic nephropathy) - hypertension - nephritis (kidney inflammation) - polycystic kidney disease - sickle cell anemia - kidney stones

Question 41

What is diabetes insipidus?

Answer 41

Poor secretion or response to vaosopressin. Causes polyuria - too much urine (5-10 L/day instead of 1.5 L/day.

Question 42

Why females are more supseptable to urinary tract infections?

Answer 42

Short urethra (only 5 cm) which is closer to anus. As a result, infections can migrate more easily up to the kidneys and cause very difficult to treat pyelonephritis.

Question 43

What are kidney stones?

Answer 43

- calcium and other ions accumulate and form stones in renal pelvis or ureter - may cause scarring or even kidney failure - too much vitamin D may cause this

Question 44

What are the consequences of chronic kidney failure?

Answer 44

- as a result of glomerulus destruction, glomerulal filtration rate drops and too little urine is produced (oligouria) - progressive destruction of kidney tissue (often due to atherosclerosis of the renal artery) - accumulation of water, sodium and urea leads to hypertension and uremia (acute blood poisoning) - acidosis - hypercalemia - chronic anemia due to disruption in erythroprotein synthesis

Question 45

What are the treatments for kidney failure?

Answer 45

- kidney transplant - dialysis: a) hemodialysis (in hospital 4 hours 3 times a week) b) peritoneal dialysis (portable device at home, everyday, needs permanent catheter)

Question 46

How does dialysis work?

Answer 46

Blood is pumped into the tubes, surrounded with dialysis solution. Blood and dialysis solution are separated with semipermeable membrane. Dialysis fluid is done in the way to resemble normal blood plasma composition. Waste products diffuse away from blood into dialysis solution down concentration gradient. Used dialysis solution is removed and replaced with fresh one.