Functional microanatomy of the kidney

Question 1

What is physiology?

Answer 1

Physiology is the study of how individual organ systems within the body function, and how such individual functions integrate so as to allow the animal to adapt to a changing internal or external environment.

Question 2

What is the main function of the kidney?

Answer 2

Maintain homeostasis

Question 3

What is homeostasis?

Answer 3

The tendency to maintain relative constancy of physiological variables (i.e. internal stability) despite large external fluctuations

Question 4

What did Galen wrote about urine before the 200s.

Answer 4

“the amount of urine every day shows clearly that it is the whole of the fluid drunk which becomes urine, except that which comes away with the dejections or passes off as sweat or insensible perspiration. This is most easily recognized in winter in those who are doing no work but are carousing, especially if the urine be thin and diffusible; these people rapidly pass almost the same quantity as they drink.”

Question 5

What did Claude Bernard famously say?

Answer 5

Claude Bernard (18th century physiologist) « La fixité du milieu intérieur est la condition de la vie libre ».

Question 6

Name the 3 characteristics of kidneys as an organ

Answer 6

The kidney is an organ that is:

• Regulatory
• Excretory
• Endocrine

Question 7

Name the 6 characteristics of homeostasis

Answer 7

1. Steady state
2. Set-point
3. Negative feedback
4. Positive feedback
5. Error signal
6. Physiological range

Question 8

What are the advantages of being multicellular?

Answer 8

Division of labour between different cell types
 Unicellular organisms have one cell do everything (take in nutrients, metabolize them, excretes wastes… –> less opportunity for specialized function; e.g. neurons sending info from one region to another)
 Specialized cells usually require a specific and constant set of conditions (e.g. solute and ion concentration is different inside vs outside cells)
• E.g. neurons need gradient for excitability and action potential, need high Na and K
- BUT… Requires body fluids that have a stable composition and osmolality

Question 9

What are 2 strategies to maintain gradient against outside environments?

Answer 9

o Minimize gradient – (e.g. sharks taste like urea +++ because sharks use urea as an osmolyte to counterbalance the high osmolality of seawater. They have similar plasma Na and Cl to us but yet they need to live in very high NaCl concentration. They minimize the gradient with urea.)
o Lower permeability (barrier between outside and outside low leakage)

Question 10

Name 4 examples of animals living in aquatic environments that have adapted to maintain salt gradient.

Answer 10

 E.g. sharks taste like urea +++ because sharks use urea as an osmolyte to counterbalance the high osmolality of seawater. They have similar plasma Na and Cl to us but yet they need to live in very high NaCl concentration. They minimize the gradient with urea.
 E.g. Ionic strength very low in freshwater – have special mechanism to uptake Na and Cl from environment, otherwise they would deplete.
 E.g. Brine shrimps drink large amounts of surrounding fluids and have a salt gland that allows them to secrete salt with active transporters (“purification system”)
 E.g. saline mosquito larvae have a tubule structure (similar to kidney) that actively secretes K, Cl, Mg and SO4 in the tubule, connected to gut, then further modified. This makes them be able to live in very salty and/or very alkaline conditions.

Question 11

Name an advantage of being terrestrial

Answer 11

More availability of oxygen (< 1% in water)

Question 12

Name a disadvantage of being terrestrial. How do animals do to prevent dehydration in dry environments?

Answer 12

More possible dehydration

 E.g. Waxy monkey frogs live far away from water in hot environments; conserves water by increasing barrier function of skin (have glands that secrete waxy substance to cover surface – prevents evaporation) – increase resistance to evaporation
 E.g. water-holding frog (Australia) lives in desert – behavioural strategy (stands in cooler areas away from sun to prevent evaporation) but also have a bladder that makes up 1/3 of BW; use it as a water tank and supply to maintain equilibrium
 E.g. kangaroo rats never drink water, thus their water comes from the food (metabolize CHO  CO2 + H2O) = main water supply (90% comes from metabolism and 10% only from the actual moisture in food). Losses only 25% renal and 70% respiratory and 5% feces. Have VERY long loops of henle (inner medulla) for water conservation.
 E.g. beaver kidneys have very short nephrons and no inner medulla. Only outer medulla and a huge cortex. Beavers never have to conserve water because they live in freshwater. Thus, doesn’t need loops of henle for water conservation and concentration of urine.
 E.g. rabbits have a mix of long and short loops (like humans) – short loops clean the blood.

Question 13

Name strategies to maintain ionic and osmotic gradients

Answer 13

many strategies are used to maintain ionic and osmotic gradients including reduced permeability of epithelial surfaces, specialized excretory organs and secretory glands, behavioural and other adaptations

Question 14

Name 3 functions of the kidney

Answer 14

Regulation/Homeostasis
Excretion
Exocrine

Question 15

Name 6 things that the kidneys regulate to maintain homeostasis

Answer 15

a. ECF volume – maintain perfusion to the brain
b. ECF osmolality
c. Composition of body fluids
d. Blood pressure (linked to ECF volume)
e. RBC mass – through effect on EPO
f. Skeletal integrity – through calcium regulation

Question 16

Name 3 ways in which kidneys maintain the composition of body fluids

Answer 16

i. Acid-base status (effect on bicarbonate transport)
ii. ECF K+ concentration (very tight regulation) – secretion of potassium by distal tubule
iii. Divalent ion concentration (Ca, Mg, …)

Question 17

What do kidneys excrete? (4)

Answer 17

a. Nitrogenous wastes – toxic if not excreted
b. Dietary end products
c. Drugs and drug metabolites
d. Products of metabolism

Question 18

Name 3 hormones secreted by the kidneys

Answer 18

a. Erythropoietin (EPO) – stimulates bone marrow
b. 1,25-OH Vitamin D – active form of VD
c. Renin – catalyzes formation of angiotensin I in RAAS

Question 19

Which other compounds do kidneys synthesize?

Answer 19

The kidneys are also important sites of metabolism, synthesizing important compounds such as ammonia from glutamine and, under some circumstances, glucose from lactate.

Question 20

What is the kidney covered by?

Answer 20

The kidney is covered by a fibrous capsule (protective fibrous material)

Question 21

What connects the kidey to the ureter?

Answer 21

renal pelvis

Question 22

What is the spot at which the renal artery, vein and pelvis join the kidney.?

Answer 22

The hilus

Question 23

What connects the kidney and the bladder?

Answer 23

The ureter

Question 24

Name the 3 major regions of the kidneys and their sub-regions.

Answer 24

1) the cortex,
2) the medulla (pyramid) which consists of the
a. “outer medulla”, which is made up of the “outer stripe” and “inner stripe”, and
b. “inner medulla”, which includes the papillary region
3) the calyces and pelvis, which connect with the ureter

Question 25

How many pyramids do rats have? Humans?

Answer 25

Rats have 1 pyramid, humans have ~ 12 pyramids

Question 26

What is a pyramid?

Answer 26

The structure of the pyramid is similar in all species.
Cortex (outer portion) –> outer medulla –> inner medulla –> papilla –> All connected by minor calyces (in humans and other animals that have multiple pyramids) – tubes that collect fluid from apex of pyramids –> major calyces –> renal pelvis

Renal tubules empty at the tip of the pyramids.

Question 27

Which parts of the kidneys contain smooth muscles and what are their functions?

Answer 27

The walls of the calyces, pelvis and ureter contain smooth muscle. Peristaltic contractions help drive urine into and through the ureter; and may also cause some “reflux” of putative urine over the epithelium that lines the surface of the papilla, where further reabsorption can take place. Such post-nephron modifications of the urine may be important, particularly during diuresis

Question 28

How many nephrons feed in 1 collecting duct?

Answer 28

6-8

Question 29

In what part of the kidney are the glomeruli located?

Answer 29

Glomeruli are all in the cortex

Question 30

Which blood goes to the vasorecta?

Answer 30

Blood flow comes in cortex, then small portion goes to vasorecta

Question 31

Where does the blood coming to the kidney go?

Answer 31

20% of the blood (plasma) is filtered –> glomerulus to tubule –> modified then excreted
80% rest goes either to vasorecta or peritubular capillaries (wrap around renal tubule) – exchange of solutes and fluid.

Question 32

Name the different parts of the kidney tubule in order

Answer 32

1. Glomerulus
2. Proximal convoluted tubule
3. Thin descending limb (Loop of henle)
4. Thin ascending limb (Loop of henle)
5. Thick ascending limb (Loop of henle)
6. Distal convoluted tubule
7. Collecting duct

Question 33

What is the functional unit of the kidney?

Answer 33

The nephron (aka renal tubule)

Question 34

How many nephrons does a human kidney have?

Answer 34

The human kidney contains about 1.2 million nephrons.

Question 35

How many different cell types does a nephron have?

Answer 35

• Individual nephrons consist of more than 10 cell types which form an epithelial layer.

Question 36

Name the 5 main portions of the renal tubule, their sub-portions and their functions

Answer 36

1) Glomerulus
- capillary tuft
- Bowman’s capsule (function: ultrafiltration of large volumes of fluid, 180 L/day)

2) Proximal tubule
- convoluted part (early or “S1”, and late or “S2”)
- straight part (S3 or pars recta)
(function: reabsorption of most of the filtrate Na, K, Cl, urea, glucose, amino acids, acidification, secretion of organic acids and bases).

3) Loop of Henle
- thin descending limb
- thin ascending limb
- thick ascending limb (medullary “mTAL” and cortical “cTAL”)
(function: dilutes urine and produces an osmotic driving force in the interstitium, which ultimately allows the concentration of the urine).

4) Distal tubule
- convoluted part (early and late)
- connecting part (functions: fine regulation of sodium, potassium, Ca2+ and PO43- excretion; dilutes the urine).

5) collecting duct - cortical part (CCD)
- medullary part (outer and inner parts; OMCD & IMCD, respectively)
(function: important site of regulated Na+
absorption, K+ and H+ secretion, and is the site where osmotic concentration of the final urine takes place).

Question 37

What is the difference between nephrons that are closer to the surface of the kidney (superficial) and those that are closer to the medulla (juxtamedullary)? What is the proportion of one type to the other in humans?

Answer 37

There is heterogeneity between nephrons according to whether the glomerulus is situated near the surface of the kidney (superficial) or near the junction of the cortex and medulla (juxtamedullary). In humans, about 90% of nephrons are superficial.

Superficial nephrons (vs. juxtamedullary) have…

• Smaller glomeruli
• Shorter loops of Henle
• Lower single nephron glomerular filtration rate (SNGFR).
• Juxtaglomerular nephron’s efferent arterioles tend to form vasorecta vs. peritubular capillaries

There is also heterogeneity of cell type within each segment; that is, cells having very different ultrastructures and transport activities are often interspersed within in one segment.

Question 38

True or false: Afferent arterioles (Af) are larger than efferent arterioles (EF)

Answer 38

true

Question 39

Explain the presence of podocytes on the outside of the capillaries of the glomerulus

Answer 39

Around the outside of the capillaries, there are podocytes (visceral epithelial cells that cover the outside of the capillaries)
They wrap around the outside of the capillaries and their foot processes form a “zipper” around the outside of capillaries.
Between each interdigitation, there is a membrane with a slit diaphragm – pore that allows fluid to go through and prevents large molecules to go through.