RDA Module

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RDA Module

Iatrogenic disease

1. Eg drug induce parkinsonism

2. A disease cause by the process of diagnosis or treatment

3. Affect 10% hospitalized geriatric patient 4. 2 main adverse drugs reaction

o Type A- are attributable to accentuation of a drugs known for pharmacological actions,

related to dose, predictable, relatively common

o Type B-are idiosyncratic, unrelated to dose, f requently unpredictable and of unknown

mechanism, governed by host f actors such as genetics or allergy, less common but

of ten more serious.

5. Factors for high incidence of ADR

o Inadequate clinical assessment and multiple disorder

o Excessive prescription and inadequate reviewed of medication

o Altered pharmacokinetics in old people absorption in the gut, drug metabolism by

liver, clearance in by the kidneyo Altered pharmacodynamics. Ie greater anticoagulant effect,

o Impaired compliance. Ie- live alone, poor instruction by doctor

Reproductive tract

1. Male reproductive tract

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Organ Cell/tissue Structure, funtions

Testis Spermatogonia

Spermatocyte

Spermatid

Spermatozoa

Sertoli cellLeydig cell

Secrete inhibin, has receptor for FSH,sperm blood barrier Secrete testosterone, has receptor for LH

Epidydimis Principal cell Pseudostratified columnar epi, stereocilia

Basal cell Pseudostratified columnar epi

Vas deferens Pseudostratified columnar epi

Seminal ves Secrete carbohydrate such as f ructose

Prostate Stroma Smooth muscle and FCT

Glandular tissue Low cuboidal or columnar epi (citrate and PG)

penis Corpus spongiosum Containing urethra

Corpus cavernosum Helicine arteries in the centre and surrounding venous blood

sinuses

2. Female reproductive tract

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Sperm transport

1. ejaculation produces: (average 50 million per ejaculation)o 1.56ml of semen

o 15-200 million sperm / ml

o 4070% of these sperm are motile

o 5% of sperm are structurally or biochemically normal

2. Menstrual cycle

3. Sperm transport in vagina ~50mil sperm

o Normal vaginal pH ~ 4.2,

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o With lubrication (sexual arousal) and presence of semen the acidity decreases to pH ~

7.2.

o Sperm survives because of space and acidity.

4. Sperm transport in cervix. ~ 5 mil

o Mucus produce f rom cervical gland

o 2 type of cervical mucus. Type E-low viscosity (fertile phase). Type G (high viscosity)

5. Sperm transport in uterus ~1mil

o Sperm enter cervix by their own movement

o In uterus this movt. f acilitated by smooth muscle activity of uterus. Increase during

follicular phase due to oxytocin (coitally induced) and prostaglandin (f rom semen)

o Sperm initiate invasion of leukocyte

6. Coital f actors in sperm transport.

o Position

o Arousal

7. Fecundity (ability to reproduce)

o Reach almost 100% af ter 12cycles

o Factors- f req of intercourse (increase will increase), timing (max in 12,13,14 day of

cycle), age, contraceptive, sperm transport (retrograde ejaculation)

8. Infertility- inability of conceive af ter 1 year of trying for pregnancy.

o Sub-infertility

o Sterility (prevention tubal sperm)- vasectomy,

o Antisperm antibodieso Treatment- intrauterine insemination

Fertilization and implantation

1. Ovulation

o Prior to ovulation-LH surge

-select a large pre-ovulatory follicle

-induces oocyte to complete 1st

meiosis-oocyte + a polar body

2. Fertilization

o Sperm bind with corona radiata (wiki)

o Sperm penetrate zona pellucida

o Sperm-oocyte membranes fusion- complete 2nd meiosis and 2nd polar body

o Female and male pronuclei fusiony Prevent polyspermy

1) Reducing sperm number reaching oviduct

2) Af ter nuclei fusion- rapid protein conformation change to zona

pellucida and changes too oocyte membrane

3. Early development in oviduct

o 1 cell=zygote

o >1= embryo. No new mRNA on 4 cells embryo. Reliant on maternal transcript

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o Morula (4th

day)

o blastocyst(~6th

day. Inner cell mass/ embryoblast + outer trophoblast), hatching f rom

zona pellucida

o 6-7 days to reach uterus

4. Implantation (prep- progesterone + oestradiol for secretory endometrium and epithelial

receptivity). Complete at 14th

day

o Blastocyst attachment- require trophoblast

o Blastocyst invasion- through epithelium into stromal tissue. Some stroma cell become

decidual cells (cellular degeneration). This restrict the invasion of the trophoecoderm.

Decidual tissue not present in other organ. Ectopic pregnancy potential for serious

haemorrhage.

5. Consequence of implantation

o Formation of embryo bilaminar disc (epiblast and hypoblast)

o Formation of initial placenta

o Secretion of hCG- prevents lysis of corpus luteum therefore progesterone secretion

continues

o Formation of trilaminar layer by migration of epiblast forming endoderm layer start at

day 14

Formation of Ovulation

Maternal adaptation of pregnancy

1. Changes- anatomy, physiology, metabolic

2. Functions

o Support fetal homeostasis & growth

o Do not jeopardise maternal wellbeing

o Remodelling of maternal systems

o Deliver nutrients, oxygen & energy to the fetus

o Remove waste products

3. Physiology and anatomy changes

o Uterus- hypertrophy, hyperplasia on myometrium, hypertrophy on nerves,

vascularity, by 12 weeks shape almost spherical the rapid growth, with ascent of

uterus f rom uterus underwent dextrorotation

o Cervix- sof tening, vascularity, hypertrophy, hyperplasia, mucus plug,

o Vagina- acidic secretion, vascularity, epi thickness, hypertrophy of smooth muscle

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o Ovary- cessation of ovulation and formation new follicle, corpus luteum secrete P till

about 14-16 weeks, suppresses prostaglandin in deciduas, relaxin-sof ten joint by

remodeling CT

o Skin- hyperaemia and blood flow, (vasodilation) spider navi, linea nigra (melanin

deposition), striae gravidarum-collagen breakdown,

o Breast- tenderness, tingling, hypertrophy, nodularity, pigmentation, striae, colostrum

secretion,

o MSK- mobility, back pain due joint mobility, progressive lordosis

o CVS- circulating blood volume, peripheral vascular compliance and resistance,

myocardial contractility, heart rate, and the neurohormonal system by.

-heart hypertrophy & push upwards and lateral-apex at 4th intercostals space, venous

return (NO,PG) right atrium hypertrophy ANPnatriuresis blood volume,

overall increase blood vol 40% (estrogen renin, water retention +

prolactin,PG,growth hormone), CO, HR,SV, diff between systolic & diastolic, no

change in MAP, supine hypotension (compression on IVC), regional blood flow to all

region,

o RESP- O2 consumption, elevation of resting diaphragm, functional residual vol,

dyspnea, tidal volumeo Renal- collecting system dilation, kidney increase in size, compressed ureter-risk of UTI,

RBF, GFR, ECF, renin

o GI- bowel displacement, Ca absorption, heartburn, progesterone induce craving,

o Gallbladder- progesterone inhibit gallbladder contraction, increase bile, gallstone

formation, intrahepatic cholestasis

o Metabolic- diabetogenic state, increase insulin resistance, hyperinsulinaemia,

o Blood coagulation- hypercoagulable state

o Pituitary- size, prolactin

o Adrenal- ACTH and cortisol

o Acid-base balance- Metabolic state of pregnancy chronic respiratory alkalosis with a

compensated metabolic acidosis4. Peripartum- catecholamine secretion, HR, uterine contraction, central blood volume

5. Postpartum- haemodynamic parameters return to baseline within 6 months

Placenta

1. Placenta has 2 components

o Embryo-trophoblast

o Maternal- decidua

2. Process

o Trophoblast invade the uterine endothelium completely enclosed in uterine wall (7day-

10day)

o The syncytiotrophobalst invades the uterine wall and erodes the lining capillaries

forming trophoblastic lacunae

o At the same time ICM forming bilaminar embryo. Maternal blood enters the lacunae so

that the naternal blood in contact with the trophoblast

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o Primary villi (2-3weeks)- finger-like protrusions of cytotrophoblast covered by

syncytiotrophoblast into lacunae.

o Secondary villi (week 3)- extraembryonic mesoderm invade the centre of the villi then

differentiate into bleed vessels

o Tertiary villi (week 3)-when blood vessels present in the villi. At the same time the

embryonic heart and circulation is developing link up with those in the villi. No direct

communication between maternal and embryo/fetal circulation. As fetus grows, the

tertiary villi change in structure so that the thickness of the barrier decrease.

o As embryo grow, it invade uterine cavity. The part of trophoblast that remain in contact

with uterine wall is called chorion f rondosum/placenta. While the remaining thin and

smooth is called chorion lavae. It fuse with amnion to form the extraembryonic

membrane.

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3. Functions

o Hormone productions- hCG, human placenta lactogen, progesterone, oestrogen,

o Exchange- gas, nutrients, electrolyte

o Protection- against maternal antibodies, drugs,

4. Extraembryonic membrane

o Chorion-

o Amnion-

5. Amniotic fluid

o Origin-

amnion memb

rane, m

aterna

l bloodo Role- allow movement, shock absorber, prevent desiccation, prevent adhesion

between fetus and surrounding membrane.

6. Twins

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Organogenesis- respiratory system

1. Respiratory tissue

Day/week Phase Description

23day Body folding Trilaminar embryo folds into ..

26/27 day Embryonic Respiratory diverticulum bud off f rom primitive foregut.

Formation of lung bud- bronchopulmonary segment- grows in

surrounding mesoderm

Week5-16 Pseudoglandular Formation terminal bronchioles

Week16-26 Canalicular Respiratory bronchioles

Vascularisation by trapping blood vessels

Week 24-36 Saccular Terminal sac

Week 36-38 Alveolar Alveoli maturation. Develop into type I and II respiratory epithelium

2. Formation of thoracic cavities

o Formation of diaphragm

1) Start at the level of neck therefore nerve innervations f rom C3-5)

2) 3 separates components

Pleuroperitoneal folds muscular diaphragm

Septum transversum between liver and lungs central tendon + fibrous

pericardium

Esophagus mesentary

o Division between thoracic cavities and pericardium

1) From pleuropericardial fold enclosing the heart

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Organogenesis- heart and circulation

1. Can divide process into 5 components:

o Formation and folding of tube that will become the heart.

Cluster of angiogenic cells form a single heart tube

Arterial endsventricleatriumvenous endsThen the tube fold upwards

o Separation into atria & ventricles

Formation atrioventricular canals

o Division of common atria to form R & L atria.

Septum primum + ostium primumseptum secundum +ostium secundam. No more

ostium primumforamen ovale + valve

o Division of common ven

tricle in

to R & L Ven

tricles

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o Formation of aorta and pulmonary trunk

2. Fetal circulation

Organogenesis- GI

1. Start with single tube suspended on mesentery

2. Foregut

o The lower foregut begins at the level of the lung buds with the

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esophagus, followed by the stomach and the superior part of the

duodenum.

o It extends as f ar as the liver bud and the pancreas, the bile passages also

arise f rom it.

o Between stage 14 (ca. 33 days, 14 ) and 20 (ca. 49 days, 20 ) a

massive lengthening of the whole intestines in a cranio-caudal growth

gradient takes place: in the beginning it is mainly the esophagus and

stomach that lengthen. Thus a shif t of these structures relative to the

vertebral column occurs.

o descent of the stomach. This lengthening not only leads to a relative

relocation with respect to the spine but it also coupled to the so-called

"stomach rotation".

3. Midgut

o Week6- physiological herniation into umbilical cord

the midgut begins to extend into the umbilical coelom and forms the

umbilical loop

o Week 10- rotation and return to abdominal cavity

Only when the umbilical loop lengthens and grows into the umbilicalcoelom does it experience a rotation of 90 degrees in a clockwise

direction. The umbilical loop now has a horizontal position. As

development proceeds the intestinal loop turns further around its own

axis. In stage 18 (ca. 44 days, 18 ) the extension of the intestinal

loop into the umbilical coelom has reached its maximum. This

physiologic navel hernia remains in existence up to the 9th week of

pregnancy. the loops of the small intestine return into the abdominal

cavity and come to lie in the lef t half surrounded by the horizontal and

descending part of the colon that never lef t the abdominal cavity. The

rotation now amounts to more than 180 degrees (total 270 degree) and

the colon is also shif ted more and more into the abdominal space.o Abnormalities includes malrotation, omphalocoele, meckels

diverticulum

4. Hindgut

o The hindgut extends f rom the left third of the transverse colon to the

cloaca (rectum). In contrast to the midgut, no intestinal rotation occurs

here but rather this part gets pushed to the lef t side by the midgut

returning f rom the umbilical coelom

o In addition, at its end, it is connected to the allantois and to the

mesonephric duct

o the urorectal septum, arises in the angle between the allantois and the

hindgut. Through this mechanism, the cloaca is subdivided into the

urogenital sinus (ventrally) and the anorectal canal (dorsally)

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