Gilberts: Renal Function
Ruth Olson
Kidney functions
•
Excretion of metabolic waste products:urea,
creatinine, bilirubin, hydrogen
•
Excretion of foreign chemicals:drugs, toxins,
pesticides, food additives
•
Secretion, metabolism, and excretion of
hormones
- renal erythropoetic factor (EPO)
- 1,25 dihydroxycholecalciferol (Vitamin D).
Patients with renal failure often present with
anemia and vit. D deficiency.
- renin
•
Regulation of acid-base balance
•
Whole body metabolism  Gluconeogenesis:
glucose synthesis from amino acids
•
Control of arterial pressure
•
Regulation of water & electrolyte excretion
•
He gave us numbers NOT for recall on the
examination but to give you an idea of what the
health burden of hypertension and renal disease
is on Minnesota and the United States. LOTS OF
PEOPLE HAVE IT AND ITS EXPENSIVE!!! It should
be obvious that YOU are going to treat patients
with these disorders.
•
Endstage renal disease has increased
4x in last 25 years.
•
Blacks and Native Am. Have highest
rates of ESRD
•
ESRD is increasing so much because of
increases in diabetes and hypertension
•
Excess weight gain and maintenance is
dangerous causes >90% diabetes
and 64-75% HTN. Over 70% of ESRD is
from hypertension and diabetes.
Hypertension and obesity should be
treated aggressively to minimize or
prevent ESRD
•
Babies at very low and very large end
of the birth rate spectrum have a
higher rate of chronic disease. Ex.
Kidneys: 2 of them. The major
portions (macroscopically
speaking) are the cortex,
medulla, artery, vein, ureter,
pelvis and the hilum when it all
comes out in the middle.
When we think about the
kidneys we often think of them
as being like little garbage
disposals. This is because the
kidneys are important in
removing waste products and
metabolites from the blood
and the body. But it is not just
junk and crud that the kidneys
get rid of. Things like insulin are
cleared by the kidney. This is an
important example  if you
have a patient that is diabetic
and has renal failure you have
to keep in mind how the kidney
regulates and excretes insulin
so that you do not overdose
the patient on insulin.
The efferent arteriole is unique;
usually it’s a vein leaving. Vasorecta:
deep part in medulla or whole thing
yellow part is the tubule. Yellow
urine. Redox Blue: deox
Gilberts: Renal Function
Ruth Olson
Pima tribe, Aboriginese, UK, US.
Prenatal care is important in long term
health
•
Kidney is fully formed but not fully
functional at the time of birth
Mean arterial pressure (mmHg)
Early nephron deficit and HTN: HTN damages nephrons
130
120
110
100
90

Excretion = Filtration –Reabsorption +
Secretion

Filtration : somewhat variable, not
selective (except for proteins; also
things bound to praren’t filtered
either), avg 20% of renal flow

Reabsorption : highly variable and
selective. Most electrolytes (e.g. Na+,
K+, Cl-) and nutritional substances (e.g.
glucose) are almost completely
reabsorbed; most waste products (e.g.
urea)poorly reabsorbed

Secretion : highly variable; important
for rapidly excreting some waste
products (e.g. H+), foreign substances
(including drugs), and toxins
80
70
60
500
550
600
650
700
750
3
Glomerulus number (x10 )

Nephron # decreases as we age. After 40,
10% loss for every ten years. Nephron loss
is accelerated in uncontrolled diabetic and
hypertensive patients, leading to renal
disease.
Drugs are removed by filtration and excretion
Here we have diagrammed the 3 steps to urine
formation. 1 GFR (filtration: goes on at glomerular
capillaries), 2, tubular reab (tubule peritubular
capillaries) sorption which as about 99% of all solutes
(Na, CL, glucose, Amino acids) then tubular secretion
(tubular capillaries  tubule.)
180 L per day filtered. About 99% of filtrate is absorbed
into peritubular capillaries.
Creatinine: important clinical indicator of renal
function: filtered and excreted.
Steady state in physiology: ex. If you go on a high salt
diet, excretion will increase to get rid of extra Na2+
Gilberts: Renal Function
Ruth Olson
Glomerular Filtration Rate (the essence of kidney
function) = 125 ml/min =180 L/day




Plasma volume is filtered 60 times per day. This
allows are body to regulate things more
Glomerular filtrate composition is about the
same as plasma, except for large proteins
Filtration fraction (GFR / Renal Plasma Flow) =
0.2 (i.e. 20% of plasma is filtered)
There is a flomerular capillary filtration barrier
(which is neg. charged.)
•
assessment and monitoring of known renal
disease
•
Eating lots of protein also increases GFR, but that
is a transient effect.
•
“Is the dipstick OK?” : dipstick protein tests may
not be very accurate: “trace” results can be
normal & positives must be confirmed by
quantitative laboratory test.
Microalbuminuria
•
Effects of size and charge on filterability
Definition: urine excretion of > 30 but < 150 mg
albumin per day
• Causes: early diabetes, hypertension, glomerular
hyperfiltration
• Prognostic Value: diabetic patients
withmicroalbuminuria are 10-20 fold morelikely
to develop persistent proteinuria
Things that are polycationic filter MUCH better
than anionic things, reguardless of size.
There are rare conditions where basement
membrane loses its charge; this doesn’t show up
with histological evaluation!
Clinical importance of Proteinuria
•
early detection of renal disease in at-risk
patients
•
hypertension: hypertensive renal
disease
•
diabetes: diabetic nephropathy
•
pregnancy: gestational proteinuric
hypertension (pre-eclampsia)
•
annual “check-up”: renal disease can
be silent
Bowman’s capsule colloid osmotic pressure is
usually zero. Net filtration is normally 10 mmHg.
The importance of the values: this is much higher
than you have in normal capillary beds. You don’t
want that in your skeletal muscle  that’s edema.
Normal Values:
GFR = 125 ml/min
Net Filt. Press = 10 mmHg
Kf = 12.5 ml/min per mmHg, or 4.2 ml/min per
mmHg/ 100gm (400 x greater than in most tissues)
Gilberts: Renal Function
Ruth Olson



This is only about 8 weeks of obesity. This is
reversible in dogs if weight loss is achieved. BM
gets much more thick in obesity.
Dogs respond to diet the same way we do.
When they go on a low fat diet, the
hyperfiltration stops.
Autoregulation: In other places: match delivery and
demand at local tissue sights. In kidney, there is far more
delivery of nutrients than needed for renal metabolism.
Autoregulation here is more about helping regulate renal
function and excretion of what you want to get rid of. In
kidney disease, there is a loss of the ability to
autoregulate. This is why renal disease is a slippery slope;
progression is dangerous and prevents autoregulation. No
autoregulation of urine flow.
Gilberts: Renal Function
Ruth Olson
Both of these are mediated by a hormone acting on
smooth muscle.
Normally sympathetic activation does not have an effect
on GFR, but it does in situations like hemorrhage.
2. Also important in HTN: ACE inhibitors are percribed
which prevents AT II formation. If a person already has a
deterioration in renal function it can be problematic
blocking AT II formation.
Pgs, in particular, Prostacyclin(PC) is a VD. It will inc GFR
and BF. If you block PC, the opposite can happen. NSAIDs
can cause severe decreases in GFR in patients with
cirrhosis (as indicated by creatine clearance.)
Gilberts: Renal Function
Ruth Olson
RENAL AUTOREGULARION: On top: RAP: steady state:
100. Place a clamp on renal artery: BP dec to 80. Also,
dec in GRF (acute). RAP remains at 80, but because of
autoregulatory mechanisms, GFR and Bf will recover back
to normal.
If you increase BP to kidney, inc GFR and BF (acute) but
autoregulatory mechanisms will cause them to recover.
Fxns of renal BF
•
Structure of the juxtaglomerular apparatus: Macula
Densa:


Tubular-glomerular feedback: Involves delivery
of Na2+ to distal tubules.
The macula densa measure Na2+ delivery (not
Na2+ concentration) in the distal tubule (we
don’t know how.)
To deliver enough plasma to kidneys for
glomerular filtration
•
To deliver nutrients to kidney so that the
renal cells can perform their functions
(only about 20% of renal blood flow
needed for this function)
Ang II blocade impairs GFR autoregulation: you need a
higher arterial P to get a given GFR.
Gilberts: Renal Function
Ruth Olson
Questions:
1.
12. T/F The macula densa measures Na2+
concentration in the distal tubule
Creatinine undergoes
a. Filtration
b. Filtration and complete reabsorption
c. Filtration and partial reabsorption
d. Filtration and secretion
2.
Inulin undergoes
a. Filtration
b. Filtration and complete reabsorption
c. Filtration and partial reabsorption
d. Filtration and secretion
3. Glucose undergoes
a. Filtration
b. Filtration and complete reabsorption
c. Filtration and partial reabsorption
d. Filtration and secretion
4. Sodium chloride undergoes
a. Filtration
b. Filtration and complete reabsorption
c. Filtration and partial reabsorption
d. Filtration and secretion
5. Amino acids undergo
a. Filtration
b. Filtration and complete reabsorption
c. Filtration and partial reabsorption
d. Filtration and secretion
6. Organic acids and bases undergoe
a. Filtration
b. Filtration and complete reabsorption
c. Filtration and partial reabsorption
d. Filtration and secretion
7. Which races have the highest rates of ESRD
a. Whites
b. Native Americans
c. Asian Americans
d. Blacks
8. T/F All nephron loss is due to aging
9. What are causes of microalbuminuria?
a. early diabetes,
b. hypertension
c.
glomerular hyperfiltration
d. All of the above
10. In what special case does sympathetic
activation have an effect on GFR?
11. Fill in the chart below:
Answers
1. a
7.b, d
2.a
8.F
3. c
9. D
4.b
5.c
10.Hemorrhage
6.d
11.
12. F. The macula densa measures Na2+ delivery, NOT
Na2+ concentration