General Pathology (genetics & developmental diseases / prematurity, fluid & hemodynamic disorders) Flashcards
lecture 8 (prematurity, fluid and hemodynamics disorders)
..
prematurity
..
how long normal pregnancy last
Normal pregnancy lasts 40 weeks (9.2 months)
what is avergae fetus weight
Fetus attains viability and average weight of 3500g (7 lbs 12 oz)
7.7 pounds
3500g
what is prematurity
children born before 37th week and less than 2500 g
(5.5 pounds)
“Low birthweight is when a baby is born weighing less than 5 pounds, 8 ounces”
“Some babies with low birthweight are healthy, even though they’re small. But having a low weight at birth can cause serious health problems for some babies.”
immaturity
(infant immaturity)
less than 1500g; cannot survive outside neonatal intensive care units
1500g
(3.3 pounds)
neonatal intensive care unit
“Newborn babies who need intensive medical care are often put in a special area of the hospital called the neonatal intensive care unit (NICU)”
neonatal meaning
Neonatal refers to the first 28 days of life.
spontaneous aboriton / miscarriage
Approximately 5-10% of pregnancies terminate prematurely
why “ ??
Maternal factors
Fetal factors
Placental factors
when does maturation of fetal lungs occur (which portion of pregnancy?)
last 3 months of pregnancy
what happens during this time (that fetal lungs mature) ?
lungs expand and principle components of alveoli are formed
what do avleolar cells secrete?
Alveolar cells begin secreting surfactant
Keeps alveoli open
surfactant define
a substance which tends to reduce the surface tension of a liquid in which it is dissolved.
surfactant in lungs
Surfactant is a mixture of fat and proteins made in the lungs. Surfactant coats the alveoli (the air sacs in the lungs where oxygen enters the body).
This prevents the alveoli from sticking together when your baby exhales.
“Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing.”
atelectasis
partial or complete collapse of the lung.
ateles = imperfect
ektasis = extension
Neonatal Respiratory Distress Syndrome (NRDS)
If fetus born prematurely, functionally immature lungs cannot sustain normal respiration
—> (NO SURFACTANT (?) not enough (?))
Alveoli collapse
Oxygen cannot diffuse into circulation
Cells damaged and die
Neonatal Respiratory Distress Syndrome (NRDS)
AND NECROSIS
Necrotic cells and proteins coagulate and form HYALINE MEMBRANES
Gas exchange impeded
Infant can die of anoxia within 48 hours
Anoxia most prominently affects brain
HYALINE MEMBRANES
When there is not enough surfactant, the tiny alveoli collapse with each breath.
As the alveoli collapse, damaged cells collect in the airways, which makes it even harder to breath.
These cells are called hyaline membranes.
hyaline
hualos = glass
hyaline
—> “having a glassy, translucent appearance.”
Hyaline Membrane Disease (HMD) ?
also called respiratory distress syndrome (RDS), is a condition that causes babies to need extra oxygen and help breathing.
one of the most common problems seen in premature babies ?
HMD is one of the most common problems seen in premature babies.
hyaline membrane disease (neonatal respiratory distress syndrome)
PATHOGENESIS
Prematurity (<36 weeks)
Multiple pregnancy/birth (more than one fetus)
Maternal diabetes
Cesarean Section
Amniotic fluid aspiration
maternal diabetes and NRDS (HMD)
Fetal hyperglycemia and hyperinsulinism secondary to maternal diabetes disrupt normal surfactant synthesis and function, which leads to surfactant inadequacy and clinical RDS in neonates.
C section – why risk factor for NRDS (?)
Cesarean section is a risk factor for RDS because the fetus absorbs about one-third of the fetal lung fluid during vaginal delivery,
whereas proper absorption of fetal lung fluid is not achieved in infants delivered through a cesarean section.
Amniotic fluid aspiration and NRDS
What Causes Meconium Aspiration Syndrome?
Meconium aspiration happens when a baby is stressed and gasps while still in the womb,
or soon after delivery when taking those first breaths of air.
When gasping, a baby may inhale amniotic fluid and any meconium in it.
meconium
the dark green substance forming the first feces of a newborn infant.
While babies most often hold out on pooping until they’re born, they are certainly active urinators in the womb.
placenta helps remove some of this waste naturally
Some pee will remain in the amniotic fluid, but it’s not considered dangerous for your baby like meconium can be.
mechanism / pathogenesis (NRDS)
immature/damaged type 2 pneumocytes
—> low level surfactant
—> lung collapse
—> hypoxia
–> alveolar lining damage / pulmonary vasoconstriction
–> endothelial damage
—> Fibrin Hyaline membranes
–> HYPOXIA (vicious cycle)
Sudden Infant Death Syndrome (SIDS)
Sudden unexpected death in infants between the ages of 2 – 9 months
SIDS aka
Also known as “crib death”
about
Seemingly healthy infants
Occurs during sleep
No obvious cause of death on autopsy
Most common cause of deaths in infants beyond neonatal period
SIDS
SIDS rate
Occurs in 1/500 births (according to Damjanov – may be outdated –> maybe closer to 1/1500 - 1/2000
most common in which groups?
Most common in young mothers, women of low socioeconomic status and education, smokers, substance abusers
other risk factors?
Genetic component
Premature infants at risk
Pathogenesis unknown
“Back to sleep” campaign has drastically reduced incidence
Back to sleep campaign
The Safe to Sleep campaign, formerly known as the Back to Sleep campaign
initiative backed by the US National Institute of Child Health and Human Development (NICHD)
encourage parents to have their infants sleep on their backs (supine position) to reduce the risk
Since “Safe to Sleep” was launched in 1994, the incidence of SIDS has declined by more than 50%.
leading causes of infant deaths in US, 2009
Birth defects = 5358
Low Birth Weight and Prematurity = 4528
SIDS = 2231
Maternal Complications = 1614
Accidents = 1172
Fluid and Hemodynamic disorders
..
about water in body
Water – 60% of total body weight
2/3 – intracellular
1/3 – intercellular spaces; blood (80/20 plasma)
“Blood fluids must be in counterbalance with other fluid compartments”
overhydration vs dehydration
When boundaries of normal variation exceeded – overhydration, dehydration occurs
factors related to fluid dynamics
Factors to consider:
Redistribution of body fluids
Loss of fluids
Retention of fluids
Disruption of circulation
Edema define
Definition: excess fluid in tissues or body cavities
local or general?
Localized or generalized
general edema is called
Anasarca – generalized edema
Anasarca etymology
From Ancient Greek ἀνα- (ana-, “up to, thoroughly”) + σάρξ (sárx, “flesh, body”), short for ὕδρωψ ἀνὰ σάρκα (húdrōps anà sárka, literally “dropsy throughout the flesh”). Compare hyposarca.
dropsy define
An old term for the swelling of soft tissues due to the accumulation of excess water.
Edema in specific regions/organs
Cerebral edema - brain
Pulmonary edema - lungs
Macular edema - eyes
Ascites - edema within the peritoneal cavity
Pleural effusions - edema in the pleural cavity
(note joint effusions)
ascites
the accumulation of fluid in the peritoneal cavity, causing abdominal swelling.
ascites:
askos = wineskin
types of edema ??
Exudate vs Transudate
Exudate (edema)
High in protein and cells
Typical of inflammation
Transudate (edema)
High in protein (but less than exudate)
Low in cells
Transudate may accumulate due to the following:
1) increased hydrostatic pressure
2) reduced oncotic pressure
3) lymphatic obstruction
—> (FLUID FROM BV to TISSUE to LYMPH – but if lymph blocked, then fluid stays in tissue)
4) sodium retention
osmotic vs hydrostatic pressure
Whereas hydrostatic pressure forces fluid out of the capillary, osmotic pressure draws fluid back in.
Osmotic pressure is determined by osmotic concentration gradients, that is,
the difference in the solute-to-water concentrations in the blood and tissue fluid.
mroe about fluid in BV vs IS space
Fluid in circulating blood is separated from interstitial fluid by blood vessel wall (semipermeable membrane)
Movement across this barrier is determined by several factors (HS pressure, oncotic pressure, lymph blockage, sodium/ion retention
Hydrostatic pressure @ arterial end of capillary
vs
@ venous side of capillary
At the arterial end of a capillary, hydrostatic pressure exceeds the hydrostatic pressure on the venous side of the capillary promoting the passage of fluids into the interstitial fluid
I.e.
more fluid exiting capillaries (transudate?) @ arterial end of capillary
—> (greater pressure)
About Oncotic pressure
Aka colloid osmotic pressure
The pressure due to the presence of colloids in the blood
Colloids – any large molecule such as starch or protein
Colloids act like a sponge
so then why edema?
Edema occurs as a result of imbalance between forces that keep the fluid in the vessels and those that promote its exit into the tissues.
other classification for edema
Inflammatory edema
Hydrostatic edema
Oncotic edema
Obstructive edema
Hypervolemic edema
Inflammatory edema
Inflammatory edema: fluid leaks through the vessel wall which has been made more permeable
Hydrostatic edema
intravascular pressure promotes the transmembranous passage of fluids
oncotic edema
Oncotic edema: decreased plasma proteins or decrease in colloid osmotic pressure
Particularly proteins
Specifically albumin
obstructive edema
Obstructive edema: very rare; can be caused by parasites or worms (Africa) or tumour cells
(lymphatics obstruction)
why lymphatic edema?
parasites/worms
tumours cells
hypervolemic edema
kidney dysfunction leading to the retention of sodium and water
edema factors
Edema is usually multifactorial
Combination of many factors
Clinically important finding that may indicated dysfunction of major organs including kidneys and heart
note heart and edema
Congestive heart failure = edema in lungs or extremities
clinical types of edema (via edema @ specific location/organ)
Cerebral edema
Pulmonary edema
Pitting edema of lower extremities
Periorbital (facial) edema
Hydrothorax
Hydroperitoneum (ascites)
Anasarca
“pitting” edema
Pitting edema occurs when excess fluid builds up in the body, causing swelling;
when pressure is applied to the swollen area, a “pit”, or indentation, will remain.
Although it can affect any part of the body, pitting edema usually occurs in legs, feet, and ankles.
Hyperemia
“Too much blood”
Increase of blood flow to different tissues in the body due to the presence of metabolites and/or a change in general conditions
3 types of hyperemia
- Active
- Reactive
- Passive
active hyperemia
Aka functional hyperemia
The increased blood flow that occurs when tissue is active and requires more metabolites
Typically occurs during blushing, exercise or acute inflammation
when does active hyperemia typically occur?
blushing, exercise or acute inflammation
reactive hyperemia
Occurs in response to a profound increase in blood flow to an organ after being occluded
There will be a shortage of oxygen and a build-up of metabolic waste
E.g.
ischemic compressions (technique)
Passive hyperemia
Aka congestion
Caused by increased venous backpressure
Typically a consequence of heart failure
Often occurs in chronic form
Can lead to cyanosis (bluish tissues)
example of reactive hyperemia
ischemic compressions
typical of passive hyperemia
E.g. CHF
Passive Hyperemia is when parts of the body are clogged, or the blood is clotted and can’t flow. These conditions happen within your blood and organs, and may include: Heart failure
cyanosis typical of
& define
typical of passive hyperemia
define:
a bluish discoloration of the skin resulting from poor circulation or inadequate oxygenation of the blood.
Hemorrhage define
Loss of blood from the circulatory system
Can occur internally - blood leaks from blood vessels inside the body
Can occur externally, either through a natural opening such as the mouth, or through a break in the skin
internal vs external hemorrhage
”
how much blood loss can typcially be endured?
Loss of 10-15% of total blood volume can be endured without clinical consequences
(blood donation typically takes 8-10% of the donor’s blood volume)
when does hemorrhage become life-threatening
Hemorrhage becomes dangerous, or fatal, when it causes hypovolemia (low blood volume) or hypotension (low blood pressure)
how much blood loss fatal
Losing (40-)50% of the blood in your body may be fatal, but minor blood loss doesn’t pose any lasting risk to your health.
You can generally lose about 14% of the blood in your body without any major side effects, though you may feel dizzy or lightheaded.
If you lose more than 40 percent of your blood, you will die. This is about 2,000 mL, or 0.53 gallons of blood in the average adult. It’s important to get to a hospital to start receiving blood transfusions to prevent this.
hypovolemia define
a decreased volume of circulating blood in the body.
If you have hypovolemia, you lose more than 15% of the total volume of fluid within your circulatory system
Immediate treatment for hypovolemia is necessary to prevent life-threatening complications like organ damage, shock or death.
hypotension
Hypotension is a decrease in systemic blood pressure below accepted low values. While there is not an accepted standard hypotensive value, pressures less than 90/60 are recognized as hypotensive.
Severe hypotension (shock) can be caused by sudden loss of blood (shock), severe infection, heart attack, or severe allergic reaction (anaphylaxis).
“If your blood pressure drops too low, your body’s vital organs may not get enough oxygen and nutrients, which can lead to a medical emergency”
classification of hemorrage via duration and source/location
DURATION:
Acute
Chronic
Recurrent
SOURCE:
Cardiac
Aortic
Arterial
Capillary
Venous
Cardiac hemorrhage
May result from gunshot or stabbing
May result from softening of heart wall through myocardial infarct
Often fatal
Aortic hemorrhage
Often caused by trauma (e.g. car accident)
Can occur due to aortic wall weakening and dilation (aortic aneurysm)
Arterial hemorrhage
Caused by penetrating wounds from gun or knife
Can also occur due to fracture
danger of arterial blood loss (arterial hemorrhage)
NOTE:
Arterial blood is bright red and under pressure (pulsating); arterial blood loss often fatal
capillary hemorrhage
Marked by pinpoint droplets of blood appearing on mucosa or skin or tissues
Can be related to trauma, increased venous pressure, weakening of capillary walls, Vitamin C deficiency
Venous hemorrhage
Usually traumatic
Dark red or bluish
Not pulsating
other terms/definitions
Hemothorax - blood in thoracic cavity
Hemoperitoneum - blood in peritoneal cavity
Hemopericardium - blood in the pericardial cavity
Hematomas - blood filled swellings
—> “a solid swelling of clotted blood within the tissues.”
Petechiae
small hemorrhages of skin and mucosa
“dots”
petecchia = freckle/dot
Purpura
medium hemorrhages of skin and mucosa
4-10 mm in diameter
—> smaller than 4mm = petechiae
—> larger than 10mm = ecchymosis
purpura = PURPLE
ecchymoses
large blotchy bruises
hemoptysis
blood in respiratory tract, coughing up blood,
can be due to lung cancer, TB, etc.
hemoptysis etymology
hemo = blood
ptysis = Ptysis is Greek for Latin sputa {“spit, spittle”} or sputamina meaning the same.
Hematemesis
vomiting blood;
can be due to esophageal cancer
hemato
emesis = vomiting
emein = to vomit
Melena
black, discoloured blood in stool;
can be due to stomach cancer
Melena – WHERE does the bleeding occur?
“Melena” is the medical term for the black, tarry stool that
comes from bleeding in your upper gastrointestinal (GI) tract.
Black stool is a sign of OLDER blood in your stool.
melena etymlogy
melas = black
Hematochezia
anorectal bleeding;
can be due to hemorrhoids
hematochezia – where does blood come from
lower GI bleeds
hematochezia etymology
The term is from Greek αἷμα (“blood”) and χέζειν (“to defaecate”).
Hematochezia is commonly associated with lower gastrointestinal bleeding
hemorrhoids define
Hemorrhoids (HEM-uh-roids), also called piles, are swollen veins in the anus and lower rectum.
Hemorrhoids are similar to varicose veins.
Hemorrhoids can develop inside the rectum, called internal hemorrhoids.
They also can develop under the skin around the anus, called external hemorrhoids.
hemorrhoid etymology
from haima ‘blood’ + an element related to rhein ‘to flow’.
metrorrhagia
Metrorrhagia – uterovaginal bleeding; can be due to cervical or uterine cancer
metro:
“a combining form meaning ‘uterus,’”
menorrhagia
heavy menstrual bleeding; can be due to endometriosis
endometriosis define
a condition resulting from the appearance of endometrial tissue outside the uterus and causing pelvic pain.
endometrial tissue / endometrium
The layer of tissue that lines the uterus
hematuria
Hematuria – blood in urine; can be due to kidney infection
“clinical correlation”
Depend on:
Amount of blood loss
(Duration)
Site of hemorrhage
Other factors
Massive Acute hemorrhage
Potential life-endangering event
Up to 500mL loss – no consequences
1000-1500mL – shock
More than 1500 - lethal
(40% = 2000mL)
Chronic hemorrhage
E.g.
Bleeding gastric ulcer
Heavy menstruations
Result in anemia
other clinical correlations
Extravasated blood can damage tissues
Large hematomas are space occupying lesions
Can compress normal structures (MASS EFFECT?)
Can cause pain
mass effect hematoma E.g.
The hematoma can exert a mass effect on the brain, increasing intracranial pressure and potentially causing midline shift or deadly brain herniation.
Lecture 7 – genetic and developmental diseases
..
about normal embryonic development
..
zygote
Fertilization between egg and sperm yields zygote
zygote define
a diploid cell resulting from the fusion of two haploid gametes; a fertilized ovum.
what does zygote cell divide into
Zygote cells divide to form morula
morula define
A morula (from Latin “morus” meaning mulberry) is an embryo at an early stage of embryonic development, consisting of approximately 8–32 cells (called blastomeres).
blastomere
In biology, a blastomere is a type of cell produced by cell division (cleavage) of the zygote after fertilization; blastomeres are an essential part of blastula formation, and blastocyst formation in mammals.
blastula deifne
an animal embryo at the early stage of development when it is a hollow ball of cells.
morula vs blastula (vs gastrula vs blastocyst)
When a solid, compact cluster of 16 cells is present, which occurs at about 3 days post-fertilization in human beings, the zygote becomes a morula.
After several more cellular divisions, the morula becomes a hollow ball called a blastula.
(The gastrula develops from the hollow, single-layered ball of cells called a blastula)
In mammals, the blastula structurally reorganizes into a blastocyst.
morula (—> blastula —> gastrula) —> blastocyst
Morula transforms into blastocyst
blastocyst invading uterine wall —> development of three GERM LAYERS
The second and third weeks of embryological development are crucial, involving the implantation of the blastocyst into the uterine wall
the establishment of three distinct germ layers - the mesoderm, endoderm and ectoderm - through gastrulation
gastrulation define
the process by which a gastrula forms from a blastula.
gastrula
The gastrula develops from the hollow, single-layered ball of cells called a blastula which itself is the product of the repeated cell division
gastrula vs blastocyst
Blastocyst is an early embryonic stage in mammals (otherwise it is a blastula), which is followed by development of gastrula.
blastocyst / germ layers
Inner cell mass gives rise to primordial germ layers: ectoderm, endoderm, mesoderm
(after invading uterine wall)
fetal organs
Fetal organs and tissues including
muscle,
bone,
nervous tissue,
develop from primary germ layers
critical stage of ORGANOGENESIS
Characterized by extensive cell division, migration and cell-to-cell interaction
Developing organs very sensitive to external influences
what are exernal influences that affect developing organs?
what is TERATOLOGY
most importantly, chemical, physical and viral agents
Disturbance in development is called teratology
teratology define
the scientific study of congenital abnormalities and abnormal formations.
teratogen
Teratogen – causes fetal abnormalities
“an agent or factor which causes malformation of an embryo.”
fetal abnormalities etiology percentage
75% of cases idiopathic, 20% genetic diseases
(2% chromosomal abnormalities,
2% infections,
1% chemicals)
chromosomal abnormalities vs genetic disorders
Inherited disorders are caused by gene mutations. These include disorders such as cystic fibrosis, sickle cell disease, and Tay-Sachs disease.
Chromosomal abnormalities occur when there are missing or extra chromosomes or pieces of chromosomes.
(Those that produce changes in a single gene are known as gene mutations. Those that produce changes in whole chromosomes are known as chromosomal mutations.)
exogenous teratogens (physical)
X-rays
Radiation – gamma, beta, alpha rays
exogenous teratogens (chemical)
Many man made and many exists in nature (e.g. Thalidomide)
Most important - alcohol
thalidomide tragedy
Thalidomide was a widely used drug in the late 1950s and early 1960s for the treatment of nausea in pregnant women.
It became apparent in the 1960s that thalidomide treatment resulted in severe birth defects in thousands of children.
“Thalidomide is a known human teratogen and carries an extremely high risk of severe, life-threatening birth defects if administered during pregnancy.”
effects of exogenous teratogens
Can result in Fetal Alcohol Syndrome (FAS)
Causes intrauterine growth delay
Affects development of brain
Typical facial features include small cranium and jaw, thin upper lip
Reduced mental processes, low IQ
FAS ?
via exogenous teratogens
thin upper lip
can be via exogenous teratogens
