Test Review Chapters 27 and 17. Mammary Glands Modified sweat glands consisting of 15–25 lobes Areola: pigmented skin surrounding the nipple Suspensory

Test Review

Chapters 27 and 17

Mammary Glands

• Modified sweat glands consisting of 15–25 lobes

• Areola: pigmented skin surrounding the nipple• Suspensory ligaments: attach the breast to

underlying muscle • Lobules within lobes contain glandular alveoli

that produce milk

Breast Cancer: Detection and Treatment

• 70% of women with breast cancer have no known risk factors

• Early detection via self-examination and mammography

• Treatment depends upon the characteristics of the lesion:– Radiation, chemotherapy, and surgery followed by

irradiation and chemotherapy

Breast Cancer• Usually arises from the epithelial cells of small

ducts• Risk factors include:

– Early onset of menstruation and late menopause– No pregnancies or first pregnancy late in life– Family history of breast cancer

• 10% are due to hereditary defects, including mutations to the genes BRCA1 and BRCA2

Oogenesis

• Production of female gametes• Begins in the fetal period

– Oogonia (2n ovarian stem cells) multiply by mitosis and store nutrients

– Primary oocytes develop in primordial follicles – Primary oocytes begin meiosis but stall in

prophase I

Ovaries (oogenesis)

• Follicle– Immature egg (oocyte) surrounded by

• Follicle cells (one cell layer thick) • Granulosa cells (when more than one layer is present)

Follicles• Several stages of development

– Primordial follicle: squamous-like follicle cells + oocyte

– Primary follicle: cuboidal or columnar follicle cells + oocyte

– Secondary follicle: two or more layers of granulosa cells + oocyte

– Late secondary follicle: contains fluid-filled space between granulosa cells; coalesces to form a central antrum

Ovaries

• Vesicular (Graafian) follicle– Fluid-filled antrum forms; follicle bulges from

ovary surface

• Ovulation– Ejection of the oocyte from the ripening follicle

• Corpus luteum develops from ruptured follicle after ovulation

Figure 27.11a

Medulla

Tunicaalbuginea

Germinalepithelium

Cortex

Oocyte Granulosa cellsLate secondary follicle

Antrum

Primaryfollicles

Oocyte

Zonapellucida

Thecafolliculi

Ovulatedoocyte

Mesovarium andblood vessels

Vesicular(Graafian)follicle

Coronaradiata

Developingcorpus luteum

Corpus luteum

Ovarianligament

Degenerating corpusluteum (corpus albicans)

(a) Diagrammatic view of an ovary sectioned to reveal the follicles in its interior

Oogenesis

• Each month after puberty, a few primary oocytes are activated

• One is selected each month to resume meiosis I

• Result is two haploid cells – Secondary oocyte– First polar body

Oogenesis

• The secondary oocyte arrests in metaphase II and is ovulated

• If penetrated by sperm the second oocyte completes meiosis II, yielding– Ovum (the functional gamete)– Second polar body

Figure 27.17

Meiotic events Follicle developmentin ovaryBefore birth

Infancy andchildhood(ovary inactive)

Primary oocyte

Primary oocyte (stillarrested in prophase I)

Vesicular (Graafian)follicle

Primary follicle

Primordial follicle

Primordial follicle

Oocyte

Ovulated secondaryoocyte

In absence offertilization, ruptured follicle becomes a corpus luteum andultimately degenerates.Degenating

corpus luteum

Secondary follicle

Primary oocyte(arrested in prophase I;present at birth)

Oogonium (stem cell)

Each month frompuberty to menopause

Meiosis I (completed by one primary oocyte each month in response to LH surge)

First polar body

Mitosis

Growth

Meiosis II of polarbody (may or may not occur)

Polar bodies(all polar bodiesdegenerate)

OvumSecondpolar body

Meiosis IIcompleted(only if spermpenetration occurs)

SpermOvulation

Secondary oocyte(arrested in metaphase II)

Follicle cells

Spindle

Ovarian Cycle

• Monthly series of events associated with the maturation of an egg

• Two consecutive phases (in a 28-day cycle)– Follicular phase: period of follicle growth (days 1–

14)– Ovulation occurs midcycle– Luteal phase: period of corpus luteum activity

(days 14–28)

Ovulation

• Ovary wall ruptures and expels the secondary oocyte with its corona radiata

• Mittelschmerz: twinge of pain sometimes felt at ovulation

• 1–2% of ovulations release more than one secondary oocyte, which, if fertilized, results in fraternal twins

Luteal Phase

• Ruptured follicle collapses• Granulosa cells and internal thecal cells form

corpus luteum• Corpus luteum secretes progesterone and

estrogen

Luteal Phase

• If no pregnancy, the corpus luteum degenerates into a corpus albicans in 10 days

• If pregnancy occurs, corpus luteum produces hormones until the placenta takes over at about 3 months

Establishing the Ovarian Cycle

• During childhood, ovaries grow and secrete small amounts of estrogens that inhibit the hypothalamic release of GnRH

• As puberty nears, GnRH is released; FSH and LH are released by the pituitary, and act on the ovaries

• These events continue until an adult cyclic pattern is achieved and menarche occurs


• During childhood, until puberty– Ovaries secrete small amounts of estrogens– Estrogen inhibits release of GnRH


• At puberty– Leptin from adipose tissue decreases the estrogen

inhibition – GnRH, FSH, and LH are released– In about four years, an adult cyclic pattern is

achieved and menarche occurs

Hormonal Interactions During a 28-Day Ovarian Cycle

• Day 1: GnRH release of FSH and LH– FSH and LH growth of several follicles, and

estrogen release– estrogen levels

• Inhibit the release of FSH and LH• Stimulate synthesis and storage of FSH and LH • Enhance further estrogen output


• Estrogen output by the vesicular follicle increases

• High estrogen levels have a positive feedback effect on the pituitary at midcycle

• Sudden LH surge at day 14


• Effects of LH surge– Completion of meiosis I (secondary oocyte

continues on to metaphase II)– Triggers ovulation– Transforms ruptured follicle into corpus luteum


• Functions of corpus luteum– Produces inhibin, progesterone, and estrogen– These hormones inhibit FSH and LH release

• Declining LH and FSH ends luteal activity and inhibits follicle development


• Days 26–28: corpus luteum degenerates and ovarian hormone levels drop sharply – Ends the blockade of FSH and LH– The cycle starts anew

Figure 27.19

Hypothalamus

Late follicular andluteal phases

1

1

2 2

2

3

4

5

5

6

8

8

7 Slightlyelevated estrogen and rising inhibin levels.

Positivefeedback exerted by large inestrogen output.

Mature follicleCorpus luteum

Ovulatedsecondaryoocyte

Rupturedfollicle

LH surgeProgesteroneEstrogenInhibin

Hypothalamus

Early and midfollicular phases

Travels viaportal blood

Granulosacells

Inhibin

Androgens

Convertandrogens toestrogens

Thecalcells

Anterior pituitary

GnRH

FSH LH

Figure 27.20a

(a) Fluctuation of gonadotropin levels: Fluctuating levels of pituitary gonadotropins (follicle-stimulating hormone and luteinizing hormone) in the blood regulate the events of the ovarian cycle.

FSH

LH

Figure 27.20b

(b) Ovarian cycle: Structural changes in the ovarian follicles during the ovarian cycle are correlated with (d) changes in the endometrium of the uterus during the uterine cycle.

Primaryfollicle

Secondaryfollicle

Vesicularfollicle

Ovulation

Corpusluteum Degenerating

corpus luteum

Follicularphase

Ovulation(Day 14)

Lutealphase

Uterine (Menstrual) Cycle

• Cyclic changes in endometrium in response to ovarian hormones

• Three phases 1. Days 1–5: menstrual phase2. Days 6–14: proliferative (preovulatory) phase3. Days 15–28: secretory (postovulatory) phase

(constant 14-day length)

Uterine Cycle

• Menstrual phase– Ovarian hormones are at their lowest levels– Gonadotropins are beginning to rise– Stratum functionalis is shed and the menstrual

flow occurs

Uterine Cycle

• Proliferative phase– Estrogen levels prompt generation of new

functional layer and increased synthesis of progesterone receptors in endometrium

– Glands enlarge and spiral arteries increase in number

Uterine Cycle

• Secretory phase– Progesterone levels prompt

• Further development of endometrium• Glandular secretion of glycogen• Formation of the cervical mucus plug

Figure 27.20c

(c) Fluctuation of ovarian hormone levels: Fluctuating levels of ovarian hormones (estrogens and progesterone) cause the endometrial changes of the uterine cycle. The high estrogen levels are also responsible for the LH/FSH surge in (a).

Progesterone

Estrogens

Endometrium

• Stratum functionalis (functional layer)– Changes in response to ovarian hormone cycles– Is shed during menstruation

• Stratum basalis (basal layer)– Forms new functionalis after menstruation – Unresponsive to ovarian hormones

Figure 27.20d

(d) The three phases of the uterine cycle: • Menstrual: Shedding of the functional layer of the endometrium. • Proliferative: Rebuilding of the functional layer of the endometrium. • Secretory: Begins immediately after ovulation. Enrichment of the blood supply and glandular secretion of nutrients prepare the endometrium to receive an embryo.Both the menstrual and proliferative phases occur before ovulation, and together they correspond to the follicular phase of the ovarian cycle. Thesecretory phase corresponds in time to the luteal phase of the ovarian cycle.

Menstrualphase

Menstrualflow

Endometrialglands

Blood vessels

Functional layer

Basal layer

Proliferativephase

Secretoryphase

Days

Uterine Cycle• If fertilization does not occur

– Corpus luteum degenerates– Progesterone levels fall– Spiral arteries kink and spasm– Endometrial cells begin to die– Spiral arteries constrict again, then relax and open

wide– Rush of blood fragments weakened capillary beds

and the functional layer sloughs

Effects of Estrogens

• Promote oogenesis and follicle growth in the ovary

• Exert anabolic effects on the female reproductive tract

• Support the rapid but short-lived growth spurt at puberty


• Induce secondary sex characteristics– Growth of the breasts– Increased deposit of subcutaneous fat (hips and

breasts)– Widening and lightening of the pelvis


• Metabolic effects– Maintain low total blood cholesterol and high HDL

levels– Facilitates calcium uptake

Effects of Progesterone

• Progesterone works with estrogen to establish and regulate the uterine cycle

• Effects of placental progesterone during pregnancy– Inhibits uterine motility– Helps prepare the breasts for lactation

Hormonal Regulation of Male Reproductive Function

• A sequence of hormonal regulatory events involving the hypothalamus, anterior pituitary gland, and the testes – The hypothalamic-pituitary-gonadal (HPG) axis

HPG Axis1. Hypothalamus releases gonadotropin-

releasing hormone (GnRH) 2. GnRH stimulates the anterior pituitary to

secrete FSH and LH3. FSH causes sustentacular cells to release

androgen-binding protein (ABP), which makes spermatogenic cell receptive to testosterone

4. LH stimulates interstitial cells to release testosterone

HPG Axis

5. Testosterone is the final trigger for spermatogenesis

6. Feedback inhibition on the hypothalamus and pituitary results from– Rising levels of testosterone– Inhibin (released when sperm count is high)

Figure 27.9

Anteriorpituitary

Inhibin

GnRH

Testosterone

Via portalblood

Interstitialcells

SustentacularcellSpermatogeniccells

Seminiferoustubule

Somatic andpsychologicaleffects atother bodysites

LHFSH

1

2

2

3 4

5

6

78

Stimulates

Inhibits

Mechanism and Effects of Testosterone Activity

• Testosterone– Synthesized from cholesterol– Transformed to exert its effects on some target

cells• Dihydrotestosterone (DHT) in the prostate• Estrogen in some neurons in the brain

Mechanism and Effects of Testosterone Activity

• Prompts spermatogenesis• Targets all accessory organs; deficiency leads

to atrophy• Has multiple anabolic effects throughout the

body• Is the basis of the sex drive (libido) in males

Male Secondary Sex Characteristics

• Features induced in the nonreproductive organs by male sex hormones (mainly testosterone)– Appearance of pubic, axillary, and facial hair– Enhanced growth of the chest and deepening of

the voice– Skin thickens and becomes oily– Bones grow and increase in density– Skeletal muscles increase in size and mass

Functions of Blood

1. Distribution of– O2 and nutrients to body cells

– Metabolic wastes to the lungs and kidneys for elimination

– Hormones from endocrine organs to target organs

Functions of Blood

2. Regulation of– Body temperature by absorbing and distributing

heat– Normal pH using buffers– Adequate fluid volume in the circulatory system

Functions of Blood

3. Protection against– Blood loss

• Plasma proteins and platelets initiate clot formation– Infection

• Antibodies• Complement proteins• WBCs defend against foreign invaders

Blood Plasma

• 90% water• Proteins are mostly produced by the liver

– 60% albumin– 36% globulins– 4% fibrinogen

Blood Plasma

• Nitrogenous by-products of metabolism—lactic acid, urea, creatinine

• Nutrients—glucose, carbohydrates, amino acids

• Electrolytes—Na+, K+, Ca2+, Cl–, HCO3–

• Respiratory gases—O2 and CO2

• Hormones

Erythrocytes

• Biconcave discs, anucleate, essentially no organelles

• Filled with hemoglobin (Hb) for gas transport• Contain the plasma membrane protein

spectrin and other proteins– Provide flexibility to change shape as necessary

• Are the major factor contributing to blood viscosity

Erythrocyte Function

• Hemoglobin structure– Protein globin: two alpha and two beta chains– Heme pigment bonded to each globin chain

• Iron atom in each heme can bind to one O2 molecule

• Each Hb molecule can transport four O2

Erythrocytes

• Structural characteristics contribute to gas transport – Biconcave shape—huge surface area relative to

volume– >97% hemoglobin (not counting water)– No mitochondria; ATP production is anaerobic; no

O2 is used in generation of ATP• A superb example of complementarity of

structure and function!

Hematopoiesis

• Hematopoiesis (hemopoiesis): blood cell formation – Occurs in red bone marrow of axial skeleton,

girdles and proximal epiphyses of humerus and femur

Hematopoiesis

• Hemocytoblasts (hematopoietic stem cells)– Give rise to all formed elements– Hormones and growth factors push the cell

toward a specific pathway of blood cell development

• New blood cells enter blood sinusoids

Erythropoiesis

– Phases in development1. Ribosome synthesis 2. Hemoglobin accumulation 3. Ejection of the nucleus and formation of reticulocytes

– Reticulocytes then become mature erythrocytes

Regulation of Erythropoiesis

• Too few RBCs leads to tissue hypoxia• Too many RBCs increases blood viscosity• Balance between RBC production and

destruction depends on– Hormonal controls – Adequate supplies of iron, amino acids, and B

vitamins

Hormonal Control of Erythropoiesis

• Erythropoietin (EPO)– Direct stimulus for erythropoiesis – Released by the kidneys in response to hypoxia

Hormonal Control of Erythropoiesis

• Effects of EPO– More rapid maturation of committed bone

marrow cells– Increased circulating reticulocyte count in 1–

2 days

• Testosterone also enhances EPO production, resulting in higher RBC counts in males

Dietary Requirements for Erythropoiesis

• Nutrients—amino acids, lipids, and carbohydrates• Iron

– Stored in Hb (65%), the liver, spleen, and bone marrow– Stored in cells as ferritin and hemosiderin– Transported loosely bound to the protein transferrin

• Vitamin B12 and folic acid—necessary for DNA synthesis for cell division

Figure 17.7

Low O2 levels in blood stimulate kidneys to produce erythropoietin.

1

Erythropoietin levels risein blood.2

Erythropoietin and necessaryraw materials in blood promoteerythropoiesis in red bone marrow.

3

Aged and damagedred blood cells areengulfed by macrophagesof liver, spleen, and bonemarrow; the hemoglobinis broken down.

5

New erythrocytesenter bloodstream;function about 120 days.

4

Raw materials aremade available in bloodfor erythrocyte synthesis.

6

Hemoglobin

Aminoacids

Globin

Iron is bound totransferrin and releasedto blood from liver asneeded for erythropoiesis.

Food nutrients,including amino acids,Fe, B12, and folic acid,are absorbed fromintestine and enterblood.

Heme

Circulation

Iron storedas ferritin,hemosiderin

Bilirubin

Bilirubin is picked up from bloodby liver, secreted into intestine inbile, metabolized to stercobilin bybacteria, and excreted in feces.

Causes of Anemia

1. Insufficient erythrocytes– Hemorrhagic anemia: acute or chronic loss of

blood– Hemolytic anemia: RBCs rupture prematurely– Aplastic anemia: destruction or inhibition of red

bone marrow

Causes of Anemia

2. Low hemoglobin content– Iron-deficiency anemia

• Secondary result of hemorrhagic anemia or• Inadequate intake of iron-containing foods or• Impaired iron absorption

Causes of Anemia

– Pernicious anemia• Deficiency of vitamin B12

• Lack of intrinsic factor needed for absorption of B12

• Treated by intramuscular injection of B12 or application of Nascobal

Causes of Anemia

– Sickle-cell anemia• Defective gene codes for abnormal hemoglobin (HbS)• Causes RBCs to become sickle shaped in low-oxygen

situations

Figure 17.8

1 2 3 4 5 6 7 146

1 2 3 4 5 6 7 146

(a) Normal erythrocyte has normal hemoglobin amino acid sequence in the beta chain.

(b) Sickled erythrocyte results from a single amino acid change in the beta chain of hemoglobin.

Erythrocyte Disorders

• Polycythemia: excess of RBCs that increase blood viscosity

• Results from:– Polycythemia vera—bone marrow cancer– Secondary polycythemia—when less O2 is

available (high altitude) or when EPO production increases

– Blood doping

Leukocytes

• Make up <1% of total blood volume• Can leave capillaries via diapedesis• Move through tissue spaces by ameboid

motion and positive chemotaxis• Leukocytosis: WBC count over 11,000/mm3

– Normal response to bacterial or viral invasion

Granulocytes

• Granulocytes: neutrophils, eosinophils, and basophils– Cytoplasmic granules stain specifically with

Wright’s stain– Larger and shorter-lived than RBCs– Lobed nuclei– Phagocytic

Neutrophils

• Most numerous WBCs• Polymorphonuclear leukocytes (PMNs)• Fine granules take up both acidic and basic

dyes• Give the cytoplasm a lilac color• Granules contain hydrolytic enzymes or

defensins • Very phagocytic—“bacteria slayers”

Eosinophils

• Red-staining, bilobed nuclei • Red to crimson (acidophilic) coarse, lysosome-

like granules• Digest parasitic worms that are too large to be

phagocytized• Modulators of the immune response

Basophils

• Rarest WBCs• Large, purplish-black (basophilic) granules

contain histamine– Histamine: an inflammatory chemical that acts as

a vasodilator and attracts other WBCs to inflamed sites

• Are functionally similar to mast cells

Agranulocytes

• Agranulocytes: lymphocytes and monocytes– Lack visible cytoplasmic granules– Have spherical or kidney-shaped nuclei

Lymphocytes

• Large, dark-purple, circular nuclei with a thin rim of blue cytoplasm

• Mostly in lymphoid tissue; few circulate in the blood

• Crucial to immunity

Lymphocytes

• Two types – T cells act against virus-infected cells and tumor

cells– B cells give rise to plasma cells, which produce

antibodies

Monocytes

• The largest leukocytes• Abundant pale-blue cytoplasm• Dark purple-staining, U- or kidney-shaped

nuclei

Monocytes

• Leave circulation, enter tissues, and differentiate into macrophages– Actively phagocytic cells; crucial against viruses,

intracellular bacterial parasites, and chronic infections

• Activate lymphocytes to mount an immune response

Table 17.2 (1 of 2)

Table 17.2 (2 of 2)

Leukopoiesis

• Production of WBCs• Stimulated by chemical messengers from

bone marrow and mature WBCs– Interleukins (e.g., IL-1, IL-2)– Colony-stimulating factors (CSFs) named for the

WBC type they stimulate (e.g., granulocyte-CSF stimulates granulocytes)

• All leukocytes originate from hemocytoblasts

Leukocyte Disorders• Leukopenia

– Abnormally low WBC count—drug induced• Leukemias

– Cancerous conditions involving WBCs– Named according to the abnormal WBC clone involved– Myelocytic leukemia involves myeloblasts– Lymphocytic leukemia involves lymphocytes

• Acute leukemia involves blast-type cells and primarily affects children

• Chronic leukemia is more prevalent in older people

Platelets

• Small fragments of megakaryocytes• Formation is regulated by thrombopoietin• Blue-staining outer region, purple granules• Granules contain serotonin, Ca2+, enzymes,

ADP, and platelet-derived growth factor (PDGF)

Platelets• Form a temporary platelet plug that helps seal breaks in

blood vessels• Circulating platelets are kept inactive and mobile by NO

and prostacyclin from endothelial cells of blood vessels

Hemostasis

• Fast series of reactions for stoppage of bleeding

1. Vascular spasm 2. Platelet plug formation3. Coagulation (blood clotting)

Vascular Spasm

• Vasoconstriction of damaged blood vessel• Triggers

– Direct injury– Chemicals released by endothelial cells and

platelets – Pain reflexes

Platelet Plug Formation

• Positive feedback cycle– At site of blood vessel injury, platelets

• Stick to exposed collagen fibers with the help of von Willebrand factor, a plasma protein

• Swell, become spiked and sticky, and release chemical messengers

– ADP causes more platelets to stick and release their contents

– Serotonin and thromboxane A2 enhance vascular spasm and more platelet aggregation

Figure 17.13

Collagenfibers

Platelets

Fibrin

Step Vascular spasm• Smooth muscle contracts, causing vasoconstriction.

Step Platelet plugformation

• Injury to lining of vessel exposes collagen fibers; platelets adhere.

• Platelets release chemicals that make nearby platelets sticky; platelet plug forms.

Step Coagulation• Fibrin forms a mesh that traps red blood cells and platelets, forming the clot.

1

2

3

Coagulation

• Three phases of coagulation1. Prothrombin activator is formed (intrinsic and

extrinsic pathways)2. Prothrombin is converted into thrombin3. Thrombin catalyzes the joining of fibrinogen to

form a fibrin mesh

Figure 17.14 (1 of 2)

Vessel endothelium ruptures,exposing underlying tissues(e.g., collagen)

PF3

released byaggregated

platelets

XII

XI

IX

XIIa

Ca2+

Ca2+

XIa

IXa

Intrinsic pathwayPhase 1Tissue cell traumaexposes blood to

Platelets cling and theirsurfaces provide sites formobilization of factors

Extrinsic pathway

Tissue factor (TF)

VII

VIIa

VIII

VIIIa

Ca2+

X

Xa

Prothrombinactivator

PF3

TF/VIIa complexIXa/VIIIa complex

V

Va

Figure 17.14 (2 of 2)

Ca2+

Phase 2

Phase 3

Prothrombinactivator

Prothrombin (II)

Thrombin (IIa)

Fibrinogen (I)(soluble)

Fibrin(insolublepolymer) XIII

XIIIa

Cross-linkedfibrin mesh

Coagulation Phase 1: Two Pathways to Prothrombin Activator

• Initiated by either the intrinsic or extrinsic pathway (usually both)– Triggered by tissue-damaging events– Involves a series of procoagulants– Each pathway cascades toward factor X

• Factor X complexes with Ca2+, PF3, and factor V to form prothrombin activator

Coagulation Phase 1: Two Pathways to Prothrombin Activator

• Intrinsic pathway– Is triggered by negatively charged surfaces

(activated platelets, collagen, glass)– Uses factors present within the blood (intrinsic)

• Extrinsic pathway– Is triggered by exposure to tissue factor (TF) or

factor III (an extrinsic factor)– Bypasses several steps of the intrinsic pathway, so

is faster

Coagulation Phase 2: Pathway to Thrombin

• Prothrombin activator catalyzes the transformation of prothrombin to the active enzyme thrombin

Coagulation Phase 3: Common Pathway to the Fibrin Mesh

• Thrombin converts soluble fibrinogen into fibrin• Fibrin strands form the structural basis of a clot• Fibrin causes plasma to become a gel-like trap for

formed elements • Thrombin (with Ca2+) activates factor XIII which:

– Cross-links fibrin– Strengthens and stabilizes the clot

Clot Retraction

• Actin and myosin in platelets contract within 30–60 minutes

• Platelets pull on the fibrin strands, squeezing serum from the clot

Clot Repair

• Platelet-derived growth factor (PDGF) stimulates division of smooth muscle cells and fibroblasts to rebuild blood vessel wall

• Vascular endothelial growth factor (VEGF) stimulates endothelial cells to multiply and restore the endothelial lining

Fibrinolysis

• Begins within two days• Plasminogen in clot is converted to plasmin by

tissue plasminogen activator (tPA), factor XII and thrombin

• Plasmin is a fibrin-digesting enzyme

Factors Limiting Clot Growth or Formation

• Two homeostatic mechanisms prevent clots from becoming large– Swift removal and dilution of clotting factors – Inhibition of activated clotting factors

Inhibition of Clotting Factors

• Most thrombin is bound to fibrin threads, and prevented from acting elsewhere

• Antithrombin III, protein C, and heparin inactivate thrombin and other procoagulants

• Heparin, another anticoagulant, also inhibits thrombin activity

Factors Preventing Undesirable Clotting

• Platelet adhesion is prevented by– Smooth endothelial lining of blood vessels– Antithrombic substances nitric oxide and

prostacyclin secreted by endothelial cells– Vitamin E quinine, which acts as a potent

anticoagulant

Disorders of Hemostasis

• Thromboembolytic disorders: undesirable clot formation

• Bleeding disorders: abnormalities that prevent normal clot formation

Thromboembolytic Conditions

• Thrombus: clot that develops and persists in an unbroken blood vessel– May block circulation, leading to tissue death

• Embolus: a thrombus freely floating in the blood stream– Pulmonary emboli impair the ability of the body to

obtain oxygen– Cerebral emboli can cause strokes

Thromboembolytic Conditions

• Prevented by– Aspirin

• Antiprostaglandin that inhibits thromboxane A2– Heparin

• Anticoagulant used clinically for pre- and postoperative cardiac care

– Warfarin• Used for those prone to atrial fibrillation

Bleeding Disorders

• Thrombocytopenia: deficient number of circulating platelets– Petechiae appear due to spontaneous,

widespread hemorrhage – Due to suppression or destruction of bone

marrow (e.g., malignancy, radiation)– Platelet count <50,000/mm3 is diagnostic – Treated with transfusion of concentrated platelets

Bleeding Disorders

• Impaired liver function– Inability to synthesize procoagulants – Causes include vitamin K deficiency, hepatitis, and

cirrhosis– Liver disease can also prevent the liver from

producing bile, impairing fat and vitamin K absorption

Bleeding Disorders• Hemophilias include several similar hereditary bleeding

disorders – Hemophilia A: most common type (77% of all cases); due

to a deficiency of factor VIII– Hemophilia B: deficiency of factor IX– Hemophilia C: mild type; deficiency of factor XI

• Symptoms include prolonged bleeding, especially into joint cavities

• Treated with plasma transfusions and injection of missing factors

Transfusions

• Whole-blood transfusions are used when blood loss is substantial

• Packed red cells (plasma removed) are used to restore oxygen-carrying capacity

• Transfusion of incompatible blood can be fatal

Human Blood Groups

• RBC membranes bear 30 types glycoprotein antigens that are– Perceived as foreign if transfused blood is

mismatched– Unique to each individual – Promoters of agglutination and are called

agglutinogens • Presence or absence of each antigen is used

to classify blood cells into different groups

Blood Groups

• Humans have 30 varieties of naturally occurring RBC antigens

• Antigens of the ABO and Rh blood groups cause vigorous transfusion reactions

• Other blood groups (MNS, Duffy, Kell, and Lewis) are usually weak agglutinogens

ABO Blood Groups

• Types A, B, AB, and O• Based on the presence or absence of two

agglutinogens (A and B) on the surface of the RBCs

• Blood may contain anti-A or anti-B antibodies (agglutinins) that act against transfused RBCs with ABO antigens not normally present

• Anti-A or anti-B form in the blood at about 2 months of age

Table 17.4

Rh Blood Groups

• There are 45 different Rh agglutinogens (Rh factors)

• C, D, and E are most common• Rh+ indicates presence of D

Rh Blood Groups

• Anti-Rh antibodies are not spontaneously formed in Rh– individuals

• Anti-Rh antibodies form if an Rh– individual receives Rh+ blood

• A second exposure to Rh+ blood will result in a typical transfusion reaction

Homeostatic Imbalance: Hemolytic Disease of the Newborn

• Also called erythroblastosis fetalis• Rh– mother becomes sensitized when

exposure to Rh+ blood causes her body to synthesize anti-Rh antibodies

• Anti-Rh antibodies cross the placenta and destroy the RBCs of an Rh+ baby

Homeostatic Imbalance: Hemolytic Disease of the Newborn

• The baby can be treated with prebirth transfusions and exchange transfusions after birth

• RhoGAM serum containing anti-Rh can prevent the Rh– mother from becoming sensitized

Transfusion Reactions• Occur if mismatched blood is infused• Donor’s cells

– Are attacked by the recipient’s plasma agglutinins– Agglutinate and clog small vessels– Rupture and release free hemoglobin into the

bloodstream • Result in

– Diminished oxygen-carrying capacity– Hemoglobin in kidney tubules and renal failure

Blood Typing

• When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens

• Positive reactions indicate agglutination

ABO Blood Typing

Blood Type Being Tested

RBC Agglutinogens

Serum Reaction

Anti-A Anti-B

AB A and B + +

B B – +

A A + –

O None – –

Figure 17.16

SerumAnti-A

RBCs

Anti-B

Type AB (containsagglutinogens A and B;agglutinates with bothsera)

Blood being tested

Type A (containsagglutinogen A;agglutinates with anti-A)

Type B (containsagglutinogen B;agglutinates with anti-B)

Type O (contains noagglutinogens; does notagglutinate with eitherserum)

Documents

Test Review Chapters 27 and 17. Mammary Glands Modified sweat glands consisting of 15–25 lobes Areola: pigmented skin surrounding the nipple Suspensory