Statistical modeling in pharmaceutical research and development.
medicine.Kidney lecture 1.(dr.ala)
1. KIDNEY AND URINARY TRACT DISEASE
DR. ALAA HUSSAIN A. AWN
KIDNEY TRANSPLANT NEPHROLOGIST AND
SPECIALIST OF INTERNAL MEDICINE
2. HEADLINES
- ANATOMY AND PHYSIOLOGY (kidneys and UT)
-Ix.
Presenting problems in renal and urinary tract disease.
3. ANATOMY AND PHYSIOLOGY
Adult kidneys are 11-14 cm in
length, located in the
retroperitoneal area on either
side of aorta and IVC.
The right kidney is usually a
few centimeters lower
(because the liver lies above
it) ,,
Each kidney contain
approximately one million
nephrons, which receive rich
blood supply ( 20-25% of
cardiac out put)..
4. NEPHRONS
Which involve;
The glomerulus
(afferent arteriole,
efferent arteriole ,
bowman's capsule)
Proximal convoluted
tubule
Loop of henle
Distal convoluted
tubule
Collecting tubule
5. FUNCTIONS OF THE KIDNEYS
Excretion of nitrogenous waste products and toxins.
Body fluid control.
Electrolyte balance.
Acid – base balance
Endocrine function:
1- erythropoietin production
2- activation of vitamin D
3- renin-angiotensin production
6.
7. large volumes of an ultrafiltrate of plasma (120 ml/min, 170
litres/day) at the glomerulus, and selectively reabsorbing
components of this ultrafiltrate at points along the nephron.
The rates of filtration and reabsorption are under the control of
many hormonal and haemodynamic signals.
8. The kidney is the main source of erythropoietin, which is
produced by interstitial peritubular cells in response to hypoxia.
Replacement of erythropoietin reverses the anaemia of chronic
renal failure .
The kidney is essential for vitamin D metabolism; it hydroxylates
25-hydroxycholecalciferol to the active form, 1,25-
dihydroxycholecalciferol. Failure of this process contributes to
the hypocalcaemia and bone disease of chronic renal failure .
9. Renin is secreted from the juxtaglomerular apparatus in
response to
1- reduced afferent arteriolar pressure,
2-stimulation of sympathetic nerves, and
3- changes in sodium content of fluid in the distal convoluted
tubule at the macula densa.
Renin generates angiotensin II , which causes:
1- aldosterone release from the adrenal cortex,
2- constricts the efferent arteriole of the glomerulus and thereby
increases glomerular filtration pressure .
3- induces systemic vasoconstriction.
By these mechanisms, the kidneys 'defend' circulating blood
volume, blood pressure and glomerular filtration during
circulatory shock. However, the same mechanisms lead to
systemic hypertension in renal ischaemia.
10. MECHANISMS OF MICTURITION AND URINARY CONTINENCE
Continence is dependent on anatomical structures, and on
neurological and muscle (sphincter and detrusor) function.
Parasympathetic nerves arising from S2-4 stimulate detrusor
contraction, resulting in micturition.
Sympathetic nerves arising from T10-L2 relay in the pelvic
ganglia and produce detrusor relaxation and contraction of the
bladder neck (both via α-adrenoceptors).
11.
12. The distal sphincter mechanism is innervated by
somatic motor fibres from sacral segments S2-4 which
reach the sphincter either by the pelvic plexus or via
the pudendal nerves.
Afferent sensory impulses pass to the cerebral cortex,
from where reflex-increased sphincter tone and
associated suppression of detrusor contraction inhibits
micturition until it is appropriate.
These factors operate in a coordinated fashion in the
micturition cycle, which has a 'storage' (or 'filling')
phase and a 'voiding' (or 'micturition') phase .
At approximately 75% bladder capacity there is a
desire to void. Voluntary control is now exerted over
the desire to void, which disappears temporarily.
13. The act of micturition is initiated first by voluntary and then by
reflex relaxation of the pelvic floor and distal sphincter
mechanism, followed by reflex detrusor contraction.
These actions are coordinated by the pontine micturition centre.
14. INVESTIGATION OF RENAL AND URINARY
TRACT DISEASE
TESTS OF FUNCTION
IMAGING TECHNIQUES
OTHER TESTS (Radionuclide studies, renal Bx.)
15. Renal excretory function can be assessed by measuring serum
levels of compounds excreted by the kidney, commonly the
products of protein catabolism (urea and creatinine).
Blood urea is a poor guide to renal excretory function as it
varies with protein intake, liver metabolic capacity and renal
perfusion .
16.
17. Serum creatinine is more reliable as it is produced from muscle
at a constant rate and almost completely filtered at the
glomerulus.
If muscle mass remains constant, changes in creatinine
concentration reflect changes in GFR.
However, an increase outside the normal range is typically not
seen until GFR is reduced by about 50% , and isolated
measurements of serum creatinine may give a misleading
impression of renal function, particularly if muscle mass is
unusually small (or large).
18. Urine measurements to derive creatinine clearance provide a
reasonable approximation of the GFR .
More accurate measurement of GFR is now most easily
undertaken by ascertaining the clearance of 51Cr-labelled
ethylene diamine-tetra acetic acid (EDTA).
19. The blood filtered through the glomerulus in a rate of
90-120 cc/min.( 170 L / day)
We use the creatinine clearance as approximation of
glomerular filtration rate.
Creatinine clearance= ( 140-age) wt / (s. creatinine )(
72)
Creatinine clearance in Female=___________* 0.85
Cr cl =U Cr * v / S Cr * Time ( min)
21. URINALYSIS
Dipsticks may be used to screen for blood and protein semi-
quantitatively .
Urine microscopy can detect
red cells of glomerular origin and red cell casts, indicative of
intrinsic renal disease,
white blood cells and bacteria seen in urine infections.
Crystals (e.g. of calcium oxalate, cysteine or urate) may be
seen in renal calculus disease, although calcium oxalate and
urate crystals are also sometimes found in normal urine that has
been left to stand.
Urine pH can provide diagnostic information in the assessment
of renal tubular acidosis
persistently low specific gravity will be found in diabetes
insipidus .
22. SHOWING ON THE RIGHT GLOMERULAR BLEEDING WITH MANY
DYSMORPHIC FORMS INCLUDING ACANTHOCYTES (TEARDROP
FORMS), AND ON THE LEFT BLEEDING FROM LOWER IN THE
URINARY TRACT
23. ,ON THE LEFT, PHASE CONTRAST IMAGES SHOW HYALINE
CASTS, A NORMAL FEATURE OF URINE (× 160). ON THE RIGHT,
NUMEROUS RED CELLS AND A LARGE RED CELL CAST IN ACUTE
GLOMERULAR INFLAMMATION (× 100, NOT PHASE CONTRAST
24. Timed urine collections can be used;( 24 h)
To measure creatinine clearance as a surrogate for GFR
can provide a quantitative measure of urinary protein loss.
measure the urinary excretion rates of compounds such as
calcium, oxalate and urate that can form renal calculi .
25. Simple measurement of tubular excretory function can be made
by comparison of blood and urine ratios of electrolytes to
creatinine.
Fractional excretion of sodium (= urinary Na/plasma Na ×
plasma creatinine/urine creatinine).
It is reduced in volume depletion when the tubules are avidly
conserving sodium, and increased in the tubular damage
associated with acute tubular necrosis.
26. IMAGING TECHNIQUES
Plain X-rays ( KUB)
may show the renal outlines ,
opaque calculi and calcification within the renal
tract.