L 2: Logic of Kidney

Question 1

8 functions of the kidney

Answer 1

-elimination of N waste products -regulate body fluid content -regulate body fluid composition -regulate BP -regulate Acid/Base balance -regulate RBC volume (Epo) -regulate Calcium (bone) metabolism -eliminate and metabolize endo and exo active mlcs

Question 2

2 types of nephrons

Answer 2

1. superficial: 85%; short loops that extent just to the boundary between the outer and inner medulla 2. Juxtamedullary: 15%; longer loops that extent as far as the tip of the medulla. Urine concentration!!

Question 3

First part of the nephron is the _____. What is its function?

Answer 3

-glomerulus: cluster of capillaries in which the process of filtration of blood occurs

Question 4

2 main pathways for excretion in the kidney

Answer 4

-filtered by G (potentially reabsorbed) -secreted

Question 5

An afferent arteriole brings blood into the glomerulus, where filtration occurs across the capillary segment. Where does the blood and filtrate go?

Answer 5

-filtrate goes into Bowman’s capsule and then flows into proximal convoluted tubule where much of the filtrate (water, ions, glucose, AAs) are reabsorbed -blood returns back to circulation via efferent arteriole

Question 6

The logic of renal handling of toxins

Answer 6

-filter the blood over and over again all day long to eliminate breakdown products of protein metabolism and selective reabsorb what we want

Question 7

Normal filtration rate of 2 kidneys

Answer 7

-180 L/day: lots of reserve to account for diet changes, etc!

Question 8

3 components of Glomerular filtration Pressure

Answer 8

1. GCP: glom. cap pressure: favor filtration
2. COP: colloid osmotic P: oppose F; as plasma moves along the G cap, the removal of water increases conc of protein which = inc in COP
3. capsule pressure (CP): oppose F

Question 9

What is the ultimate role of glomerular filtration?

Answer 9

• elimination of N waste products: mostly as urea and some as uric acid
• ammonia via liver plays a small role

Question 10

Autoregulation of renal blood flow and how is it achieved?

Answer 10

• able to keep a relatively level GFR over a change in renal arterial P
• if MAP drops too low, GFR stops and so does urine production
• as MAP inc afferent R increases to shield capillaries; when MAP falls, afferents dilate and the efferents constrict (inc R); Juxaglomerular apparatus

Question 11

Components of the Juxaglomerular apparatus

Answer 11

• JG cells
• mesangial cells
• macula densa

Question 12

Logic of tubular transport

Answer 12

• reabsorb all the constituents of filtrate except for end products of metabolism, and any constituent of body fluids not needed for homeostasis (water, electrolytes)
• secrete across the tubule certain constituents such as drugs, particularly if protein (albumin) bound
• only major exception is potassium which is mostly secreted

Question 13

3 control systems for maintaining homeostasis

Answer 13

• physical forces: BP and renal BF
• hormonal regulation
• autocoids
• fish and people adapt to huge variability in mineral and fluid intake in a way that preserves the milieu interior. this process is modulated by local physical factors (hydrostatic, oncotic P) and hormones which influence epithelial differentiation, transporter function, and metabolism

Question 14

What is the normal level of Na excretion by the kidneys?

Answer 14

• it depends!!! depends on the intake!
• when you suddenly intake more Na, you body takes 3-5 days to correct this and increase its output to match the input. So some Na is accumulate which water will follow and thus a slight weight gain is experienced. A new, higher-steady state will be established. If Na intake suddenly drops, it will take a while to reduce one’s output and thus weight will be lost.

Question 15

Mode of proximal tubular transport of solutes and water

Answer 15

• very leak epithelium transports solutes actively across the cell compartment (makes lumen slightly dilute)
• water reabsoprtion is passively via osmosis and can be para or trans cellularly

Question 16

Proximal tubule organization and logic

Answer 16

• a “leaky” epithelium that reabsorbs high volumes of fluids and tubular fluid constituents, has small transepithelial electrical potntial, maintains small gradients, has high water permeability
• logic: process the huge filtration rate BULK RECLAMATION of most small mlcs (ions, water) and selective large mlcs via receptors (leaked albumin). Large toxins delivered downstream

Question 17

Mechanism of solute transport in proximal tubule

Answer 17

• main driving force is the gradient for sodium from the lumen to the cell interior. Cell interior Na levels are kept low by a basolateral Na/K ATPase
  1. Na enters cell through open channels, moving down the electrochemical gradient
  2. Na is pumped out of the basolateral side of cell by Na/K ATPase
• Na uptake also helps drive cotransport of other mlcs like glucose and AAs

Question 18

Distal Nephron transport

Answer 18

• “tight” epithelium that is mostly under hormonal control, is able to establish steep gradients, has a high electrochemical gradient, is generally water impermeant, and provides FINE regulation of final urinary excretion.
• it is amenable to hormonal regulation, so here is where creation of the steady state balance occurs

Question 19

Overall plan of nephron transport

Answer 19

Question 20

Liddle’s Syndrome

Answer 20

In Liddle’s syndrome, a rare hereditary syndrome affecting, the sodium channel,
ENaC is “stuck” open and inordinate amount of time. This leads to inappropriately high rates of sodium uptake in the distal nephron, well
beyond the needs of the body. This in turn expands the blood and extracellular fluid volumes and raises blood pressure through a volumebased
mechanism. It is data from experiments of nature like this that have led to the concern about the impact of dietary sodium even in normals.

An example of HTN due to extracellular fluid volume

Question 21

renal control of BP through vasoconstrictive mechanisms

Answer 21

-RAAS system: AngII via renin release

Question 22

Summarize the 2 main ways MAP is affected and how the kidney functions in both of these ways

Answer 22

1. Blood volume: Na reabsorption and water follows
2. Vasoconstriction (vascular resistance): Ang II via RAAS

Question 23

Kidney and Acid Base regulation

Answer 23

• H+ ion has special significant because of the narrow ranges it must be maintained in order to be compatible with living systems (pH drop= coma, pH too high=cramps)
• lungs help and regulate CO2 production
• Kidney excretes H+ and also produces alkali substances

Question 24

4 sources of Hydrogen ions

Answer 24

1. cell metabolism (CO2)
2. food products: proteins
3. medications
4. metabolic intermediate by-products

Question 25

Kidneys responst to acidosis or alkalosis

Answer 25

• kidney compensates for acid-base imbalance within 24 hours and is responsible for long term control
• acidosis: retains bicarb ions and eliminate H+ ions
• alkalosis: eliminates Bicarb ions and retains H+

Question 26

Kidney as an endocrine organ

Answer 26

• regulates VitD synthesis, regulated by PTH
• 25-OH D3 from liver in proximal tubules can be made active (1,25-OH2D3) or inactive

Question 27

Role of kidney in regulating Red cell mass

Answer 27

-kidney has O2 sensors what when hypoxic, secrete Epo

Question 28

T/F: kidney has many enzymes involved in renal metabolism of drugs

Answer 28

-true