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PLACENTA & MEMBRANES.pptx
The document covers an in-depth overview of the placenta and fetal membranes, including their structures, functions, and developmental stages. It details placental physiology, including blood flow dynamics and the role of the placenta in nutrient transfer, endocrine function, and immune defense. Additionally, it addresses abnormalities associated with the placenta, the composition and clinical significance of amniotic fluid, and describes the umbilical cord's structure and function.
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PLACENTA & MEMBRANES.pptx
- 1. PLACENTA & MEMBRANES MODERATOR:Dr. Sana Ansari PRESENTER: Dr. Rahul Shah PGY1 Department of Obstetrics & Gynaecology 1/9/2024
- 2. OUTLINES • PLACENTA &its DEVELOPMENT • STRUCTURES • FUNCTIONS • PLACENTAL PATHOLOGY • FUNCTIONS • FETAL MEMBRANES • AMNIOTIC FLUID 1/9/2024
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- 4. DEVELOPMENT • Formed by2 sources. FETAL SOURCES: Chorion Frondosom MATERNAL SOURCES: Decidua Basalis 1/9/2024
- 5. 1/9/2024 • DAY 11:Intersitial implantation completed • DAY 13: stem villi developed from trabeculae which connect chorionic plate with basal plate • Primary, secondary and tertiary villi formed from stem villi • DAY 21: Arterial-capillary-venous system in mesenchymal core of each villi completed
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- 8. PLACENTA AT TERM •Diameter: 15-20 cm • Thickness: 3 cm at the center • Weight: 500gms (1:6) • Occupies 30% of uterine wall • TWO SURFACES: Fetal and Maternal and a peripheral margin 1/9/2024
- 9. FETAL SURFACE • Chorionicplate • Covered by smooth and glistening amnion with umbilical cord attached at or near center • Branches of umbilical vessels are visible beneath the amnion as they radiate from the insertion of cord. • Amnion can be peeled off from the chorion except for the center • 4/5 of placenta is of fetal origin 1/9/2024
- 10. MATERNAL SURFACE • BasalPlate is rough and spongy • Dull red color • Remnant of decidua basalis may be visible ( thin grayish and shaggy) • Lobes or cotyledons 15-20 • Numerous grayish spots: deposition of calcium • Less than 1/5th • Only the decidua basalis and the blood in intervillous space are of maternal origin 1/9/2024
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- 12. MARGIN • Peripheral Margin:limited by fused basal and chorionic plate • Continuous with chorion laeve and amnion • Attachment • Due to anchoring villi connecting chorionic plate with basal plate and also by fused decidua capsularis and vera with the chorion leave at the margin • Usually upper body of uterus encroaching fundus (anterior or posterior wall) • Separation • After birth of baby • Line of separation is through the decidua spongiosum 1/9/2024
- 13. STRUCTURES • AMNIOTIC MEMBRANE:single layer, cubicle epithelium loosely attached to the adjacent chorionic plate. • CHORIONIC PLATE: From within outward it consists of Primitive mesenchymal tissue containing branches of umbilical vessels, layer of cytotrophoblast and syncyttiotrophoblast. The stem villi arise from this plate. • BASAL PLATE: Part of spongy layer of decidua basalis, Nitabuch layer of fibrinoid degeneration of outer syncytiotrophoblast at the junction of cytotrophoblast, cytotrophoblastic shell and syncytiotrophoblast 1/9/2024
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- 17. PLACENTAL CIRCULATION 1/9/2024 UTEROPLACENTAL CIRCULATIONFETOPLACENTAL CIRCULATION Between Mother and Placenta Fetus and placenta Present in Intervillious Space Villi Formed by Day 15 Day 17 Via Spiral Arteries Umbilical Artery No. of spiral arteries that open in internal space: 120-200 O2 saturation of interval space: 65-75% Partial pressure in interval space: 30-35% Uteroplacental blood flow at term: 500- 750ml/min Uterine blood flow at term: 750ml/min Fetoplacental Blood flow at term: 400ml/min Fetal blood flow at term: 125ml/kg Rate of O2 delivery to fetus: 8ml/kg/min
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- 19. PLACENTAL BARRIER (PLACENTALMEMBRANE) 1/9/2024
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- 21. DECIDUAL CHANGES • Thereis an area of fibrinoid degeneration where trophoblast cells (covered with syncytium) meet the decidua. This zone is known as Nitabuch layer. • This layer limits further invasion of the decidua by the trophoblast. The membrane is absent in placenta accreta. 1/9/2024
- 22. PLACENTAL FUNCTIONS • 1.Transfer of nutrients and waste products between the mother and fetus. In this respect it attributes to the following functions: • Respiratory • Excretory • Nutritive • 2. Endocrine function: Placenta is an endocrine gland. It produces both steroid and peptide hormones to maintain pregnancy • 3. Barrier function. • 4. Immunological function. 1/9/2024
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- 24. MECHANISM INVOLVED INPLACENTAL TRANSFER • Bulk flow and solvent drag • Simple diffusion. • Facilitated diffusion. • Active transfer • Endocytosis • Exocytosis • Leakage 1/9/2024
- 25. Respiratory function: • fetalrespiratory movements are observed as early as 11 weeks, there is no gaseous exchange. • Intake of oxygen and output of carbon dioxide take place by simple diffusion across the fetal membrane. • The oxygen supply to the fetus is at the rate of 8 mL/Kg/min and this is achieved with cord blood flow of 165–330 mL/min. 1/9/2024
- 26. Excretory function •Waste productsfrom the fetus such as urea, uric acid, and creatinine are excreted to the maternal blood by simple diffusion 1/9/2024
- 27. Nutritive function: • Glucose:Facilated Diffusion Via GLUT I • Lipids • Amino Acids: Active Transport • Water and Electrolytes: Simple diffusion and Active Transport • Hormones 1/9/2024
- 28. BARRIER FUNCTION • Fetalmembrane has long been considered as a protective barrier to the fetus against noxious agents circulating in the maternal blood. • substances of high molecular weight of more than 500 daltons are held up but there are exceptions. • Antibody and antigens in immunological quantities can traverse across the placental barrier in both directions. The transfer of the larger molecule is probably facilitated by pinocytosis. • Maternal infection during pregnancy by virus (rubella, chickenpox, measles, mumps, poliomyelitis), bacteria (Treponema pallidum, Tubercle bacillus) or protozoa (Toxoplasma gondii, malaria parasites) may be transmitted to the fetus across the so called placental barrier and affect the fetus in utero. 1/9/2024
- 29. IMMUNOLOGICAL FUNCTION • Thefetus & placenta contains paternally determined antigens: but no graft rejection • SP1, EPF, PAPP-A, Steroid & chronic gonadotropin have got some immunosuppressive effect. • Shift of maternal response from cell mediated to humoral (TH1 to TH2) • Decidual NK cells and trophoblast HLA class 1 molecule interact. The cytokine thus derived regulates the invasion of extravillious trophoblastic cells into spiral arteries converted to low resistance and high conductance. 1/9/2024
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- 47. FETAL MEMBRANES • 2LAYERS: OUTER CHORION & INNER CHORION 1/9/2024
- 48. CHORION • It representsthe remnant of chorion laeve and ends at the margin of the placenta. • Thicker than amnion, friable and shaggy on both the sides. • Internally, it is attached to the amnion by loose areolar tissue and remnant of primitive mesenchyme. • Externally, it is covered by vestiges of trophoblastic layer and the decidual cells of the fused decidua capsularis and parietalis which can be distinguished microscopically • Therefore human placenta is a discoid, deciduate, larynthine and haemochorial type 1/9/2024
- 49. AMNION • It isthe inner layer of the fetal membranes. • Its internal surface is smooth and shiny and is in contact with liquor amnii. • The outer surface consists of a layer of connective tissue and is apposed to the similar tissue on the inner aspect of the chorion from which it can be peeled off. • The amnion can also be peeled off from the fetal surface of the placenta except at the insertion of the umbilical cord 1/9/2024
- 50. Functions • :Contribute tothe formation of liquor amnii • Intact membranes prevent ascending uterine infection • Facilitate dilatation of the cervix during labor • Has got enzymatic activities for steroid hormonal metabolism • Rich source of glycerophospholipids containing arachidonic acid — precursor of prostaglandin E2 and F2a. 1/9/2024
- 51. AMNIOTIC CAVITY, AMNIONAND AMNIOTIC FLUID 1/9/2024
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- 53. AMNIOTIC FLUID • ORIGINOF AMNIOTIC FLUID: not well understood. It is probably of mixed maternal and fetal origin. • CIRCULATION: completely changed and replaced in every 3 hours as shown by the clearance of radioactive sodium injected directly into the amniotic cavity. • The presence of lanugo and epithelial scales in the meconium shows that the fluid is swallowed by the fetus and some of it passes from the gut into the fetal plasma • VOLUME: Amniotic fluid, volume is related to gestational age. It measures about 50 mL at 12 weeks, 400 mL at 20 weeks and reaches its peak of 1 liter at 36–38 weeks. Thereafter the amount diminishes, till at term it measures about 600– 800 mL. • As the pregnancy continues post term, further reduction occurs to the extent of about 200 mL at 43 weeks. 1/9/2024
- 54. PHYSICAL FEATURES: • Thefluid is faintly alkaline with low specific gravity of 1.010. • It becomes highly hypotonic to maternal serum at term pregnancy. • An osmolarity of 250 mOsmol/L is suggestive of fetal maturity. • The amniotic fluid’s osmolality falls with advancing gestation. • Color: In early pregnancy, it is colorless but near term it becomes pale straw colored due to the presence of • exfoliated lanugo and epidermal cells from the fetal skin. It may look turbid due to the presence of vernix caseosa. 1/9/2024
- 55. Abnormal color • Deviationof the normal color of the liquor has got clinical significance. • — Meconium stained (green) is suggestive of fetal distress in presentations other than the breech or transverse. • Depending upon the degree and duration of the distress, it may be thin or thick or pea souped (thick with flakes). • Thick with presence of flakes suggests chronic fetal distress. • — Golden color in Rh incompatibility is due to excessive hemolysis of the fetal RBC and production of excess bilirubin. • — Greenish yellow (saffron) in post maturity. • — Dark colored in concealed accidental hemorrhage is due to contamination of blood. • — Dark brown (tobacco juice) amniotic fluid is found in IUD. The dark color is due to frequent presence of old HbA. 1/9/2024
- 56. COMPOSITION • In thefirst half of pregnancy, the composition of the fluid is almost identical to a transudate of plasma. • But in late pregnancy, the composition is very much altered mainly due to contamination of fetal • urinary metabolites. The composition includes—(1) water 98–99% and (2) solid (1–2%). The following are the solid constituents: • (a) Organic: • Protein–0.3 mg% NPN–30 mg% Total lipids–50 mg% • Glucose–20 mg% Uric acid–4 mg% Hormones (Prolactin, insulin and renin) • Urea–30 mg% Creatinine–2 mg% 1/9/2024
- 57. CLINICAL IMPORTANCE: • Studyof the amniotic fluid provides useful information about the well being and also maturity of the fetus. • Intra-amniotic instillation of chemicals is used as method of induction of abortion. • Excess or less volume of liquor amnii is assessed by amniotic fluid index (AFI) • It is measured to diagnose the clinical condition of polyhydramnios or oligohydramnios respectively. • Rupture of the membranes with drainage of liquor is a helpful method in induction of labor 1/9/2024
- 58. THE UMBILICAL CORD:DEVELOPMENT 1/9/2024
- 59. STRUCTURES • Covering epithelium •Wharton’s jelly • Blood vessels • Remnant of the umbilical vesicle (yolk sac) and its vitelline duct • Allantois • Obliterated extraembryonic coelom 1/9/2024
- 60. CHRACTERSTICS • About 40cm in length with an usual variation of 30–100 cm. • diameter is of average 1.5 cm with variation of 1–2.5 cm. • thickness not uniform but presents nodes or swelling at places. • These swellings (false knots) may be due to kinking of the umbilical vessels or local collection Wharton’s jelly. • True knots (1%) are rare. • Long cord may form loop around the neck (20–30%). • The umbilical arteries do not possess an internal elastic lamina but have got well developed muscular coat. These help in effective closure of the arteries due to reflex spasm soon after the birth of the baby. • Both the arteriesand the vein do not possess vasa vasorum. 1/9/2024
- 61. ATTACHMENT • It usuallyattaches to the fetal surface of the placenta somewhere between the center and the edge of the placenta—called eccentric insertion. • The attachment may be central, marginal or even on the chorion laeve at a varying distance away from the margin of the placenta, called velamentous insertion. 1/9/2024
- 62. 1/9/2024 PLACENTA USES INMEDICINE AND COSMETICS
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Editor's Notes
- #4 Discoid because of its shape Hemochorial because of direct contact with chorion with the maternal blood Deciduate because of some maternal tissue is shed at parturition Hemodochorial: where there is continuous inner layer of cytotrophoblast and outer layer of syncitiotrophoblast. Seen in 1st tri Hemomonochorial:later in gestation the inner layer of cytotropjoblast is no longer continuous, by term there are only scattered cells present,
- #5 Exchange coour in intervillious space by chorionic villi Implantation occurs 6-10 days after fertilization
- #6 When the interstitial implantation is completed on 11th day, the blastocyst is surrounded on all sides by lacunar spaces around cords of syncytial cells, called trabeculae. From the trabeculae develops the stem villi on 13th day which connect the chorionic plate with the basal plate. Primary, secondary and tertiary villi are successively developed from the stem villi. Arterio-capillary-venous system in the mesenchymal core of each villus is completed on 21st day. This ultimately makes connection with the intraembryonic vascular system through the body stalk Simultaneously, lacunar spaces become confluent with one another and by 3rd and 4th week, form a multilocular receptacle lined by syncytium and filled with maternal blood. This space becomes the future intervillous space. As the growth of the embryo proceeds, decidua capsularis becomes thinner beginning at 6th week and both the villi and the lacunar spaces in the abembryonic area get obliterated, converting the chorion into chorion laeve. This is, however, compensated by (a) exuberant growth and proliferation of the decidua basalis and (b) enormous and exuberant division and sub-division of the chorionic villi in the embryonic pole (chorion frondosum). These two, i.e. chorion frondosum and the decidua basalis form the discrete placenta. It begins at 6th week and is completed by 12th week (Fig. 3.1). Until the end of the 16th week, the placenta grows both in thickness and circumference due to growth of the chorionic villi with accompanying expansion of the intervillous space. Subsequently, there is little increase in thickness but it increases circumferentially till term. The human hemochorial placenta derived its name from hemo (blood) that is in contact with the syncytiotrophoblasts of chorionic tissue
- #8 Simultaneously, lacunar spaces become confluent with one another and by 3rd and 4th week, form a multilocular receptacle lined by syncytium and filled with maternal blood. This space becomes the future intervillous space. As the growth of the embryo proceeds, decidua capsularis becomes thinner beginning at 6th week and both the villi and the lacunar spaces in the abembryonic area get obliterated, converting the chorion into chorion laeve. This is, however, compensated by (a) exuberant growth and proliferation of the decidua basalis and (b) enormous and exuberant division and sub-division of the chorionic villi in the embryonic pole (chorion frondosum). These two, i.e. chorion frondosum and the decidua basalis form the discrete placenta. It begins at 6th week and is completed by 12th week (Fig. 3.1). Until the end of the 16th week, the placenta grows both in thickness and circumference due to growth of the chorionic villi with accompanying expansion of the intervillous space. Subsequently, there is little increase in thickness but it increases circumferentially till term. The human hemochorial placenta derived its name from hemo (blood) that is in contact with the syncytiotrophoblasts of chorionic tissue (Fig. 3.4).
- #11 CONVEX TO POLYGINAL : Lobes or cotyledons 15-20 limited by fissures Each fissure is occupied by the decidual septum which is derived from the basal plate Numerous small grayish spots are visibA thin greyish, somewhat shaggy layer which is the remnant of the decidua basalis (compact and spongy layer) and has come away with the placenta, may be visible.le: du to calcium deposition: no clinical significance
- #14 2 plates chorionic and basal plate Chorionic plate lies internally, lined by amniotic memnrane. Umbilical corf attached to this plate Basal Plate: lies to the maternal aspect Betn 2 plates: intervilious space The basal plate are perforated by spoiral arteries thru which maternal bloof flows into intervillious space
- #15 The basal plate is perforated by the spiral branches of the uterine vessels through which the maternal blood flows into the intervillous space. At places, placental or decidual septa project from the basal plate into the intervillous space but fail to reach the chorionic plate. The septum consists of decidual elements covered by trophoblastic cells. The areas between the septa are known as cotyledons (lobes), which are observed from the maternal surface, numbering 15–20.
- #16 It is bounded on the inner side by the chorionic plate and the outer side by the basal plate, limited on the periphery by the fusion of the two plates. It is lined internally on all sides by the syncytiotrophoblast and is filled with slow flowing maternal blood. Numerous branching villi which arise from the stem villi project into the space and constitute chief content of the intervillous space
- #17 These arise from the chorionic plate and extends to the basal plate. With the progressive development — primary, secondary and tertiary villi are formed (Fig. 3.6). Functional unit of the placenta is called a fetal cotyledon or placentome, which is derived from a major primary stem villus. These major stem villi pass down through the intervillous space to anchor onto the basal plate (see Fig. 3.5). Functional subunit is called a lobule which is derived from a tertiary stem villi. About 60 stem villi persist in human placenta. Thus, each cotyledon (totalling 15–29) contains 3–4 major stem villi. The villi are the functional unit of the placenta. The total villi surface, for exchange, approximately varies between 10–14 square meters. The fetal capillary system within the villi is almost 50 km long. Thus, while some of the villi are anchoring the placenta to the decidua, the majority are free within the intervillous space and are called nutritive villi. Blood vessels within the branching villi do not anastomose with the neighboring one.
- #18 In placenta at term, syncytiotrophoblast becomes relatively thin at places overlying the fetal capillaries and thicker at other areas containing extensive endoplasmic reticulum. The former is probably the site for transfer and the latter, the site for synthesis. The cytotrophoblast is relatively sparse. Basement membrane becomes thicker. Stroma contains dilated vessels along with all the constituents and few Hofbauer cells (Fig. 3.11). Hofbauer cells are round cells (see Fig. 3.11) that are capable of phagocytosis and can trap maternal antibodies crossing through the placenta (immune suppressive). These cells can express class II MHC molecules
- #19 A mature placenta has a volume of about 500 mL of blood; 350 mL being occupied in the villi system and 150 mL lying in the intervillous space. the blood in the intervillous space is completely replaced about 3–4 times per minute. The villi depend on the maternal blood for their nutrition Areterial circulation: about 120-200 spiral arteries open to intervillous space by piercing basal plate randomly at numerous site. Normaly there is trophoblastic invasion at week 12 where the musculoelastic epith is replaced by fibrinoid material upto intradecidual potrion. There is secondary invasion between 12 and 16 weeks extending upto myometrium. The spiral artery is converted to large bore uteroplacental artery. Net effect funneling of artery which decrease pressure and increase flow.ok;l,
- #21 It is a partition between fetal and maternal circulation. However, this barrier is not a perfect barrier as fetal blood cells are found in maternal circulation so also the maternal blood cells are found in fetal circulation. The above two are separated by tissues called placental membrane or barrier, consisting of the following. Near term, there is attenuation of the syncytial layer. Sparse cytotrophoblast and distended fetal capillaries almost fill the villus. The specialized zones of the villi where the syncytiotrophoblast is thin and anuclear is known as Vasculosyncytial membrane (Fig. 3.11). These thin zones (0.002 mm) of terminal villi alpha zones are for gas exchange. The thick ‘beta zones’ of the terminal villi with the layers remaining thick in patches are for hormone synthesis. An increase in thickness of the villous membrane is seen in cases with IUGR and cigarette smokers.
- #22 As the placenta has got a limited life span, it is likely to undergo degenerative changes as a mark of senescence. The ageing process varies in degree and should be differentiated from the morbid process likely to affect the organ in some pathological states. The ageing process involves both the fetal and maternal components. Decreasing thickness of syncithium Partial disappearance of trophoblastic cells Decrease in stromal tissue including hofbaeur cells Obliteration of some vessels and marked dilatation of capillaries Thickening of basement layer of fetal endothelium and cytotrophoblast Deposition of fibrin on the surface of villi
- #26 Spatial arrangement of atoms concern how different atomic particles and molecules are situated about in the space around the organic compound, namely its carbon chain.
- #27 Bulk flow: bulk flow of water along with dissolved solutes occurs through differences in hydrostatic and osmotic pressure 1) Simple diffusion. (2) Facilitated diffusion (transporter mediated) using transporter proteins in syncytiotrophoblast. Glucose amino acids (3) Active transfer (against concentration gradient, energy ATPase, mediated). (4) Endocytosis: Invagination of the cell membrane to form an intracellular vesicle which contains the extracellular molecules. (5) Exocytosis: Release of the molecule within vesicle to the extracellular space. Immunoglobulin IgG is taken up by endocytosis from maternal circulation and is transferred to the fetus via exocytosis. (6) Leakage (break in the placental membranes).
- #30 Glucose which is the principal source of energy is transferred to the fetus by facilitated diffusion. There are transporter proteins (GLUT I) for facilitated diffusion. Glucose transfer from mother to fetus is not linear. Transfer rates decrease as maternal glucose concentration increases. Fetal glucose level is lower than that of the mother indicating rapid rate of fetal utilization of glucose. Lipids for fetal growth and development are transferred across the fetal membrane or synthesized in the fetus. Triglycerides and fatty acids are directly transported from the mother to the fetus in early pregnancy but probably are synthesized in the fetus later in pregnancy. Essential fatty acids are transferred more than the non-essential fatty acids. Cholesterol is capable of direct transfer. Thus, fetal fat has got a dual origin. • Amino acids are transferred by active transport (energy requiring transport) through enzymatic mechanism (ATPase). Amino acid concentration is higher in the fetal blood than in the maternal blood. Some proteins (IgG), cross by the process of endocytosis. Fetal proteins are synthesized from the transferred amino acids and the level is lower than in mother. • Water and electrolytes such as sodium, potassium and chloride cross through the fetal membrane by simple diffusion, whereas calcium, phosphorus and iron cross by active transport (active transporter proteins) against a concentration gradient, since their levels are higher in fetal than in maternal blood. Water soluble vitamins are transferred by active transport but the fat soluble vitamins are transferred slowly so that the latter remains at a low level in fetal blood. • Hormones — insulin, steroids from the adrenals, thyroid, chorionic gonadotrophin or placental lactogen cross the placenta at a very slow rate, so that their concentration in fetal plasma are appreciably lower than in maternal plasma. Neither parathormone nor calcitonin crosses the
- #31 Pinocytosis (“pino” means “to drink”) is a process by which the cell takes in the fluids along with dissolved small molecules. In this process, the cell membrane folds and creates small pockets and captures the cellular fluid and dissolved substances.
- #59 Non protein nitrogen
- #61 The umbilical cord is developed from the connective stalk or body stalk, which is a band of mesoblastic tissue stretching between the embryonic disc and the chorion. Initially, it is attached to the caudal end of the embryonic disc but as a result of cephalocaudal folding of the embryo and simultaneous enlargement of the amniotic cavity, the amnioectodermal junction converges on the ventral aspect of the fetus. As the amniotic cavity enlarges out of proportion to the embryo and becomes distended with fluid, the embryo is carried more and more into the amniotic cavity with simultaneous elongation of the connective stalk, the future umbilical cord.
- #62 Covering epithelium: It is lined by a single layer of amniotic epithelium but shows stratification like that of fetal epidermis at term. 2. Wharton’s jelly: It consists of elongated cells in a gelatinous f l u i d formed by mucoid degeneration of the extraembryonic mesodermal cells. It is rich in mucopolysaccharides and has got protective function to the umbilical vessels. Blood vessels: Initially, there are four vessels — two arteries and two veins. The arteries are derived from the internal iliac arteries of the fetus and carry the venous blood from the fetus to the placenta. Of the two umbilical veins, the right one disappears by the 4th month, leaving behind one vein which carries oxygenated blood from the placenta to the fetus. Presence of a single umbilical artery is often associated with fetal congenital abnormalities (see p. 218). Remnant of the umbilical vesicle (yolk sac) and its vitelline duct: Remnant of the yolk sac may be found as a small yellow body near the attachment of the cord to the placenta or on rare occasion, the proximal part of the duct persists as Meckel’s diverticulum. Allantois: A blind tubular structure may be occasionally present near the fetal end which is continuous inside the fetus with its urachus and bladder. Obliterated extraembryonic coelom: In the early period, intraembryonic coelom is continuous with extraembryonic coelom along with herniation of coils of intestine (midgut). The condition may persist as congenital umbilical hernia or exomphalos.
- #66 PLACENTA EXTRACT (HUMAN) belongs to the class of dermatological preparations used to treat chronic non-healing wounds or delayed wound healing (in case of diabetes). Besides this, it also treats wounds associated with burns, chronic ulcers, or other skin defects.