Form and Function

Since we've been talking and reading about reflexes I thought I'd write a little about the hyper-reflex in pre-eclamptic women known as clonus but have been able to find much less online information than I'd like. I thought the internet knew everything! Maybe I'm just not putting in the right combination of search words, but I'll include what information I have been able to find.

Clonus is the repetition of involuntary muscle contraction and relaxation that occurs in response to a rapid stretching of the muscle. It is most commonly tested in the ankle by a quick manual dorsiflexion of the foot. If the foot repeatedly plantarflexes/dorsiflexes in response to the test, the individual is said to have a positive sign for clonus. If this sign is present in the non-pregnant person it indicates a CNS problem which may include MS, ALS, Huntington's disease, or spinal cord injury among others. In the pregnant woman it generally occurs along with other signs of pre-eclampsia such as high blood pressure and proteinuria. Unfortunately this is where the extent of the useful information I've been able to find generally ends. I was hoping to find an explanation of the exact mechanism that causes this sign in relation to pre-eclampsia but mostly find only vague references to "hyperreflexia", "reflex irritability", and "CNS involvement". The best deduction I've been able to make is that clonus is a result of the hypertension that occurs with this disorder which can cause vasospasm, edema, and ischemia in the brain. Surely this would qualify as "CNS involvement". Much of the pathophysiology of pre-eclampsia and eclamptic seizures is unknown and several theories exist as to the underlying cause.

I'm totally embarrassed that only today did I have what Oprah would call an "aha moment" about the Na⁺/K⁺ pump as it relates to a cell's resting membrane potential. I've been going along with the nagging question, "If the pump is moving two postively charged ions, how does this result in a negatively charged cell?". Well today I have the answer (thank you Figure 11.8). More K⁺ than Na⁺ passes through leakage channels, down the gradient created by the pump, thus creating a net negative charge!

Moments like this make me wonder to what extent my educational history could be summed up as, "Memorize stuff. Comprehension is optional." Maybe I should have a shirt made.

One of my TV channels is Discovery Health which brings a lot of interesting shows my way. Recently I watched one on Twin to Twin Transfusion Syndrome which was interesting because I know probably less than I should about multiple pregnancies. So I'll start here with the most interesting (to me) part of identical twin embryonic development, specifically the way in which the number of days post conception at which splitting occurs affects various aspects of the twins' development. The listed "days post-fertilization" are approximate.

* If the zygote splits 1-3 days post-fertilization, the twins will have separate placentas and amnions. All identical twins except this type are at risk of developing TTTS.

* If the split occurs 4-8 days post-fertilization the twins will share a placenta but will have separate amnions.

* If the split occurs 9-13 days post-fertilization the twins will share the placenta, chorion, and amnion, meaning that they live in the same amniotic sac during gestation.

* If the split occurs on day 14 post-fertilization or beyond, conjoined twins will result.

Twin to Twin Transfusion Syndrome occurs in about 20% of twin pregnancies where both babies share the same placenta. It is caused when blood flow from the placenta is shared unequally between the babies or blood vessels directly connect the babies' umbilical cords. Sometimes both conditions exist. One twin, the "recipient" will receive an excess of blood, straining the heart and resulting in an excess of amniotic fluid (secreted as urine). The "donor" twin has a very low blood volume resulting in slowed growth and a lack of amniotic fluid.

Treatments are few and are frequently unable to provide a positive outcome for both twins or even for one of them. The most conventional treatment is the draining, generally repeated, of the excess fluid that collects around the recipient twin. An alternative treatment, and the focus of the show I was watching, consists of intrauterine laser treatment to coagulate blood vessels that connect the donor and recipient twins in an effort to restore equal blood flow to both babies.

Oxytocin

How could I not write about oxytocin? As the "love hormone" and with many implications in birth and breastfeeding, oxytocin is near and dear to me. Oxytocin is both a hormone and a peptide-type neurotransmitter and is produced in the hypothalamus then moved to the pituitary where it is packaged into vesicles. Oxytocin is released when oxytocin cells in the hypothalamus send an action potential along their axons to the pituitary, signaling the pituitary to release the contents of the oxytocin vesicles into the blood plasma by means of exocytosis. Oxytocin, along with vasopressin, are the only hormones to be released at such a distance from the locations where their effect occurs. I suppose it's obvious that this allows synthetic forms of oxytocin such as Pitocin to create uterine contractions when administered by IV or intramuscular injection in the leg, but I'd never really thought of it specifically so I'm finding it interesting. Oxytocin is received by specific oxytocin receptors that are necessary for oxytocin to enter the tissues of the body and produce its intended effect. I found information on pharmaceuticals that act as oxytocin receptor antagonists used for preventing pre-term labor, but no information on whether any type of anagonist is naturally produced in the body. I've suspected that there is simply because I've seen Pitocin given to women in late pregnancy with no effect. No contractions, nothing. Given that oxytocin, in combination with other hormones, is largely responsible for mother-infant bonding immediately after birth, it is probably obvious that there are concerns both about the use of synthetic forms of oxytocin used in birth as well as postpartum care routines that distract the mother from her baby or separate the baby from the mother. Quoting renowned French obstetrician Michel Odent regarding generation of the oxytocin peak that occurs immediately after birth*:

"It is easier if the place is very warm (so that the level of hormones of the adrenaline family is as low as possible). It is also easier if the mother has nothing else to do but look at the baby’s eyes and feel contact with the baby’s skin, without any distraction." and "In the particular case of the hour following birth, in physiological conditions, the high peak of oxytocin is associated with a high level of prolactin, which is also known as the "motherhood hormone." This is the most typical situation for inducing love of babies."

Dr. Odent has an entire book dedicated to the subject of the hormones of birth, breastfeeding, and mothering, titled The Scientification of Love, and hopefully some day I'll get around to reading it.

Histamine

Histamine is an amine-type neurotransmitter that plays roles in immune function, smooth muscle contraction, gastric acid secretion, and vascular permeability. Most histamine is produced and stored in mast cells, particularly in areas where injury is common such as the nose, mouth, feet, and blood vessels. A small portion of the body's total amount of histamine is stored and is active in the brain. When histamine is released it can bind with one of four histamine receptor types. The H₁ receptor is the classic type we think of when we think of histamine, resulting in allergic reactions such as difficulty breathing and hives. This type of receptor is found in smooth muscle, endothelial tissue, and in the brain. The H₂ receptor is found on parietal cells and causes gastric acid to be secreted. The H₃ receptor inhibits release of the neurotransmitters histamine, acetylcholine, norepinepherine, and serotonin. The H₄ receptor is found in the small and large intestines as well as in the thymus, spleen, bone marrow, and basophils. Its function is unknown. After being released, histamine is broken down by the enzyme acetaldehyde dehydrogenase. (I thought this next part was interesting because it goes against common assumptions.) It is not an excess of histamine that is responsible for heightened reactions to common allergens, but a deficiency of acetaldehyde dehydrogenase.

GABA

Gamma-aminobutyric acid (GABA) is an amino acid that acts as the primary inhibitory neurotransmitter in the adult human brain. In some other species or in the immature human brain GABA has a primarily excitatory effect. GABA receptors are found in the membranes of both pre- and post-synaptic neurons. To produce an inhibitory effect, when GABA binds to its receptor sites, either Cl^- flows into the cell or K⁺ flows out, causing hyperpolarization of the cell membrane, and making it more unlikely that an action potential will be fired by that neuron. GABA has more than one type of receptor and many drugs produce their effects by interacting with these receptors. Benzodiazepines (e.g. Xanax, Valium, Rohypnol), for example, bind the alpha and gamma sites of the GABA_A receptor, resulting in sedation, muscle relaxation, decreased anxiety or other effects depending on the specific drug. (I looked into this particular group further because I take small doses of Xanax to fly and thought maybe it would be a good idea to know what was going on in there.) Alcohol, barbituates, some anesthetics, and even the herb valerian also act as GABA agonists.

You Know You're in A&P When...

...You misread a business sign advertising "Crystal Gardens" as "Costal Gardens".
...You purchase Atlas of the Human Body by Vigue and Martin off the bargain racks at Barnes & Noble for its lovely anatomical drawings.

I've recently started reading the classic book Childbirth Without Fear, first published in 1942, and written by Dr. Grantly Dick-Read. This book first formalized the theory that pain in childbirth results primarily from the presence of fear in the birthing woman and first named the Fear-Tension-Pain Syndrome that is still commonly taught in prenatal childbirth classes today. I'm only a portion of the way through the book and only have his say-so on certain anatomical information presented as we haven't gotten as far as the uterus in class, but with the heavy emphasis on the importance of the state of the nervous system during birth, I thought the ideas presented in the book are relevant at this point. I will try to summarize the most important points as he presents them:

1. No other normal physiological process of the body is expected to be or is experienced to be painful. Only when bodily processess exceed physiological norms is pain experienced.

2. The parasympathetic nervous system controls the longitudinal muscle fibers that contract to cause the cervix to dilate and the baby to move down the birth canal. The sympathetic nervous system controls the circumferential muscle fibers that cause constriction of the uterus and restriction of the birth process. Also controlled by the sympathetic nervous system is the muscle tissue that surrounds the blood vessels serving the uterus.

3. In the absence of fear, the fight or flight response of the sympathetic nervous system is inactive, allowing birth to progress smoothly and according to the physiological norms of this body function.

4. In the presence of fear, the sympathetic nervous system cause the circumferential muscle fibers of the uterus as well as muscle fibers that surround the uterine blood vessels to contract, causing excessive muscle tension between the longitudinal and circumferential fibers as well as restricted uterine blood flow. These effects result in pain.

I'm rather impressed by the many ways Dr. Dick-Reads observations of modern obstetrics apply as clearly today as they did in 1942 and am greatly enjoying reading the detailed, original explanation that forms a primary foundation of the childbirth program I teach. A good read!