Block 2 Week 4-5: Renal

Front 1

“How to you tell good pee from bad pee?”

Back 1

1. Depends on what the body needs it to do
2. Think PBL example

Front 2

Demands renal function places on the cardiovascular system

Back 2

8% of resting O2 consumption
25% of cardiac output

Front 3

how long can you survive without kidneys ?

Back 3

days

Front 4

what % of the filtered volume is excreted in the urine?

Back 4

1%

Front 5

Filtration is driven by

Back 5

elevated blood pressure within glomerular capillaries

Front 6

Epithelial ultrastructure of proximal tubule

Back 6

1.Has microvilli
2.Mitochondria scattered throughout

Front 7

what happens to Glucose, amino acids in proximal tubule?

Back 7

100% reabsorbed here

Front 8

Epithelial ultrastructure of thick ascending limb

Back 8

no microvilli
yes mitochondria

Front 9

what does Thick ascending limb do?

Back 9

reabsorbs 25% of solute, but little water
dilutes urine

Front 10

macula densa

Back 10

in thick ascending limb --> Feedback to the juxtaglomerular apparatus (JGA) of its glomerulus of origin (tubuloglomerular feedback

Front 11

Collecting tubules have

Back 11

1) principal cells
2) intercalated cells

Front 12

Principal cells

Back 12

a. Principal cells are essential to regulate the amounts of K +, Na+ and H2O and in the body.
b. Under the control of hormones like aldosterone and ADH.

Front 13

Type I intercalated cells

Back 13

Specialized primarily to secrete acid and reabsorb K

Front 14

Cortical vs. juxtamedullary nephrons

Back 14

Cortical = 80%
juxtamedullary = 20%

Front 15

what does Juxtaglomerular (JG) Apparatus do?

Back 15

mediates feedback from the thick ascending limb to effector cells that regulate glomerular filtration rate and renin release.

Front 16

Podocyte feet (P) embedded in the

Back 16

lamina rara externa

Front 17

The spaces between the interdigitating podocyte feet are called

Back 17

filtration slits

Front 18

filtration slits are bridged by

Back 18

slit diaphragms

Front 19

slit diaphragms are characterized by

Back 19

central dense spot

Front 20

Ultrafiltration

Back 20

basically a more refined filter

filtration through a barrier that excludes molecules of colloidal dimensions (e.g. proteins) but allows small molecules to pass indiscriminately

Front 21

Scaffolding for the filter is made of what?

Back 21

type IV collagen

Front 22

Endothelium and podocytes are so porous that

Back 22

the main filtration barrier is the basement membrane itself.

Front 23

Albumin is unfiltered because

Back 23

of size and negative charge

Front 24

Positively charged molecs of same size =

Back 24

much more filtered (because basement membrane is negative)

Front 25

what is an early sign for glomerular disease?

Back 25

proteinuria

Front 26

Glomerular capillaries are specialized for

Back 26

higher filtration rates than capillaries elsewhere in the body

Front 27

the hydrostatic pressure inside these capillaries is regulated by

Back 27

arterioles at both ends (afferent and efferent)

Front 28

Colloid osmotic pressure (oncotic) gradient

Back 28

Small difference in osmotic pressures and osmolalities of the fluids on the two sides of the glomerular capillary → more colloid (particles) inside capillary --> sucking force drawing fluid into the capillary → counteracts hydrostatic pressure gradient pushing fluid out

Front 29

autoregulation

Back 29

Both renal blood flow (RBF) and GFR remain nearly constant over a range of blood pressures

Front 30

Filtration fraction

Back 30

the fraction of plasma flowing through the kidney that is filtered

Front 31

A selective increase in afferent arteriolar resistance

Back 31

reduces both blood flow and GFR in parallel

Front 32

A selective increase in efferent arteriolar resistance

Back 32

reduces blood flow while increasing GFR

Front 33

Afferent arterioles regulated by

Back 33

1) myogenic
2) adrenergic a-1
3) tubuloglomerular feedback

Front 34

Efferent arterioles regulated by

Back 34

RAAS

Front 35

Angiotensin II is potent

Back 35

vasoconstrictor

Front 36

Angiotensin Converting Enzyme (ACE) inhibitor

Back 36

blocks production of angiotensin II reduces efferent arteriolar tone, and slows progression of renal failure

Front 37

renin pathway

Back 37

renin --> converts angiotensin 1 to 2 --> tells adrenal cortex to secrete aldosterone

Front 38

why do we measure glomerular filtration rate?

Back 38

a. Clinically → early detection of renal disease
b. Physiologically→reference value→compare renal handing of substances

Front 39

what is the gold standard molecule for GFR measurement?

Back 39

inulin

Front 40

why is inulin so good?

Back 40

freely filtered by the glomerulus and is not secreted, reabsorbed or metabolized.

Front 41

formula for GFR =

Back 41

(Uinulin × V) ÷ Pinulin

Front 42

• Creatinine is a by-product of

Back 42

muscle creatine metabolism that is formed and released from muscle at a usually constant rate specific to each individual.

Front 43

Disadvantage of creatinine

Back 43

it is secreted
Creatine overestimates GFR

Front 44

disadvantage of BUN

Back 44

BUN underestimates GFR

• Not constant rate → your liver can break down proteins yielding urea
• Once filtered, urea is passively reabsorbed

Front 45

creatinine concentration↑

Back 45

when GFR↓

Front 46

if GFR drops to 10% of normal

Back 46

creatinine will increase x 10

Front 47

Plasma creatinine concentration is not a sensitive measurement --> how so?

Back 47

GFR can fall by 50-75% before plasma creatinine becomes consistently elevated

Front 48

Elevated plasma urea concentration also suggests

Back 48

reduced GFR

Front 49

pre-renal azotemia

Back 49

BUN elevations not due to renal disease

Front 50

If a substance is freely filtered and then neither reabsorbed nor secreted, its clearance

Back 50

GFR

Front 51

If its clearance is greater than the GFR

Back 51

additional amounts must have been added to the nephron by secretion

Front 52

clearance will be less than GFR

Back 52

If it is freely filtered and then reabsorbed

Front 53

excretion and filtration plots nonlinear

Back 53

active transport

Front 54

linear excretion and filtration plots

Back 54

passive transport

Front 55

filtration left of excretion on plot

Back 55

reabsorption

Front 56

filtration right of excretion on plot

Back 56

secretion

Front 57

Key transport properties of the proximal tubule

Back 57

a. 65-70% of the glomerular filtrate is normally reabsorbed here.
b. The reabsorbate is always isosmotic.
c. This is where sugars, amino acids, metabolic intermediates, etc., are nearly 100% reabsorbed

Front 58

what constitute ~90% of all the solute in the extracellular fluid and in the glomerular filtrate.

Back 58

NaCl and NaHCO3

Front 59

i. Na+ crosses the apical membrane down its very steep electrochem¬ical gradient.
ii. Three classes of proteins mediate its crossing.

Back 59

(1) (a) Na+ channels,
(2) (b) Na+ cotransporters, of many types, for sugars, amino acids, metabolic intermediates and phosphate
(3) (c) the Na+-H+ antiporter. Na+ channels play a minor role. Na+-H+ antiport is quantitatively the most important mechanism.

Front 60

• ~50% of the filtered load of urea

Back 60

urea is reabsorbed passively in the proximal tubule.

Front 61

glomerulotubular balance

Back 61

i. The rate of fluid reabsorption by the proximal tubule is usually a constant percentage of the GFR, 65-70%.

Front 62

Hypervolemia →

Back 62

decreased reabsorption

Front 63

Hypovolemia →

Back 63

increased reabsorption

Front 64

5. Overview of how overall reabsorption is regulated in proximal tubule
a. Mechanisms:

Back 64

i. Autoregulation of GFR in spite of variations in systemic blood pressure.
ii. Tubuloglomerular feedback in each individual nephron
iii. Glomerulotubular balance, when GFR does vary

Front 65

renal function takes how much O2 consumption?

Back 65

8%

Front 66

renal function consumes how much of your cardiac output?

Back 66

25%

Front 67

how much do you excrete per day?

Back 67

1-3 L

Front 68

what % of the plasma entering in the renal artery is filtered across the glomerular capillaries into blind end of the nephron

Back 68

20%

Front 69

what regulates the filtration pressure in each glomerulus

Back 69

the relative resistances of the afferent and efferent arterioles

Front 70

why is albumin unfiltered?

Back 70

large size and negative charge

Front 71

renal autoregulation

Back 71

• Both renal blood flow (RBF) and GFR remain nearly constant over a range of blood pressures

Front 72

RBF is regulated by

Back 72

the sum of the resistances of the afferent and efferent arterioles

Front 73

GFR is primarily determined by

Back 73

Pcap, the hydrostatic pressure in the glomerular capillary

Front 74

what do macula densa cells sense?

Back 74

sense the rate of delivery of NaCl

Front 75

Angiotensin II

Back 75

potent vasoconstrictor --> regulates efferent arteriolar tone

Front 76

Angiotensin Converting Enzyme (ACE) inhibitor in renal failure

Back 76

blocks production of angiotensin II reduces efferent arteriolar tone, and slows progression of renal failure