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Time

The Common Vein copyright 2007

“Time is of the essence.”

Time is an abstract yet basic concept that defines the existence of every human being and the world in which they live.  Everything we experience ? from music and the formation of relationships to embryologic growth and the disease process ? occurs in time, making it an inescapable and defining element of our existence.  The study of medicine, too, is largely concerned with the passage of time, as a great many physiological cycles and developmental and aging processes occur from second to second, hour to hour, month to month, and year to year.  The images presented below are intended to convey the centrality of time in the study of medicine and biological processes.

Life time – 3 Images

Time – From Fetus to Adult to Old Age   The first image represents a fetus that is 6 weeks old taken in utero using ultrasound. The fetus is a 3.8mm long structure and by this time the heart is beating and is fully formed. It is surrounded by a gestational sac of amniotic fluid (black) The middle image taken along the Charles river in Boston shows a person who is about 20 in the the prime of individual expression, walking upright and with a mission. The last is of an old man taken in Trafalgar square in London- relaxed observing and in the latter end of his years.
fetal pole size dates time 6 weeks USscan obstetrics gestational sac amniotic cavity pregnancy Davidoff MD 84286p.800 49786b01 
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Life time – 3 Images da Vinci

 

da Vinci and Time
Three images by da Vinci showing the fetus, babyhood, womanhood and old age.
54860 Grotesque Profile, c. 1487-90 Leonardo da Vinci man aging elderly chin teeth edentulous nose hooked skin wrinkled muscle wasting hair loss anatomyLife time – 6 Images

Life Time – 6 Images

9 months and then a Lifetime
These 6 images look at time from a more embryonic perspective, from the time of conception (top left) where sperm meets egg, through the multiplication of cells as the blastocyst evolves, through fetal development as the primitive tissues evolve into a fetus attached by an umbilical cord (top right), a fetus flexed in the amniotic cavity with fully formed organs, a boy in full extension in his stride, and an old man who has been through a number of life cycles at the latter end of his life cycle.
13275b01i01e12u08 Davidoff oneness

Time in Structure

All the structures of the body will theoretically have a time zero at the moment the sperm fertilizes the egg.  From then on structures will  grow, mature, will be subject to the joys and wraths of time, and hence will change,  and then all will die.

There are both linear and cyclical elements that relate to the way structure relates to time.  Some structures will grow in size with time, such as the long bones of the body, and some structures like the ovary will undergo cyclical changes with time.  These will both be explored in the discussions below.

Growth

The growth phase for some tissues is phenomenally fast.  Fetal brain tissue for example is said to grow at 250,000 nerve cells per minute.  The heart starts out as a microscopic blob of mesoderm, a primitive embryonic tissue. Deeply embedded in the genetic makeup of the human form, there are codes that will direct the mesodermal blob to develop from a straight tube to a complex beating pump in 5-6 weeks.  At that time it will have the ability to connect to all parts of the body which at the time is a mere 3-4 mm long.  By this time it is a 4 chambered mature organ. From then on its growth is mostly a change in size in order to adapt to the increasing size of the body.

Heart Development
By 5-6 weeks the mature structure is developed
The heart starts out as a blob of mesoderm, and progresses through a straight tube phase, loops (usually to the right) twists, septates, and becomes a 4 chambered structure by 5-6 weeks.
01477b03 heart cardiac straight tube primitive heart embryology Davidoff art drawing Davidoff MD  15009c cardiac heart coronary artery normal anatomy gross pathology LAD diagonal artery acute marginal artery conal artery arc of Vieussens Courtesy Ashley Davidoff MD
TheCommonVein.netSome bones on the other hand, continue to gow for many years, and will  have unfused growth plates till the early twenties.  The long bones of the body, like the femur and humerus are examples. The growth plates (aka epiphyseal plates ) at either end of the long bones are made of cartilage.  They continue to evolve and grow by mitosis until they finally ossify at maturity.   While growing, the cartilage cells in the region called chondrocytes, age and degenerate. Osteoblasts move in and ossify the matrix to form bone. This process continues throughout childhood and the adolescent years until the cartilage growth slows and finally stops. When cartilage growth ceases, usually in the early twenties, the epiphyseal plate completely ossifies so that only a thin epiphyseal line remains and the bones can no longer grow in length. Bone growth is under the influence of growth hormone from the anterior pituitary gland and sex hormones from the ovaries and testes.

The humerus serves as a skeletal guide reflecting maturation from adolescence into adulthood.  The distal growth plate is the first of the long bones to unite, while the proximal growth plate is the last of the growth centers to unite.  This occurs at about 18-20 years.  The growth plates of the iliac crests fuse a little later (early twenties) while the sutures of the vault may close beyond that age.

Epiphyses at the elbow of an 11 year old
The X-rays of an 11 year old child reveal unfused ossification centers of the distal humerus, proximal radius, and ulna.  They appear as unfused “fragments” but are really cartilagenous areas that progressively ossify during growth until they ossify completely and fuse at maturity.  The distal humerus is the first of the long bones to unite.
73590c01.800 11 years old with ossification centers elbow humerus radius ulna bone normal anatomy ossification centers 6 ossification centers around the elbow joint. appear at different ages or fuse. the ossification centers always appear in a specific sequence. mnemonic of the order of appearance of the individual ossification centers is C-R-I-T-O-E: Capitellum, Radial head, Internal (medial) epicondyle, Trochlea, Olecranon, External (lateral) epicondyle. as a general guide, remember 1-3-5-7-9-11 years.
Ashley Davidoff MD TheCommonVein.net

Even though bones stop growing in length in early adulthood, they can continue to increase in thickness or diameter throughout life in response to stress from increased muscle activity or to weight. The increase in diameter is called appositional growth. Osteoblasts in the periosteum form compact bone around the external bone surface. At the same time, osteoclasts in the endosteum break down bone on the internal bone surface, around the medullary cavity. These two processes together increase the diameter of the bone and, at the same time, keep the bone from becoming excessively heavy and bulky.

 

Young and Aging
Normal changes in the skin over time as a result of loss of elasticity of the tissue.

49609c03 abdomen health disease young old time cycle elastic elasticity order disorder Davidoff MD 49609c02

In the cardiovascular system early “normal” atherosclerotic changes are seen as early as 18 years and the macroscopic result is is called fatty streaking.  This is due to normal wear and tear and causes no harm or disease at this time.  It is purely an early “wear and tear” on a structure that is undergoing expansion and relaxation about 60 times a minute, (conservative estimate since during sleep heart rate is slower), 3,600 per hour, 217,728,000 per year,  4,354,560,000 after 20years, and 15 billion by 70 years.   Thus wear and tear changes should not be unexpected and are considered “normal”.  However in the presence of other factors like hypertension, dietary and behavioral indiscretions, or genetic factors, the degenerative process is accelerated and diseases such as aneurysms and obstructions can occur.

Atherosclerosis
This image shows three pathological specimens of the aorta. In the first image minimally raised fatty streaks are noted. (a)  This is a normal “wear and tear” finding and can be seen as early as 18-20 years. In image b, the fibrous capsule causes raised fibrofatty nodules.  This is also a normal appearance, and would be seen in the aorta of a 60-70 year old.  In c, there is severe atherosclerosis, more than expected for wear and tear, and this is pathological.  There has been rupture of the plaques, resulting in friable atheromatous plaques.

Courtesy Henri Cuenoud MD 13420c

Life Cycles

Some biological units like the patelet will complete a life cycle in a mere 10 days.  The red cells have a life span of only 120 days after which time they are removed from the circulation, broken down by the spleen and parts are either excreted or reused in some form.

All the ova of an individual (400,000) will be “born” with the ovary and will remain latent till female maturation.  Only about 450-500 will reach maturity during the reproductive life of the female.  Each month during the years of reproductive capability, one ovum will reach maturity and will be deployed for potential fertilzation.  The ovum will last 12-24 hours and will either end its cycle if not fertilized, or go onto an exciting roller coaster ride for the next 70 years or so if it is fertilized.  This process continues till menopause.

Follicles in a Reproductive female – Cyclical Phases
This ultrasound image shows 5 developing follicles in the right ovary that are all less than 1cms at this stage.  (black cystic structures)   One of these will progress to ovulation and will release its ovum when the follicle becomes about 2cms.

71689 ovary follicles normal anatomy function physiology TCV Applied Biology Cycle time USscan Davidoff MD

 

Mid Cycle Ovulation and The Formation of the Corpus Luteum

 
In the first image the irregular black cavity represents the cyst that has ruptured and released its egg.  In the second image, the red and blue ring surrounding the irregular cavity of the ruptured cyst (called a corpus luteum cyst) represent the blood supply that enables the cyst to stay alive.  If the the ovum is fertilized then the corpus luteum becomes a transient endocrine organ producing hormones to support early pregnancy and it is then called a theca lutein cyst.  If there is no pregnancy then the life cycle of the corpus luteum ends and it dies and undergoes fibrosis.

60654c01 60654c01 ovary mid cycle fx cyst with irregular crenated border ring of fire inflammation hyperemia ovulation ovum dx corpus luteum cyst USscan doppler Davidoff MDAC

 

Corpus Luteum Cyst – Ovulation from Both Ovaries
The CT scan of this patient  shows white rings around a gray structure in both ovaries.  They represent corpus luteum cysts as seen on CT scan with the white ring representing the blood flow seen in the US above. In (a) the white ring is seen in the right ovary, and in (b) the ring is seen in the left ovary.  Image c is an enlarged version of (a) and image d is an enlarged version of (b).

Thus in this person two follicles have developed simeltaneously – a distinctly unusual situation.  Both have matured, ruptured, and have provided two ova available for fertilization.  This situation is a set up for non identical twins (aka fraternal or dizygotic)  if both ova are fertilized.  About 1% of births are of this nature – ie fraternal twins.

46693c01 ovary ovaries pelvis bilateral ring of fire corpus luteum cysts normal physiology potential for twins anatomy applied biology Davidoff MD

Size as a Measure of Time

 

Since biological structures grow with time, measuring length of structure and comparing this length against the normal established  standards, enables biologists and physicians to age structure.  The use this principle is applied to the aging of a fetus in the field of obstetric ultrasound.  In the early phases of pregnancy, the crown-rump length is used. As the fetus ages, structures such as femoral length, biparietal diameter, and abdominal circumference are not only used to predict the age of the fetus but also its potential weight. A series of ultrasounds of a particular pregnancy will allow the physician to assess growth and well being since if the expected growth pattern falls off the normal, then a disorder called growth retardation will be considered.

3.8mm fetus  – 6 weeks
49786b01 fetal pole size dates time 6 weeks USscan obstetrics gestational sac amniotic cavity pregnancy Davidoff MD

 

Growth of the Femur
Image a shows an ultrasound of a fetal femur which measures 33.00 mms in length.  This length corresponds to a fetus who is 20weeks and 2 days old.  The second image is of a 60 year old patient with a femur that measures 600mms.  Full length of the femur is reached at about 20 years.

48395c01 bone femur femoral length fetus adult age aaging time growth normal Davidoff MD

Time in Biologic Function

It has often astounded me throughout my medical education how many hours a premedical or medical student may put into gaining mastery of a process that occurs in a mere matter of seconds.  One example of this is the action potential, the impulse that arises from the rapidly coordinated opening and closing of sodium and potassium channels in the neural membrane.  This event, which occurs in fraction of a second, is a defining one in human function, as it is the basis of the nervous system and all sensory and motor control.  The summation of action potentials to convey more coordinated impulses and more detailed information to and from the CNS is also critical to proper physiologic functioning and, incidentally, serves as yet another example of units to unity.

 

Time in Biologic Function

It has often astounded me throughout my medical education how many hours a premedical or medical student may put into gaining mastery of a process that occurs in a mere matter of seconds.  One example of this is the action potential, the impulse that arises from the rapidly coordinated opening and closing of sodium and potassium channels in the neural membrane.  This event, which occurs in fraction of a second, is a defining one in human function, as it is the basis of the nervous system and all sensory and motor control.  The summation of action potentials to convey more coordinated impulses and more detailed information to and from the CNS is also critical to proper physiologic functioning and, incidentally, serves as yet another example of units to unity.

Sodium Pumpand Potassium Diffusion Process in the Creation of an Electrical Path fo the Transmission of Neural Impulses
72045b04.800 nerve conduction force electricity electric force positive force negative force sodium pump Na pump Patassium pump K+ pump diffusion conduction of impulses Davidoff drawing Davidoff art Davidoff MD

Perhaps one of the most important ways in which action potentials manifest themselves is in the regular, coordinated beating of the heart.  Equipped with its own pacemaker, the SA node, the heart experiences regular contractions of its atria and ventricles about every second such that blood may be continually pumped through the body.  The rapidity with which the SA node issues electric impulses is, in turn, responsible for the second-to-second changes in the shape and width of blood vessels, which expand and contract as blood pulses through them.  However, the cardiovascular system is but one illustration of the complex functions that may be achieved along the order of seconds.  Countless chemical reactions occur with astounding speed at such critical locations as the active sites of enzymes, cellular organelles, and the interiors of each organ, such as the liver.  The images below serve as illustrations of some of the aforementioned processes.

Changes per Second

EKG  – Electrical Impulses
The EKG reflects the electrical activity of one heartbeat and consusts of a p wave, a QRS complex, and a t wave.  This event takes place in about 3/4 of a second in this instance.

71679 heart cardiac electrical activity electricity force p wave QRS complex STsegment T wave normal EKG Laboratory Davidoff MD

In the above example the EKG shows the time over which the electrical activity occurs through one cardicac beat.  Each small square is .04seconds or 40 miiliseconds.  The p wave is the depolarisation process of the atria and in this instance it takes just under 3 squares or .12seconds or about 120 milliseconds.  (normal adult (120-200msecs)  The QRS complex is the depolarisation process of the ventricles and it takes about 80 milliseconds.  (normal adult (60-100 milliseconds)  The ST segment is an isoelectric period and takes about 320 milliseconds.  The T wave is a repolarization process.  The end of the T wave to the beginning of the p wave and a new cycle is about 200 milliseconds in this instance.  Thus with a person at rest, the total cycle is about 750 milliseconds.  The biochemical events that bring this about are occurring in nanoseconds while the electrical manifestations of depolarisation and repolarisation are measured in subsecond time- ie milliseconds.

Wigger’s Diagram of a Single Heart Beat
The Wiggers diagram reflects the effect of one heart beat on the pressures in the aorta (teal) the left ventricle (orange) and the atria (royal blue).  The elctrical activity that enables the heart beat is seen in the EKG tracing (pink) and the changes as may be heard by a stethoscope are seen in light green with S1 being the first heart sound (valves opening) and second heart sound (S2 = valves closing).

33808b.800 heart cardiac physiology pressure EKG ECG pressure curves diagram LV aorta LA left atrium left ventricle systole diastole acv waves Davidoff MD

 

Pulsation in the Aorta

Change in Size Shape and Character as a Single Pulse Beat Goes through the Aorta – about .75 seconds in the resting state
This image of the theoretical functioning of the role of resistance and outflow enabling the infrarenal aorta to function as second pump. In systole (b) the suprarenal artery is expanded by the pulse but is relatively decompressed by the the low resistance and high flow renal arteries. The infrarenal aorta is relatively more expanded in systole (b) since the iliac arteries offer a relative resistance. This increased resistance causes the elastic tissue in the aorta to stretch (b) so that the recoil in diastole (c) results in a sustained forward moving force assisting the blood to get to their most distal destination – the feet. Courtesy Ashley Davidoff MD. 24877c03

Rhythmic Pulsations of the Cardiovascular System

Journey of a Single Red Cell
With the one heart beat a red cell will start on its journey.  If it is on the left side of the heart it will be ejected into the systemic circulation and it will begin on a journey with the purpose of delivering oxygen and bringing back carbon dioxide to the the right side of the heart.  It will travel through a series of arterioles and capillaries until it reaches its destination.  It will then give up its oxygen, exchange it for carbon dioxide, remaining in the capillary for a mere 1-3 seconds, and then return via venules and veins to the right side of the heart, about 1 minute later. When the heart rate is faster as during excercise the journey will be much faster.

Courtesy Ashley Davidoff MD 32059 code cardiac heart circulation artery vein introduction drawing Davidoff art

 

Air in a Tampon

Time of the Month
37 year old female with tampon overlaid in green in image b.  Menses is implied

endometrial cycle normal uterus USscan Courtesy Ashley Davidoff MD Copyright 2009 all rights reserved

83626bc01.8
Immediate Post Partum (a,c) and 18 Months Later (b,d)
The CTscan is from a 26 year old female who presents 18 months after a cesarian section with pelvic pain.  Image a was taken immediately after her deliveryand shows enlarged breasts with prominent glandular tissue, and image b is taken 18 months later where the breasts have reurned to their smaller basal and resting state.  Image c shows the rounded large uterus in the pelvis just after the cesarian section and it also returns to its normal size in d, (white contrast enhanced structure)18 months after delivery.

CTscan Courtesy Ashley DAvidoff copyright 2009 83354c.8s
Immediate Post Partum (a,c) and 18 Months Later (b,d)
26 year old female presents 18 months after post c/section. Image a taken at the time of the cesarian section shows prominent glandular tissue in the enlarged  breasts, while image b shows the breasts in their normal smaller basal (resting) state 18 months later.  Image c shows the enlarged rounded uterus immediately after delivery of her baby by cesarian section, while image d, shows the smaller uterus 18 months later.

the enlarged uterus just after cesarian sectionHer breasts 18 months later show the glandular tissue is decreased compared to the immediate post partum period .

CTscan Courtesy Ashley DAvidoff copyright 2009 83354c.8s

Of course, proper physiologic function is not defined solely by the rapid activity one sees in chemical reactions and action potentials.  Many processes, such as mitosis and meiosis occur in a matter of minutes and hours, depending on the organism.  Certain bacteria, for instance, are capable of doubling and re-doubling their population in hours under ideal conditions, allowing for the rapid rise of infections in humans and other organisms.  Cellular division is also essential in humans, where it occurs more slowly and underlies the processes of healing, tissue regeneration, and gametogenesis.  Even respiration, another fundamental physiologic function, may be tracked according to the volume of air inspired over time, as illustrated below.

Time and the Respiratory System
This diagram represents a single cycle of respiration.  The lungs expand on inspiration.  At rest this takes about 2 seconds.  They return to thir base line relaxed stae with expiration which takes about 3 seconds.

42530b05b09b14  Davidoff art

Biological cycles are also intrinsically tied to the passage of minutes and hours, as they are defined by the occurrence of chemical or electrical events in regular intervals of time.  For instance, ovulation and the menstrual cycle involve the precise and predictable adjustment of hormone levels over a certain number of days, such that any female experiences regularity in her reproductive cycle.  In this way, the varied implications of biology as a function of time become clear.

  

Time in Disease

 Just as our understanding of physiologic processes is informed by assessing them in the context of time, so is the passage of minutes, hours, and days critical to understanding diseases and their progression within the body.  Indeed, one of a physician?s primary responsibilities, diagnosing illness, is accomplished by assessing symptoms as they have occurred within a particular timeframe and subsequently classifying the illness as mild and in its early stages, advanced and potentially life-threatening, or somewhere in-between.  For instance, the character and size of a malignant tumor, is important for classifying the progression of the cancer that caused it.  A small, immature tumor may indicate an early, treatable stage of disease while a large, tumor that has had time to metastasize presents as a more serious, life-threatening stage of cancer.  This serves as just one example of the central role a working knowledge of time and disease may play in the everyday work of a physician.

            Before delving into examples of disease processes it is important to realize that every physiologic system (Circulatory, Respiratory, Digestive, to name a few) is characterized by its ability to execute events both instantaneously and over longer periods of time. The immune system, for instance, is capable of very quickly initiating inflammatory responses through the rapid release of histamine from mast cells, leading to anaphylaxis in serious cases.  This occurs within a few seconds of the initiating event.  On the other hand, this same system?s primary response to a bacterial or viral infection relies largely on the steady mounting of antibodies against the invading pathogen over a period of days.  Similarly, diseases and disorders that afflict our physiologic systems may occur within seconds or across days and years.  For instance, some disorders of the circulatory system, such as heart attacks due to acute coronary thrombosis, may afflict their victims within seconds while others, such as atherosclerosis, develop over years.  Thus, it becomes apparent that physicians must establish a working knowledge of disease as it relates to time in order to effectively diagnose and treat patients.

Disease Measured in Seconds, Minutes, Days, and Years

As anyone familiar with work in the emergency room knows, a variety of serious conditions can develop in a matter of minutes such that rapid response and treatment is absolutely essential to preserving the life of the afflicted patient.  Anaphylaxis, acute coronary thrombosis, and pulmonary embolism can all act within seconds to compromise essential physiologic functions, sometimes so severely that death becomes imminent without immediate treatment.  Indeed, the rupture of an aneurysm or the blockage of a blood vessel or airway for even a short period of time can cause catastrophic and sometimes irreparable damage to the body.  Loss of consciousness can result from anoxia in about thirty seconds and brain damage results not too long after this.  Still other diseases, such as influenza and bacterial infections, do not become fully manifest until days after initial exposure to the pathogen, and HIV, one of the most virulent viruses on the planet, may remain latent within the body for up to ten years.  Thus, understanding the timeframe within which symptoms of particular diseases typically appear is both daunting and critical to accurately diagnosing the signs of illness patients present with in clinical settings.

 

Normal – 4 months Prior and Following Cardiopulmonary Arrest

Loss of Gray White Differentiation
7After 5 minutes of cardiopulmonary arrest the brain has lost its characteristic markings due to the damage of the brain cells and edema.

0134c01 hx 52 F post cardiac arrest brain cerebrum gray matter white matter gray white differentiation gray white distinction sulci gyri loss of gray white differentiation hypodense dx anoxic injury with diffuse global cerebral edema Davidoff MD Loss of consciousness occurs within 10-15 seconds of cardio-pulmonary arrest. Irreversible brain damage can occur within 5 minutes. gray matter of the brain, particularly the frontal lobes have highest metabolic needsThe occipital, parietal, and temporal lobes and basal ganglia and cerebellum are lower. brainstem lowest needs

Time and Diagnosis

  The diagnostic process is a three part process.  Acquisition of data, processing the data, and then interpretation of the data.  This is true whether it relates to the clinical environment, lab tests, or imaging tests.   A clinical evaluation may take 30-45 minutes, and sometimes it is all that is necessary to come to a diagnosis.  An example of this may be a disease such as asthma.  On other occasions the diagnosis is made once routine tests such as routine blood tests, EKG and or chest X-ray are added.  Pneumonia is such an example when a consolidation is found on a chest X-ray.  The acquisition of the data  for a chest X-ray is short (measured in seconds) processing time (perhaps 30 seconds).  The data is sent to a work station where it waits in line to be read by the radiologist.  Once it reaches the front of the line, interpreation takes a few minutes.  Communication time can range from an immediate phone call, fax, or electronic report (minutes) to typed report correction and fax (about 24 hours)

If after the clinical presentation and routine studies the diagnosis still eludes the physician, then special directed diagnostic studies are required.  A patient who presents with fever and a neck mass will require a CT scan.  This study takes about 10 seconds to acquire the data, about 30 seconds to process the data.  The processed data is then placed onto a work list for interpretation by the radiologist and is interpreted within 1 or 2 hours.  If for example multiple enlarged nodes are seen a variety of diseases can be suspected and a differential diagnostic list is created but a biopsy is required for further workup.  This of course will occur on another day and another time and the biopsy will be performed by a surgeon or a radiologist using imaging guidance.  The material is submitted to a pathologist who has to process the material, and examine the material under a microscope, and render an interpretation.  This usually takes about 24 hours but even at this level further staining to delve deeper into the diagnosis may be required.

The goal is to make an accurate diagnosis as soon as possible.  The next goal is to initiate treatment as soon as possible.  A patient who has chest pain and is diagnosed with acute myocardial infarction in a timely fashion, should be referred to the cardiac catheterization laboratory for consideration for thrombolysis.  If the findings suggest thrombus in the coronary artery, then treatment with thrombolysis can be initiated immediately.  The time between diagnosis and treatment is minutes.

Another aspect of time and diagnosis is the determination of the acuity of a disease process using imaging.  If a patient presents with a focal neurological deficit and the question of an acute stroke is raised.  MRI with diffusion weighted imaging can differentiate between an acute process or a chronic process.  Timing of the disease has significant implications in the treatment that may be employed.  An example of the difference between an acute and chronic infarction in the brain is shown below

Acute Infarction – Loss of Brownian Motion

Chronic Infarction Changes in Volume
The CT scan on the left was taken after the patient presented with acute focal deficit.  It  suggests bilateral subtle abnormalities in the occipoital lobes.  The MRI shows that the findings on the right side in the diffusion weighted sequence (right image) with intense brightness is diagnostic of an acute process, while the finding in the left occipital lobe are unrevealing suggesting that they are of a chronic nature.

49679c01 brain DWI occipital lobe fx vague hypodensity right occipital lobe with encephalomalacia and ex vacuo changes in the left occipital and posterior parietal region dx acute infarction right occipital lobe chronic infarction left occipital lobe CTscan high intesity in right occipital lobe and low intensity in left occipitoparietal region dx acute infarction right occipital lobe chronic infarction left occipital lobe MRI diffusion weighted imaging Courtesy Ashley Davidoff MD

 Time in Treatment

It is important to realize, that treatment of diseases also occurs over a specific time frame and requires knowledge of how certain drugs and therapies function over time.  A patient in ventricular fibrillation can be converted by an automated external defibrillator in seconds, and a patient who has anaphylaxis can recover within a minute after receiving epinephrine, either subcutaneously or intravenously.  Medications given intravenously will become effective quicker than those given orally.  However an antiobiotic given intravenously will only be effective when a critical balance is overcome that enables the body to dominate the infection.  This may be hours in coming.  Other drugs such as sedatives and anxiolytics only require the time to reach their target organs in order to take effect.  This is usually about 30 seconds.  Oral medications have to be absorbed into the circulation for systemic effects.  Some medications are absorbed by the stomach and the time to become effective is less than those that are absorbed in the small bowel.

Other aspects of time to be considered relate to how long the drug is effective.  In pharmacology terms the half-life of the drug reflects the duration which a drug may be active, since half life is defined as the time that is required for half of the drug to be removed either by physical or chemical means.  Some drugs like epinephrine are short lasting (minutes) others last for hours (insulin), while others are effective for days (coumadin and digoxin).  Subcutaneous depot medroxyprogesterone acetate which is a subcutaneously injected contraceptive for females is injected every 3-4 months.

Narcotics and steroids, for instance, are often prescribed for a limited amount of time, as prolonged use of either one may result in addiction or other undesirable physical effects, respectively.  Other treatments, such as birth control pills to manage an endocrine disorder or medication to combat autoimmune disease, are necessarily taken for prolonged periods of time.  Chemotherapy, depicted in the image below, is of the latter category, as it is often completed over many months to rid the body of malignant cells.

 

Before and After Chemotherapy

Regression of Metatstatic Liver Disease
The  CT scan in image a shows an enlarged heterogeneous liver with multiple hypodense nodules representing metatstatic small cell lung deposits.  6 weeks after the introduction of chemotherapy a CTscan b shows complete resolution of the malignancy in the liver.

70248c01 liver metastattic small lung carcinoma with diffuse metatstattic disease to the liver )hepatic metastases metastasis before and after treatment 6weeks post chemotherapy successful result size change character change CTscan Davidoff MD 5star

So, as has been illustrated here, what makes time so fundamental to human physiology and disease is that it defines a broad spectrum of bodily process, whether life-giving, life-maintaining, or life-ending.  The effective practice of medicine, then, relies upon a mastery of these concepts and a continual appreciation for the centrality of time in determining the health outcomes of one?s patients.

Prior Link to all Life  The Umbilical Cord That Was
49703b17c01.801 body in 12 moods umbilicus abdomen a day in the life a year in the life Davidoff art

Reference

The Locomotor System Dartmouth.edu