Medical site

Gonadotropic hormones and their effect on ovaries

noreply@blogger.com (Anonymous) — Sat, 31 Aug 2013 14:22:00 +0000

The ovarian changes during the female sexual cycle depend completely on the hormones FSH and LH secreted by the anterior pituitary.

The ovaries that are not stimulated by these hormones remain inactive, that’s what occurs in childhood when no FSH and LH secreted. At ages of 9-10 years the anterior pituitary begin to secrete FSH and LH which results in female sexual cycle between age of 11-16 years. This period is called puberty and the first menstrual cycle is called menarche. During fetal life, the ovaries are stimulated by hCG from the placenta but after birth the stimulation is lost.

Both FSH and LH are glycoproteins, during each month the is a cyclical increase or decrease of both FSH and LH, FSH and LH stimulate their ovarian target cells by combination with highly specific FSH and LH receptors in the cell membrane, the activated receptors in turn increase the rate of secretion of these cells and their growth and their proliferation.

Androgen

noreply@blogger.com (Anonymous) — Thu, 29 Aug 2013 09:57:00 +0000

Androgenic steroid hormones are the male sex hormones, their function are:

1- Differentiation of the male reproductive tract and brain during fetal life.

2- Stimulation of the testis descend during the last three months of gestation.

3- Stimulation, maturation and maintenance of reproductive tract.

4- Maintenance of spermatogenesis in adult testis.

5- Negative feedback regulation of LH secretion by the pituitary.

Androgens also stimulate development of male secondary sex characters including:

1- Growth of facial, chest, axillary and pubic hair as well as hair recession and balding.

2- Hypertrophy of the laryngeal mucosa causing enlargement of the larynx and deepening of the voice.

3- Development of increased musculature due to increased protein deposition and nitrogen retention.

4- Enhancement of linear growth through stimulation of bone growth.

5- Androgens are very potent anabolic hormone that accelerate metabolism.

6- Increase thickness of skin over entire body and increase the rate sebaceous glands result in (acne).

7- Increase the total quantity of bone matrix and cause calcium retention, it causes narrowing of pelvic outlet and causes funnel like shape pelvis and increases strength of pelvis for load bearing.

8- Testosterone increases RBC count so adult male have 700000 RBCs more than in female.

9- Testosterone causes sodium reabsorption from kidney tubules.

Interstitial cells of leydig

noreply@blogger.com (Anonymous) — Thu, 29 Aug 2013 09:55:00 +0000

The principal function of leydig cells is to produce androgens. Leydig cells begin to secrete androgens during the 7th week of fetal life in response to hCG (human chorionic gonadotropin) which is

produced by the placenta. During childhood when gonadotropin secretion is low, the leydig cells regress. When plasma LH levels rise again at puberty, the leydig cells differentiate again and secrete steroids.

Inhibin + Androgen binding protein + Estrogen

noreply@blogger.com (Anonymous) — Thu, 29 Aug 2013 09:54:00 +0000

Inhibin

Is a protein that selectively inhibits the synthesis and secretion of FSH by the pituitary gonadotropes.

Androgen binding protein

Is protein that binds androgens. It is found both in the luminal fluid and plasma. ABP is concentrated in the luminal fluid and in the epididymis and its role is to carry testosterone within the sertoli cells and from the testis to the epididymis in order to maintain high testosterone concentration.

Estrogen

The principle estrogens in the plasma of adult males are estradiol and estrone, only 10%-20% of the circulatory estrogens are synthesized by sertoli cells in the testis, the remainder originate through the extra gonadal conversion of testosterone and androstenedione.

Sertoli cells

noreply@blogger.com (Anonymous) — Thu, 29 Aug 2013 09:53:00 +0000

Sertoli cells have many functions:

1- Provision of nutrients to germ cells.

2- Synthesis of multiple proteins that are secreted into the luminal fluid including caeruloplasm

in, acidic glycoprotein and transferrin.

3- Synthesis of estrogen.

4- Production of androgens binding protein (ABP).

5- Phagocytosis of damaged germ cells.

6- Synthesis and secretion of inhibin.

testes

noreply@blogger.com (Anonymous) — Thu, 29 Aug 2013 09:52:00 +0000

The testes serve three main functions:

1- Production of gametes.

2- Secretion of hormones that cause differentiation of the brain and reproductive tract during fetal and neonatal development, maintain the structure and function of the reproductive tract, it promotes the development of sexual characteristics.

3- Feedback regulation of the hypothalamus –pituitary hormones secretion.

The seminiferous tubules are lined with sertoli cells and the spermatogonia. The sertoli cells are linked by tight junctional complexes to form the sertoli cells barrier which limits the movement of fluid and nutrients between interstitial space of the testis and the lumen of seminiferous tubules, lipid soluble substances such as steroids (androgen) are able to traverse the barrier and enter the lumen of the seminiferous tubules, the barrier prevent the penetration of immunoglobulin that might interfere with the development of spermatozoa.

Anatomy of male reproductive system

noreply@blogger.com (Anonymous) — Thu, 29 Aug 2013 09:50:00 +0000

The testis composed of 900 coiled seminiferous tubules, each

average more than 5 meters length in which the sperms are

found. Between the seminiferous tubules are the interstitial

cells of leydig for synthesis of testosterone. The sperms pass

from the

seminiferous tubules to the epididymis which is coiled and

about 6 meters length, this leads to the vas deferens which

enlarges into the ampulla before entering into the prostate

gland. The seminal vesicles are two, one located on each side of

the ampulla, empties into the prostatic end of the ampulla and

the contents from the ampulla and seminal vesicles pass into

the ejaculatory duct leading to urethra.

Prevention of Blood Clotting in the Normal Vascular system

noreply@blogger.com (Anonymous) — Tue, 27 Aug 2013 08:31:00 +0000

I: Endothelial surface Factors:

1:The smoothness of the endothelial cell surface : prevent contact activation of the intrinsic clotting

2:Layer of glycocalyx on the endothelium it is muco- polysaccharide adsorbed to the surfaces of the

endothelial cells repels clotting factors & platelets.

3:Thrombomodulin remove thrombin.How? thrombin-thrombomodulin complex activate

protien-C which act as anti-coagulant, inactivate Va, VIIIa & increases the activity of tissue

plasminogen activator (t-PA).

II --Anti– clotting mechanism

The tendency of blood to clot is balanced in vivo by limiting reactions that tend to prevent clotting inside the blood vessels and to break down any clots that do form when a vascular injury occurs.

The activated coagulation (clotting) factors must remain contained in a localized area.

1.Coagulation automatically initiates fibrinolysis.

2. Circulating blood contain biochemical inhibitors (anticoagulants) that prevent coagulation & formation of fibrin.

III-Process of fibrinolysis :

Blood contains proteolytic enzymes known as the “fibrinolytic system” dissolve fibrin .The major protein of the fibrinolytic system is plasminogen (inactive) .

When a clot is formed, the injured tissues and vascular endothelium, very slowly release a powerful activator called Tissue plasminogen activator (T-PA) that converts plasminogen into its active formplasmin → F&fibrinogen→FDP

The fibrinolytic & coagulation systems are interrelated under normal conditions . . In rare conditions if the fibrinolytic system is activated without the activation of the coagulation system. This may result in severe bleeding problems .

If clotting mechanism is activated without activation of fibrinolytic system this may result in clotting disorders (thrombosis).

IV- Anticoagulants:

Substances that prevent coagulation mechanism i.e. prevent coagulation factors from initiating clot formation. Types:

1- Intravascular anticoagulants Prevention of clotting in(NVS):-

a. Antithrombin III: is a plasma protein produced by the liver & inactivates thrombin.85-90% of thrombin adsorb to fibrin fibers this prevent spread of thrombin,the remaining thrombin combine with antithrombin III which block & inactivate thrombin action.

b. Heparin: produced by basophils & mast cells. Increases the effectiveness of antithrombin III about1oo to1000 folds for removing thrombin. Their combination remove activated factors XII,XI,X&IX It is widely used in medical practice to prevent intravascular clotting.

c. Prostacylin : is a prostaglandin derivative produced by endothelial cells. is a vasodilator & inhibit the release of clotting factor from platelets inhibits their aggregation.

d. Plasma Ca++ in vivo, a low plasma Ca++ level is enough it does not interfere with blood clotting.

2- Anticoagulants used outside the body:

a-Heparin

b-EDTA (ethylenediamine Tetra acetic acid prevents clot formation by binding to calcium making inaccessible for clotting reactions.

c-Citrate e.g. sodium citrate have the same

action of EDTA .Citrate is not toxic to the body.

d-Oxalate ion: which precipitate Ca ions, Oxalate

combine with calcium and form insoluble salt. Oxalate

is toxic to the body.

e-Blood bank anticoagulants. Examples: a. acid-citrate dextrose. b. citrate – phosphate dextrose

3- Anticoagulant for clinical use

a. Heparin b. Cumarins such as warfarin

Heparins and cumarins are anticoagulants used

for the treatment of venous thrombosis (i.e.

formation of clots inside blood vessels).warfarin has depressant effect on liver formation of II,VII,IX&XII

(Pathophysiology of haemostasis)

Defect in the haemostatic mechanism:

1.Bleeding disorder: lead to prolonged bleeding.

2.Clotting disorder lead to increase clotting time

. clotting disorders: result from deficiency of any one or more of the clotting factors . For example Hemophilias.

Hemophilia A: caused by deficiency of antihaemophilic factor A (i.e. factor VIIIc). about 85% of all cases are hemophilia A.it is X-linked ,♂ have the disease &♀ are carriers .

This type of hemophilia is also called classic hemophilia It is hereditary sex - linked recessive disorder has a prevalence of 1 in 10000 persons . Those patients have

severe hemorrhagic complications in response to truma

Treatment: includes replacement therapy with factor VIII.

Hemophilia B:Occurs as a result of a deficiency of

factor IX. It is also known as “Christmas disease” and accounts for approximately 12% of all hemophilia's.

Hemophilia C: The least common of three major types of hemophilias, caused by deficiency of factor XI & accounts less than 3% of all hemophilia. It is inherited disease. Hemophilia C is also known as "Rosenthal syndrome.“

In all types of hemophilia bleeding usually does not occur except after trauma. Bleeding can last for weeks after extraction of a tooth. Bleeding may occur into the muscles & may result into hematomas. Bleeding in hemophilia is usually from larger vessels.

In all types of hemophilias and Vit K deficiency OR if there is abnormality and/or deficiency of any of the clotting factors the CLOTTING TIME is PROLONGED.

While the BLEEDING TIME is NORMAL

Clotting Disorders:

Inappropriate clotting mechanisms in intact blood vessels results in fibrin clot formation, a phenomenon known as intravascular thrombosis. Thrombosis may be due to activation of clotting factors or due to lack of inhibitory factors (anticoagulants) to neutralize activated clotting factors. Once a thrombus (clot) has developed, it break away from its attachment to flow along with the blood such freely flowing clots are known as emboli.

3- Vitamin K deficiency: This is required for synthesis of clotting factors II ,VII,IX & X.

Laboratory diagnosis of bleeding disorders:

1. Bleeding time test.

2. Capillary fragility test.

3. Platelet count.

4. platelets functions Test.

Coagulation Screening Tests:

1. Clotting Time.

2.Thrombin Time (TT) .

3.Prothrombin Time (PT).

4.Partial Thromboplastin Time. (PTT).

5.Secreening of each of the clotting factors alone.

Coagulation tests

n Thrombin Time(TT): Exogenous thrombin is added,intrinsic& extrinsic pathways are bypassed so if fibrinogen is deficient TT is prolonged Normal value is 18-20 seconds.

n Prothrombin Time (PT):Assesses the Extrinsic pathway factors because factor III is added,the intrinsic factors are bypassed.Normally PT equals 10-15 sec.

n Partial Thromboplastin Time (PTT): Measures the competency of the intrinsic pathway Normally =35 to 45 seconds.

Rh-Blood TYPES

noreply@blogger.com (Anonymous) — Tue, 27 Aug 2013 08:24:00 +0000

Rh-Blood groups:

The Rh-factor named for the rhesus monkey because it was first studied using the blood of this animal.

Rh-agglutinogens (antigens): there are six common types of Rh-antigens each of which is called Rh-factor. These types are C, D, E, c, d, & e.The type D (Rh)-antigen is more antigenic.

The major difference between ABO system and Rh system is that agglutinins causing transfusion reactions in ABO developed spontaneously, where in the Rh system spontaneous agglutinins NEVER occur,unless the Rh^- person exposed first to Rh+ blood by transfusion.,Or if the ^Rh-femaleshaving ^(Rh+)child, anti-D antibodies developed in her blood slowly reaching maximum concentration about 2-4 months later.Exposure to another Rh+ blood, transfusion reaction occurs . anyone who has antigen D on RBC membrane is said to be Rh-positive (Rh+) or D-positive (D+) about 85% of population are Rh+, while persons who does not have antigen D on their RBC is said to be Rh-negative (Rh-) or D- & about 15% are D^- (Rh^- Rh+ is dominant while Rh- is recessive.

Rh agglutinins: The Rh+ individual has no antibody in their plasma. The Rh- person has also no antibody D in the plasma, but Rh- individual forms the antibody D when transfused with D⁺ (Rh⁺) cells. Antibodies against Rh-antigen do not develop unless an Rh- person is exposed to Rh+ blood. This can occur through a transfusion or entrance of fetal blood into the maternal circulation across the placenta.

Table: Rh –type, agglutiongen, agglutinin, and % of each Rh -group

Rh-type	Agglutinogen on RBC	Agglutinins in plasma	%
Rh⁺	D	-	85
Rh^-	No D antigen	- Unless exposed to Rh+ blood	15

The ABO blood type & the Rh blood type usually are designated together.

(ABO system)^{(Rh system)}

For example a person designated as A positive (A+) is blood group A in the ABO- system and Rh+ in the Rh blood group. This person has antigens A & D on RBC & antibody-B & no antibody-D in the plasma.

Rh –Transfusion Reaction:

is the reaction between (antigen D )in Rh+ blood of donor & antibody D in Rh- blood of recipient.

When an Rh- receives a first transfusion of Rh+ blood, the recipient becomes sensitized to the Rh+ antigen & produces antibodies D.

If the same person receive a second transfusion of Rh+ blood, transfusion reaction results & clumping (agglutination) of RBC’s occurs.

Hemolytic disease of newborn (HDN) or Erythroblastosis Fetalis:

HDN: is a disease of the fetus & neonate. characterized by agglutination of RBCs of the fetus due to reaction between antigen D in the fetus RBC & antibody-D produce by the mother. Fetus may develop hemolytic anemia in two major ways as a consequence of developing antibodies.

1. Rh- incompatibility. 2. ABO- incompatibility.

HDN due to Rh-incompatibility.

Mother Rh- (Rh- Rh - ) X father+ (Rh+ Rh-)

Fetus 50% Rh+ (Rh+ Rh^-)

& 50% Rh^-(Rh^-Rh^-)

A 100% chance of producing an Rh+ fetus if the father is homozygous (Rh+ Rh+).

Mother (Rh- Rh-) X father (Rh+ Rh+)

Fetus 100% Rh+ Rh^-

At the time of delivery small amount of fetal blood which contain antigen D leak into the maternal circulation & some of them develop antibody D during postpartum period.

In the woman’s first pregnancy there is no problem. The leakage of fetal blood which contain antigen D is usually the result of a tear in the placenta that takes place during delivery. Thus there is no enough time for the mother to produce enough D- antibodies.

In the later pregnancies, a problem can arise because the mother has been sensitized (i.e. formed antibody-D) against antigen D.

When the mother becomes pregnant again with another Rh+ fetus she had produced large amounts of Rh-antibodies & HDN develops in the fetus. The term erythroblastosis fetalis is also used to describe HDN since blood smears from these babies show the presence of many immature red blood cells (erythroblasts).

Prevalence of disease:

About 3% of second Rh –positive babies exhibit some signs of HDN;

17% of the third babies exhibit the disease; and the incidence rises progressively with subsequent pregnancies.

About 50% of Rh negative individuals are sensitized (develop anti-Rh titer) by transfusion of Rh⁺blood.

Symptoms of disease:

1.Hemolysis,&severe jaundice

2. edema (hydrops fetalis).

3.Kernicterus due to deposition of bilirubin in the basal ganglia which result in brain damage & mental retardation.

4. Splenomegaly & hepatomegaly (i.e. enlargement of spleen & liver).

Laboratory findings of HDN:

Presence of erythroblasts and reticulocytosis in the blood smear.

Low PCV. & low hemoglobin concentration .

Level of unconjugated bilirubin will be high (more than 10 mg/dl).

Treatment of HDN

1.Treatment of mother:

The Rh- woman should be given an injection of single dose of anti-D antibodies within 72 hours during the postpartum period or during pregnancy or immediately after each abortion. The injection contains anti-D against antigen-D.The injected antibodies will bind to Rh – antigens of fetus erythrocytes that may have entered the mother's blood and destroy the antigen D on fetal RBC before the immune system of the mother is activated. In other words, the fetal RBCs will be destroyed before the mother is able to develop her own antibodies against these erythrocytes. Hence she will be able to conceive another Rh+ child without any complication.

HDN due to ABO-incompatibility: when a mother of type O blood becomes pregnant & the fetus has type A or B antigens on RBC this may result in anemia known as HDN.

The ABO-HDN is more common than Rh-HDN. Approximately 23% of all pregnancies involve incompatible ABO system.

1- Blood Typing : blood typing and blood matching is done by mixing the blood with saline. Then it is mixed with anti-A,anti-B & anti-D after several minutes ,look for agglutination .
2- Cross Matching : RBCs of the donor mixed with the serum of the recipient and look for agglutination.If it is +ve the blood is incompatible,if there is no agglutination the blood of the donor and recipient is compatible.

Acute kidney Shutdown

There are three causes:

1-Toxic substances from hemolyzing blood due to antigen-antibody reaction cause renal vasoconstriction.

2- circulatory shock due to loss of RBCs,the blood pressure decreases renal blood flow and urine out put decreases.

3-Excess hemoglobin of haptoglobin leak into kidney tubule and precipitate into tubule and block them.

ALL OF THE ABOVE 3 CAUSES ACUTE RENAL SHUT DOWN AND DEATH WITHIN AWEEK.

Effect of temperature on spermatogenesis

noreply@blogger.com (Anonymous) — Mon, 26 Aug 2013 08:17:00 +0000

Normal temperature to spermatogenesis is 32o C, increasing temperature as hot bath of 48oC for 30 minutes reduces sperm count to 90%, sperms ca

n live in male genital tract for weeks at low temperature and can be preserved for years at -100 C (Bank for AID).

Neuroendocrine Regulation of the Testis

noreply@blogger.com (Anonymous) — Sun, 25 Aug 2013 10:21:00 +0000

Neuroendocrine Regulation of the Testis:-

In hypothalamus GnRH secreted in pulses one pulse every 3 hours, if secreted continuously the anterior pituitary not responds to it, anterior pituitary secrete

FSH AND LH (LH follows the pulsatile pattern of GnRH secretion while FSH increase or decrease according to demand.

FSH has specific receptors on steroli cells, after binding to it:

1. They stimulate spermatogenesis.

2. Stimulate sertoli cells secretion estrogen and inhibin which have –ve feedback on anterior pituitary LH effect on leydig cells stimulate it to secrete testosterone which acts locally on sertoli cells that effect spermatogenesis and estrogen secretions also effect target tissues outside the testis (sexual characteristics ).

Testosterone have negative feedback on anterior pituitary that inhibit FSH and LH secretion which causes negative feedback on hypothalamus to decrease GnRH secretions

The mature sperm is capable of movement in a straight line. Its activity is increased with increasing temperature, also increase neutral & alkaline medium & decreased in acidic medium. Average PH of semen is 7.5, the sperm remain in genital tract for 1-2 days.

Function of seminal vesicle

noreply@blogger.com (Anonymous) — Sun, 25 Aug 2013 09:57:00 +0000

Function of seminal vesicle:-

The secretion of seminal vesicle form 60% of total volume,its mucoid contain fructose,citric acid and other nutrients,also prostaglandin and fibrenogin

, prostaglandin are belived to aid fertilization by :

1. Reacting with cervical mucous making it more receptive to sperm movement

2. Causing reverse peristatitic,contraction of uterus and fallobian tubes to move the sperm toward ovaries

Semen

noreply@blogger.com (Anonymous) — Sun, 25 Aug 2013 09:56:00 +0000

Semen:

The fluid that ejaculated at the time of orgasm contains sperms and secretion of seminal vesicle, prostate and cowpers gland.

Normal semen volume 2.5-5 ml,

sperm count 20,000,000 per ml, activity (motility) 50 %, progressive movement 60% .

Subfertile means decrease in volume count …. Etc..

Capacitation of spermatozoa:-

Several changes believe to occur that activate the sperm for final process of fertilization, these changes are:-

1. The uterine and fallobian tube fluids washaway the inhibitory factors that suppress sperm motility

2. The sperm deposited in female genital tract loses much cholesterol from the head, so the membrane at the head of the sperm becomes weak.

3. The membrane of sperm’s head become small permeable for Ca, and Ca enter the sperm giving it powerful motion , without capacitation the sperm cannot fertilize the ovum

Function of prostate gland

noreply@blogger.com (Anonymous) — Sat, 24 Aug 2013 10:27:00 +0000

The prostate gland secrete a thin milky fluid (30% of total vol.) contain citrate ions, calcium ions, phosphate ions and clotting

enzyme and fibrinolysin, prostatic fluid is alkaline and helps to neutralized the acidity of vaginal secretion and of the vas deferens.

[Sperm don’t live in acidic medium (if it lived-according to the PH-) it will be not capable to fertilize the ovum]

Maturation of sperm in epididymis

noreply@blogger.com (Anonymous) — Sat, 24 Aug 2013 10:26:00 +0000

The sperm after its formation in the seminiferous tubules pass into the epididymis, they remain for 18-24 hours and become capable of motility, although in the epididymal fluid there are inhibitory

proteins which prevent sperm motility until ejaculation, after ejaculation the sperm become motile and capable of fertilization of the ovum, this process called maturation, from sertoli and epididymis there is a fluid ejaculated with the sperms contains estrogen and testosterone, this is essential for maturation, the adult testis form about 120 million sperms per day sperms, small quantity of them stored in the epididymis, while large quantities stored in vas deferens.

Formation of sperms

noreply@blogger.com (Anonymous) — Sat, 24 Aug 2013 10:19:00 +0000

Formation of sperms:-

The sperms is composed of head and tail , the head composed of condensed nucleus with only a thin cytoplasmic cell membrane layer around its surface.

On the outside of anterior two third of the head is a thick cap called acrosome, This contain a number of enzymes including Hyaluronidase which has a powerful proteolitic enzymes ,these enzymes play important role it allowing the sperm to fertilize the ovum.

The tail of the sperm called flagellum which responsible of movement. The tail provides motility for the sperm, normal sperm moves in a velocity of 1-4 mm/min.

Hormonal factors that stimulate spermatogenesis

noreply@blogger.com (Anonymous) — Sat, 24 Aug 2013 10:18:00 +0000

Hormonal factors that stimulate spermatogenesis :

1. LH secreted by anterior pituitary stimulates leydig cells to secrete testosterone.

2. Testosterone secreted by leydig cells is essential for growth and division of germinal cells in forming sperms.

3. FSH also secreted by anterior pituitary stimulates secretion of sertoli cells and without this stimulation spermatogenesis will not occur, in addition it promotes production of ABP.

4. Estrogen formed by sertoli cells essential for spermatogenesis, ABP is important for sperm maturation (capability of movement).

5. GH promotes early division of spermatogonia and its absence results in deficient or absence spermatogenesis (in dwarf).

6. Prolactin it may potentiate the stimulatory effect of LH on lydig cells and of testosterone on many of its target cells (in hyperprolactinemia causes infertility).

Acrosome reaction

noreply@blogger.com (Anonymous) — Sat, 24 Aug 2013 10:17:00 +0000

Acrosome reaction

The acrosome enzyme hyaluronidase and proteolytic enzymes released to open a pathway

for passage of sperm head through zona pellucida within 30 minutes, so fertilization will occur.

Why does only one sperm enter the oocyte?

1- Only few sperms get as far as the zona pellucida so that it might be 10, 20 or 30 minutes before the 2nd sperm arrives.

2- Within few minutes after the 1st sperm penetrate the zona pellucida, Ca++ diffuse through the oocyte membrane and cause release of cortical granules that prevent binding of additional sperms.

3- The oocyte membrane its fusion with sperm is believed to be electrically depolarized.

Spermatogenesis (sperms formation)

noreply@blogger.com (Anonymous) — Sat, 24 Aug 2013 10:16:00 +0000

The seminiferous tubules contain large number of germ cells called spermatogonia, located in 2-3 layers. In the 1st stage of spermatogenesis, type A spermatogonia divided 4 times (mitosis) to form 16 more

differentiated cells called type B spermatogonia, at this stage spermatogonia migrate centrally among sertoli cells.

For a period of 24 days, each spermatogonium that crosses the barrier into sertoli cell layer becomes by mitosis a large primary spermatocyte. At the end of 24 days, each primary spermatocyte divide to form 2 secondary spermatocytes, this division is called the 1st meiotic division, in this process each of the 46 chromosomes become 2 chromatids, so each secondary spermatocyte have 23 chrom.

Within 2-3 days a 2nd meiotic division occurs in which the 2 chromatids in each of the 23 chrom split apart forming 2 sets of 23 chrom, one set passing into one daughter spermatid.

The importance of these meiotic divisions is that the eventual sperms that fertilized the ovum provide one half of the genetic material to the fertilized ovum and the ovum will provide the other half.

These stages from spermatogonia to spermatid are androgen dependent.

During the next few weeks after meiosis each spermatid is nursed and reshaped by its sertoli cells and changed into a sperm by losing some of its cytoplasm, formation of compact head and formation of a tail, maturation of spermatid to spermatozoa depends on estrogen (does not depend on testosterone) acting on sertoli cells. The entire period of spermatogenesis takes 74 days.

Transport of Substances Through the Cell Membrane “Diffusion” Versus “Active Transport.”

noreply@blogger.com (Anonymous) — Thu, 22 Aug 2013 09:22:00 +0000

Transport of Substances Through the Cell Membrane “Diffusion” Versus “Active Transport.”

Transport through the cell membrane, either directly through the lipid bilayer or through the proteins, occurs by one of two basic processes:

(1) Diffusion.

(2) Active transport.

Diffusion: means random molecular movement of substances molecule by molecule, either through intermolecular spaces in the membrane or in combination with a carrier protein.

Active transport: means movement of ions or other substances across the membrane in combination with a carrier protein in such a

way that the carrier protein causes the substance to move against an energy gradient, such as from a low-concentration state to a high-concentration state. This movement requires an additional source of energy besides kinetic energy.

Diffusion Through the Cell Membrane

Simple diffusion and facilitated diffusion.

Simple diffusion: Means that kinetic movement of molecules or ions occurs through a membrane opening or through intermolecular spaces without any interaction with carrier proteins in the membrane. The rate of diffusion is determined by the amount of substance available, the velocity of kinetic motion, and the number and sizes of openings in the membrane through which the molecules or ions can move. Simple diffusion can occur through the cell membrane by two pathways:

(1) Through the interstices of the lipid bilayer if the diffusing substance is lipid soluble.

(2) Through watery channels that penetrate all the way through some of the large transport proteins.

Facilitated diffusion:

Requires interaction of a carrier protein. The carrier protein aids passage of the molecules or ions through the membrane by binding chemically with them and shuttling them through the membrane in this form.

Diffusion of Lipid-Soluble Substances Through the Lipid Bilayer.

One of the most important factors that determines how rapidly a substance diffuses through the lipid bilayer is the lipid solubility of the substance. For instance, the lipid solubilities of oxygen, nitrogen, carbon dioxide, and alcohols are high, so that all these can dissolve directly in the lipid bilayer and diffuse through the cell membrane in the same manner that diffusion of water solutes occurs in a watery solution.

Diffusion of Water and Other Lipid-Insoluble Molecules Through Protein Channels.

Even though water is highly insoluble in the membrane lipids, it readily passes through channels in protein molecules that penetrate all the way through the membrane. Other lipid-insoluble molecules can pass through the protein pore channels in the same way as water molecules if they are water soluble and small enough.

Diffusion Through Protein Channels, and “Gating” of These Channels:

Substances can move by simple diffusion directly along these channels from one side of the membrane to the other. The protein channels are distinguished by two important characteristics:

(1) They are often selectively permeable to certain substances.

(2) Many of the channels can be opened or closed by gates.

Selective Permeability of Protein Channels.

Many of the protein channels are highly selective for transport of one or more specific ions or molecules. This results from the characteristics of the channel itself, such as its diameter, its shape, and the nature of the electrical charges and chemical bonds along its inside surfaces. To give an example, one of the most important of the protein channels:

Sodium channels: They are only 0.3 by 0.5 nanometer in diameter, the inner surfaces of this channel are strongly negatively charged. These strong negative charges can pull small dehydrated sodium ions into these channels, actually pulling the sodium ions away from their hydrating water molecules. Thus, the sodium channel is specifically selective for passage of sodium ions.

Potassium channels: These channels are slightly smaller than the sodium channels, only 0.3 by 0.3 nanometer, but they are not negatively charged, and their chemical bonds are different. Therefore, no strong attractive force is pulling ions into the channels, and the potassium ions are not pulled away from the water molecules that hydrate them.

The hydrated form of the potassium ion is considerably smaller than the hydrated form of sodium because the sodium ion attracts far more water molecules than does potassium. Therefore, the smaller hydrated potassium ions can pass easily through this small channel, whereas the larger hydrated sodium ions are rejected, thus providing selective permeability for a specific ion.

Gating of Protein Channels.

Gating of protein channels provides a means of controlling ion permeability of the channels. It is believed that some of the gates are actual gate like extensions of the transport protein molecule, which can close the opening of the channel or can be lifted away from the opening by a conformational change in the shape of the protein molecule itself. The opening and closing of gates are controlled in two principal ways:

1. Voltage gating.

when there is a strong negative charge on the inside of the cell membrane, this presumably could cause the outside sodium gates to remain tightly closed; conversely, when the inside of the membrane loses its negative charge, these gates would open suddenly and allow tremendous quantities of sodium to pass inward through the sodium pores. This is the basic mechanism for eliciting action potentials in nerves that are responsible for nerve signals. While the potassium gates are on the intracellular ends of the potassium channels, and they open when the inside of the cell membrane becomes positively charged. The opening of these gates is partly responsible for terminating the action potential.

2. Chemical (ligand) gating.

Some protein channel gates are opened by the binding of a chemical substance (a ligand) with the protein; this causes a conformational or chemical bonding change in the protein molecule that opens or closes the gate. This is called chemical gating or ligand gating. One of the most important instances of chemical gating is the effect of acetylcholine on the so-called acetylcholine channel. Among the most important substances that cross cell membranes by facilitated diffusion are glucose and most of the amino acids. In the case of glucose, the carrier molecule has been discovered, and it has a molecular weight of about 45,000; it can also transport several other monosaccharides that have structures similar to that of glucose, including galactose. Also, insulin can increase the rate of facilitated diffusion of glucose as much as 10-fold to 20-fold. This is the principal mechanism by which insulin controls glucose use in the body.

Factors That Affect Net Rate of Diffusion:

(1) Concentration Difference : The rate at which the substance diffuses inward is proportional to the concentration of molecules on the

outside, because this concentration determines how many molecules strike the outside of the membrane each second.Conversely, the rate at which molecules diffuse outward is proportional to their concentration inside the membrane. Therefore, the rate of net diffusion into the cell is proportional to the concentration on the outside minus the concentration on the inside, or: Net diffusion μ (Co - Ci) in which Co is concentration outside and Ci is concentration inside.

(2) Membrane Electrical Potential. If an electrical potential is applied across the membrane, the electrical charges of the ions cause them to move through the membrane even though no concentration difference exists to cause movement.

(3) Effect of a Pressure Difference Across the Membrane. Considerable pressure difference develops between the two sides of a diffusible membrane. This occurs, for instance, at the blood capillary membrane in all tissues of the body. The pressure is about 20 mm Hg greater inside the capillary than outside.

“Active Transport” of Substances Through Membranes: At times, a large concentration of a substance is required in the intracellular fluid even though the extracellular fluid contains only a small concentration. This is true, for instance, for potassium ions.

Conversely, it is important to keep the concentrations of other ions very low inside the cell even though their concentrations in the extracellular fluid are great. This is especially true for sodium ions. Different substances that are actively transported through at least some cell membranes include sodium ions, potassium ions, calcium ions, iron ions, hydrogen ions, chloride ions, iodide ions, urate ions, several different sugars, and most of the amino acids.

Primary Active Transport Sodium-Potassium Pump

Sodium-potassium (Na+-K+) pump, a transport process that pumps

sodium ions outward through the cell membrane of all cells and at the same time pumps potassium ions from the outside to the inside. This pump is responsible for maintaining the sodium and potassium concentration differences across the cell membrane, as well as for

establishing a negative electrical voltage inside the cells.

The carrier protein is a complex of two separate globular proteins: a larger one called the (a) subunit, with a molecular weight of about 100,000, and a smaller one called the( b) subunit, with a molecular weight of about 55,000. Although the function of the smaller protein is not known (except that it might anchor the protein complex in the lipid membrane), the larger protein has three specific features that are important for the functioning of the pump:

1. It has three receptor sites for binding sodium ions on the portion of the protein that protrudes to the inside of the cell.

2. It has two receptor sites for potassium ions on the outside.

3. The inside portion of this protein near the sodium binding sites has ATPase activity.

To put the pump into perspective: When two potassium ions bind on the outside of the carrier protein and three sodium ions bind on the inside, the ATPase function of the protein becomes activated. This then cleaves

one molecule of ATP, splitting it to adenosine diphosphate (ADP) and liberating a high-energy phosphate bond of energy. This liberated energy is then believed to cause a chemical and conformational change in the protein carrier molecule, extruding the three sodium ions to the outside and the two potassium ions to the inside. As with other enzymes, the Na+-K+ ATPase pump can run in reverse.

Importance of the Na+-K+ Pump for Controlling Cell Volume.

One of the most important functions of the Na+-K+ pump is to control the volume of each cell. Without function of this pump, most cells of the body would swell until they burst. The mechanism for controlling the volume is as follows:

Inside the cell are large numbers of proteins and other organic molecules that cannot escape from the cell. Most of these are negatively charged and therefore attract large numbers of potassium, sodium, and other positive ions as well. All these molecules and ions then cause osmosis of water to the interior of the cell. Unless this is checked, the cell will swell indefinitely until it bursts. The normal mechanism for preventing this is the Na+-K+ pump. Note again that this device pumps three Na+ ions to the outside of the cell for every two K+ ions pumped to the interior.

Electrogenic Nature of the Na+-K+ Pump.

The fact that the Na+-K+ pump moves three Na+ ions to the exterior for

every two K+ ions to the interior means that a net of one positive charge is moved from the interior of the cell to the exterior for each cycle of the pump.This creates positivity outside the cell but leaves a deficit of positive ions inside the cell; that is, it causes negativity on the inside. Primary Active Transport of Calcium Ions

Calcium ions are normally maintained at extremely low concentration in the intracellular cytosol of virtually all cells in the body, at a concentration about 10,000 times less than that in the extracellular fluid. This is achieved mainly by two primary active transport calcium pumps. One is in the cell membrane and pumps calcium to the outside of the cell. The other pumps calcium ions into one or more of the intracellular vesicular organelles of the cell, such as the sarcoplasmic reticulum of muscle cells and the mitochondria in all cells. In each of these instances, the carrier protein penetrates the membrane and functions as an enzyme ATPase, having the same capability to cleave ATP as the ATPase of the sodium carrier protein. The difference is that this protein has a highly specific binding site for calcium instead of for sodium.

Primary Active Transport of Hydrogen Ions At two places in the body, primary active transport of hydrogen ions is very important: in the gastric glands of the stomach and in the late distal tubules and cortical collecting ducts of the kidneys.

Secondary Active Transport— Co-Transport and Counter Transport

When sodium ions are transported out of cells by primary active transport, a large concentration gradient of sodium ions across the cell membrane usually develops—high concentration outside the cell and

very low concentration inside. This gradient represents a storehouse of energy because the excess sodium outside the cell membrane is always attempting to diffuse to the interior. Under appropriate conditions, this diffusion energy of sodium can pull other substances along with the sodium through the cell membrane. This phenomenon is called co-transport; it is one form of secondary active transport. For sodium to pull another substance along with it, a coupling mechanism is required. This is achieved by means of still another carrier protein in the cell membrane.

The carrier in this instance serves as an attachment point for both the sodium ion and the substance to be co-transported. Once they both are attached, the energy gradient of the sodium ion causes both the sodium ion and the other substance to be transported together to the interior of the cell.

In counter-transport, sodium ions again attempt to diffuse to the interior of the cell because of their large concentration gradient. However, this time, the substance to be transported is on the inside of the cell and must be transported to the outside. Therefore, the sodium ion binds to the carrier protein where it projects to the exterior surface of the membrane, while the substance to be counter-transported binds to the interior projection of the carrier protein. Once both have bound, a conformational change occurs, and energy released by the sodium ion moving to the interior causes the other substance to move to the exterior.

Co-Transport of Glucose and Amino Acids Along with Sodium Ions Glucose and many amino acids are transported into most cells against large concentration gradients; the mechanism of this is entirely by co-

Fig. Postulated mechanism for sodium co-transport of glucose

transport, the transport carrier protein has two binding sites on its exterior side, one for sodium and one for glucose. Also, the concentration of sodium ions is very high on the outside and very low inside, which provides energy for the transport. A special property of the transport protein is that a conformational change to allow sodium movement to the

interior will not occur until a glucose molecule also attaches. When they both become attached, the conformational change takes place, and the sodium and glucose are transported to the inside of the cell at the same time. Hence, this is a sodium-glucose co-transport mechanism.

Sodium co-transport of the amino acids occurs in the same manner as for glucose, except that it uses a different set of transport proteins.

Other important co-transport mechanisms include co-transport of chloride ions, iodine ions, iron ions, and urate ions.

Sodium Counter-Transport of Calcium and Hydrogen Ions

Sodium-calcium counter-transport occurs through all or almost all cell membranes, with sodium ions moving to the interior and calcium ions to the exterior.

Sodium-hydrogen counter-transport occurs in the proximal tubules of the kidneys.

Active Transport Through Cellular Sheets: At many places in the body, substances must be transported all the way through a cellular sheet instead of simply through the cell membrane. Transport of this type occurs through the:

Intestinal epithelium.

Epithelium of the renal tubules.

Epithelium of the gallbladder.

Membrane of the choroid plexus of the brain and other membranes.

The basic mechanism for transport of a substance through a cellular sheet is:

(1) Active transport through the cell membrane on one side of the transporting cells in the sheet.

(2) Simple diffusion or facilitated diffusion through the membrane on the opposite side of the cell.

The epithelial cells are connected together tightly at the luminal pole by means of junctions called “kisses.” The brush border on the luminal surfaces of the cells is permeable to both sodium ions and water. Therefore, sodium and water diffuse readily from the lumen into the interior of the cell. Then, at the basal and lateral membranes of the cells, sodium ions are actively transported into the extracellular fluid of the surrounding connective tissue and blood vessels. This creates a high sodium ion concentration gradient across these membranes, which in turn causes osmosis of water as well. Thus, active transport of sodium ions at the basolateral sides of the epithelial cells results in transport not only of sodium ions but also of water. These are the mechanisms by which almost all the nutrients, ions, and other substances are absorbed into the blood from the intestine; they are also the way by which the same substances are reabsorbed from the glomerular filtrate by the renal tubules.

Fig: Basic mechanism of active transport across a layer of cells.

NUCLEUS & Nucleoli and Formation of Ribosomes

noreply@blogger.com (Anonymous) — Thu, 22 Aug 2013 09:20:00 +0000

Nucleus

: The nucleus is the control center of the cell. Briefly, the nucleus contains large quantities of DNA, which are the genes. The genes determine the characteristics of the cell’s proteins, including the structural

Proteins and the intracellular enzymes that control cytoplasmic and nuclear activities. The genes also control and promote reproduction of the cell itself. The genes first reproduce to give two identical sets of genes; then the cell splits by a special process called mitosis to form two daughter cells, each of which receives one of the two sets of DNA genes.

Nucleoli and Formation of Ribosomes

The nuclei of most cells contain one or more highly staining structures called nucleoli. The nucleolus does not have a limiting membrane. Instead, it is simply an accumulation of large amounts of RNA and proteins of the types found in ribosomes. The nucleolus becomes considerably enlarged when the cell is actively synthesizing proteins. Formation of the nucleoli (and of the ribosomes in the cytoplasm outside the nucleus) begins in the nucleus.

Filament and Tubular Structures of the Cell

noreply@blogger.com (Anonymous) — Thu, 22 Aug 2013 09:19:00 +0000

Filament and Tubular Structures of the Cell

The fibrillar proteins of the cell are usually organized into filaments

or tubules. These originate as precursor protein molecules synthesized by ribosomes in the cytoplasm. The precursor molecules then polymerize to form filaments.

Mitochondria

noreply@blogger.com (Anonymous) — Thu, 22 Aug 2013 09:18:00 +0000

Mitochondria:

The mitochondria also called the “power houses” of the cell. Without them, cells would be unable to extract enough energy from the nutrients, and essentially all cellular functions would cease. Mitochondria are present in all areas of each cell’s cytoplasm, but the total number per cell

varies from less than a hundred up to several thousand, depending on the amount of energy required by the cell. Further, the mitochondria are concentrated in those portions of the cell that are responsible for the major share of its energy metabolism. They are also variable in size and

shape. it composed mainly of two lipid bilayer –protein membranes:

an outer membrane and an inner membrane. Many infoldings of the inner membrane form shelves onto which oxidative enzymes are attached; the inner cavity of the mitochondrion is filled with a matrix that contains large quantities of dissolved enzymes that are necessary for extracting energy from nutrients.

These enzymes operate in association with the oxidative enzymes on the shelves to cause oxidation of the nutrients, thereby forming carbon dioxide and water and at the same time releasing energy. The liberated energy is used to synthesize a “high-energy” substance called adenosine triphosphate (ATP).ATP is then transported out of the mitochondrion, and it diffuses throughout the cell to release its own energy wherever it is

needed for performing cellular function. Mitochondria are self replicative, which means that one mitochondrion can form a second one, a third one, and so on, whenever there is a need in the cell for increased amounts of ATP. Indeed, the mitochondria contain DNA similar to that found in the cell nucleus. The DNA of the mitochondrion plays a role in controlling replication of the mitochondrion itself.

Secretory Vesicles

noreply@blogger.com (Anonymous) — Thu, 22 Aug 2013 09:17:00 +0000

Secretory Vesicles:

One of the important functions of many cells is secretion of special chemical substances. Almost all such secretory substances are formed by the endoplasmic reticulum–G

olgi apparatus system and are then released from the Golgi apparatus into the cytoplasm in the form of storage vesicles called secretory vesicles or secretory granules.

Lysosomes & Peroxisomes

noreply@blogger.com (Anonymous) — Thu, 22 Aug 2013 09:17:00 +0000

Lysosomes: Lysosomes are vesicular organelles that form by breaking off from the Golgi apparatus and then dispersing throughout the cytoplasm. The lysosomes provide an intracellular digestive system that allows the cell to digest:

(1) Damaged cellular structures.

(2) Food particles that have been ingested by the cell.

(3) Unwanted matter such as bacteria.

It is surrounded by a typical lipid bilayer membrane and is filled with large numbers of small granules, which are protein aggregates of as many as 40 different hydrolase (digestive) enzymes. A hydrolytic enzyme is capable of splitting an organic compound into two or more parts.

Peroxisomes: Peroxisomes are similar physically to lysosomes, but they are different in two important ways:

First, they are believed to be formed by self-replication (or perhaps by budding off from the smooth endoplasmic reticulum) rather than from the Golgi apparatus.

Second, they contain oxidases rather than hydrolases. Several of the oxidases are capable of combining oxygen with hydrogen ions derived from different intracellular chemicals to form hydrogen peroxide (H2O2). Hydrogen peroxide is a highly oxidizing substance and is used in association with catalase, another oxidase enzyme present in large quantities in peroxisomes, to oxidize many substances that might otherwise be poisonous to the cell.