Lecture 2

The Urine
Volume and composition
The volume and composition of normal urine vary widely from day to day, even in healthy individuals,
as a result of food and fluid intake and of fluid loss through other channels as affected by
environmental conditions and exercise. The daily volume averages 1.5 litres (about 1.6 quarts) with a
range of 1–2.5 litres, but after copious sweating it may fall as low as 500 millilitres, and after excess
fluid intake it may reach three litres or more. There is also variation within a 24-hour period. Excretion
is reduced in the early hours, maximal during the first
few hours after rising, with peaks after meals and Some urine constituents
during the early stages of exertion. The urine (g/24 hours)
produced between morning and evening is two to four
times the night volume. The excessive secretion of urea 25–30
urine (polyuria) of chronic renal disease is typically uric acid 0.6–0.7
nocturnal.
The volume of urine is regulated to keep plasma
creatinine 1.0–1.2
osmotic concentration constant, to control the total hippuric acid 0.7
water content of the tissues, and to provide a vehicle ammonia 0.7
for the daily excretion to the exterior of some 50 grams amino acids 3
of solids, mostly urea and sodium chloride. In a man sodium 1–5 (NaCl 15.0)
who ingests 100 grams of protein and 10 grams of salt
daily, the urine will contain 30 grams of urea and 10 potassium 2–4
grams of salt; there are many other possible calcium 0.2–0.3
constituents, but they amount to less than 10 grams magnesium 0.1
overall. chloride 7
phosphate 1.7–2.5
Oliguria - a diminished capacity to form and pass
urine-less than 400 mL in every 24 hours-so that the sulfate 1.8–2.5
end products of metabolism cannot be excreted efficiently. It is usually caused by imbalances in body
fluids and electrolytes, renal lesions, or urinary tract obstruction. Also called oliguresis.

Anuria - sometimes called anuresis, is nonpassage of urine,[1] in practice is defined as passage of

less than 100[2] milliliters of urine in a day.[3] Anuria is often caused by failure in the function
of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It
may occur with end stage renal disease.

Poliuria - is excessive or an abnormally large production or passage of urine (greater than 2.5[5] or
3[6] L over 24 hours in adults). Frequent urination is usually an accompanying symptom. Increased
production and passage of urine may also be termed diuresis.[7][8] Polyuria often appears in
conjunction with polydipsia (increased thirst), though it is possible to have one without the other, and
the latter may be a cause or an effect.

Nocturia – excessive urination at night. The two primary causes of nocturia are hormone
imbalances and vesical problems. It is also tied to circadian biology.

1
Some urinary constituents (Table 3)—the products of metabolism of nitrogenous substances obtained
from food—vary widely in relation to the composition of the diet; thus the excretion of urea and sulfate
is dependent on the diet-protein content. A high-protein diet may yield a 24-hour output of 17 grams
of nitrogen, a low-protein diet of the same calorific value only three to four grams.

Normal urine constituents: water – 95%, nitrogen containing substaces: Urea – 2%, creatinin,
ammonia and uric acid – 0,2%, some of electrolyts: Na+, K+, Ca2+, H+ - ions.

The urine is normally clear. It may be turbid from calcium phosphate, which clears if acetic acid is
added. Microscopic deposits include occasional casts, vaguely resembling in form the renal tubules
from whose lining they have been shed. An ammoniacal smell is the result of decomposition of urea
to ammonia by bacteria and is commonly present on babies’ diapers. Certain foods and drugs may
cause distinctive odours. The colour of urine depends on its concentration but is normally a bright
clear yellow from the pigment urochrome, an end product of protein metabolism. There are also
traces of other pigments: urobilin and uroerythrin. The colour may be influenced as well by vitamins,
food dyes, beetroot, and certain drugs.

The specific gravity of urine may vary between 1.001 and 1.04 but is usually 1.01–1.025. Such
variation is normal, and a fixed low specific gravity is an indication of chronic renal disease. If fluid
intake is stopped for 24 hours, a normal kidney will secrete urine with a specific gravity of at least
1.025. There is a limit to the concentrating powers of the kidney, so that the urine is rarely more than
four times as concentrated as plasma. In order to excrete their normal solute load, the kidneys need a
minimum water output of 850 millilitres as a vehicle; this volume is often called the minimum
obligatory volume of urine. If this is not available from intake it has to be withdrawn from the tissues,
causing dehydration; but the usual intake is well above the minimum and the urine is rarely at its
maximum possible concentration. The reaction of the urine is usually acid, with an overall range of pH
4 to 8 (lemon pie has a pH of 2.3; the value 8 is slightly alkaline, about equal to the pH of a 1 percent
solution of sodium bicarbonate).

Foreign proteins of molecular weight less than 68,000 are excreted in the urine, while those of the
plasma are retained in the body. If, however, the kidneys are damaged by disease or toxins, the
glomeruli will transmit some of the normal serum albumin and globulin and the urine will coagulate on
warming. Normally, the urine contains only very small amounts of protein (less than 50 milligrams per
24 hours); however, protein content in the urine is increased after exercise, in pregnancy, and in
some persons when standing (orthostatic albuminuria). The protein loss may be greatly increased in
certain chronic renal diseases; in the nephrotic syndrome it may even reach 50 grams in a 24-hour
period. Certain specific and easily identifiable proteins appear in the urine in diseases associated with
the overgrowth of cells that make immunoglobulins.
Glucose is found in the urine in diabetes mellitus. In some healthy persons, however, there may also
be an abnormal amount of glucose in the urine because of a low threshold for tubular reabsorption,
without any disturbance of glucose metabolism. Lactosuria (abnormal amount of lactose in the urine)
may occur in nursing mothers. Ketone bodies (acetone, acetoacetic acid) are present in traces in
normal urine but in quantity in severe untreated diabetes and in relative or actual carbohydrate
starvation; e.g., in a person on a high-fat diet.
The urine may contain hemoglobin or its derivatives after hemolysis (liberation of hemoglobin from
red blood cells), after incompatible blood transfusion, and in malignant malaria (blackwater fever).
Fresh blood may derive from bleeding in the urinary tract. Bile salts and pigments are increased in
jaundice, particularly the obstructive variety; urobilin is greatly increased in certain diseases such as
cirrhosis of the liver.

2
Porphyrins are normally present only in minute amounts but may be increased in congenital
porphyria, a disease characterized by sensitivity to sunlight or by insanity. The presence of porphyrins
also may increase after ingestion of sulfonamides and some other drugs.

The normally small quantities of amino acids in the urine may be much increased in advanced liver
disease, in failure of tubular reabsorption, and in certain diseases due to inborn errors of protein
metabolism. Phenylketonuria, a disease identified by the presence of phenylpyruvic acid in the urine,
is due to lack of the enzyme phenylalanine hydroxylase, so that phenylalanine is converted not to
tyrosine but to phenylpyruvic acid. The presence of this acid in blood and tissues causes mental
retardation; it may be readily detected if the urine of every newborn infant is tested. Restriction of
phenylalanine in the diet in such cases may be beneficial. Alkaptonuria, a disease identified by the
presence of homogentisic acid in the urine, is due to lack of the enzyme that catalyzes the oxidation
of homogentisic acid; deposits of the acid in the tissues may cause chronic arthritis or spinal disease.
Other such disorders are cystinuria, the presence of the amino acid cystine in the urine, when the
bladder may contain cystine stones; and maple syrup disease, another disorder involving abnormal
levels of amino acid in the urine and blood plasma.

Lecture 3
Hormonal Control of Osmoregulatory Functions

Renin-Angiotensin-Aldosterone

3
The renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood
pressure and water (fluid) balance. This system proceeds through several steps to produce
angiotensin II, which acts to stabilize blood pressure and volume.

Renin is an aspartyl protease secreted by the juxtaglomerular apparatus, a cellular complex adjacent
to the renal glomeruli, lying between the afferent arteriole and the distal convoluted tubule. Renin is
derived from prorenin by proteolytic action, and secretion increases in response to a reduction in
renal artery blood flow, possibly mediated by changes in the mean pressure in the afferent arterioles,
and b-adrenergic stimulation. Renin splits a decapeptide (angiotensin I) from a circulating a2- globulin
known as renin substrate. Another proteolytic enzyme, angiotensin-converting enzyme (ACE), which
is located predominantly in the lungs but is also present in other tissues such as the kidneys, splits off
a further two amino acid residues. This is the enzyme that ACE inhibitors (used to treat hypertension
and congestive cardiac failure) act on. The remaining octapeptide, angiotensin II, has a number of
important actions:

 It acts directly on capillary walls, causing vasoconstriction, and so probably helps to maintain
blood pressure and alter the glomerular filtration rate (GFR). Vasoconstriction may raise the
blood pressure before the circulating volume can be restored.
 It stimulates the cells of the zona glomerulosa to synthesize and secrete aldosterone.

 It stimulates the thirst center and so promotes oral fluid intake.

 It stimulates the renal tubules to reabsorb more sodium

4
  Also triggers the release of anti-diuretic hormone (ADH) from the hypothalamus, leading to
water retention in the kidneys.

Poor renal blood flow is often associated with an inadequate systemic blood pressure. The release of
renin results in the production of angiotensin II, which tends to correct this by causing aldosterone
release, which stimulates sodium and water retention and hence restores the circulating volume.
Thus, aldosterone secretion responds, via renin, to a reduction in renal blood flow. Sodium excretion
is not directly related to total body sodium content or to plasma sodium concentration.

Role of Epinephrine and Norepinephrine in Kidney Function

Epinephrine and norepinephrine are released by the adrenal medulla and nervous system
respectively. They are the flight/fight hormones that are released when the body is under extreme
stress. During stress, much of the body’s energy is used to combat imminent danger. Kidney function
is halted temporarily by epinephrine and norepinephrine. These hormones function by acting directly
on the smooth muscles of blood vessels to constrict them. Once the afferent arterioles are
constricted, blood flow into the nephrons of the kidneys stops. These hormones go one step further
and trigger the renin-angiotensin-aldosterone system, the hormone system that regulates blood
pressure and water (fluid) imbalance.

Antidiurectic Hormone

Antidiuretic hormone or ADH (also called

vasopressin) helps the body conserve water when
body fluid volume, especially that of blood, is low.
Antidiuretic hormone is a polypeptide with a half-life
of about 20 min that is synthesized in the supraoptic
and paraventricular nuclei of the hypothalamus and,
after transport down the pituitary stalk, is secreted
from the posterior pituitary gland. ADH secretion is
stimulated in response to the low intravascular
pressure of severe hypovolaemia, The stress due
to, for example, nausea, vomiting and pain may also
increase ADH secretion. Inhibition of ADH secretion
occurs if the extracellular osmolality falls, for
whatever reason.

Antidiuretic hormone, by regulating aquaporin 2,

enhances water reabsorption in excess of solute
from the collecting ducts of the kidney and so dilutes

5
the extracellular osmolality. Aquaporins are cell membrane proteins acting as water channels that
regulate water flow. When ADH secretion is a response to a high extracellular osmolality with the
danger of cell dehydration, this is an appropriate response. However, if its secretion is in response to
a low circulating volume alone, it is inappropriate to the osmolality. The retained water is then
distributed throughout the TBW space, entering cells along the osmotic gradient; the correction of
extracellular depletion with water alone is thus relatively inefficient in correcting hypovolaemia.
Plasma osmolality normally varies by less than 1–2 per cent, despite great variation in water intake,
which is largely due to the action of ADH. ADH also acts as a vasoconstrictor (constricting blood
vessels) and increases blood pressure during hemorrhaging.

Mineralocorticoids

Mineralocorticoids are hormones synthesized by the adrenal cortex that affect osmotic balance. One
type of mineralocorticoid, known as aldosterone, regulates sodium levels in the blood. Almost all of
the sodium in the blood is reclaimed by the renal tubules under the influence of aldosterone. As
sodium is always reabsorbed by active transport and water follows sodium to maintain osmotic
balance, aldosterone manages not only sodium levels, but also the water levels in body fluids.
Aldosterone also stimulates potassium secretion concurrently with sodium reabsorption. By contrast,
absence of aldosterone means that no sodium is reabsorbed in the renal tubules; all of it is excreted
in the urine. In addition, the daily dietary potassium load is not secreted; retention of potassium ions
(K+) can cause a dangerous increase in plasma K+ concentration. Patients who have Addison’s
disease have a failing adrenal cortex and cannot produce aldosterone. They constantly lose sodium
in their urine; if the supply is not replenished, the consequences can be fatal.

Atrial Natriuretic Peptide Hormone

The atrial natriuretic peptide (ANP) hormone lowers blood pressure by acting as a vasodilator
(dilating or widening blood vessels). It is released by cells in the atrium of the heart in response to
high blood pressure and in patients with sleep apnea. ANP affects salt release; because water
passively follows salt to maintain osmotic balance, it also has a diuretic effect. ANP also prevents
sodium reabsorption by the renal tubules, decreasing water reabsorption (thus acting as a diuretic)
and lowering blood pressure. Its actions suppress the actions of aldosterone, ADH, and renin.

Urine components Normal

range
Color yellow
Transperancy transperant
specific gravity 1,010-1,025 g/L
Acidity 4-8 pH

Proteins <0,140 g/L

Glucose <0,8 Mmol/L
Keton bodies -
Bilirubin -
Uribilinogen -
6
Epithelial cells 0-10 Cells in eyeshot
leicocytes 0-6 Cells in eyeshot
Erythrocyte 0-3 Cells in eyeshot
Hyline casts 0-10 Cells in eyeshot
Granular casts -
Erythrocute casts -
Bacteries -
Salt cristals