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Anatomy of Circadian Rhythms in the Body

Anatomy of Circadian Rhythms in the Body

Ashley Davidoff MD Copyright 2015

To every thing there is a season, and a time to every purpose under the heaven:

 A time to be born, and a time to die; a time to plant, and a time to pluck up that which is planted;

Ecclesiastes 3:1

What is a season?

A season in the classical sense, is a natural division of the year and relates to the position of the earth to the sun.  The sun is a source of light, warmth, and energy.  A season is a continuum of time divided by the rhythmicity of four seasons.   The seasons are characterized by changes in light and dark cycles as well as temperature cycles.  These factors impact life in all its aspects.

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Cycles Around and Within Us

This image shows the  seasonal cycle that occurs within a year.  The top left image is the spring when rebirth and restoration of life occurs.  The summer (top right) follows where light and temperature are high.  The mature mellow autumn follows with orange reds and yellow colors (bottom right) .  Light starts to fade and temperatures start to fall  Autumn is a time for introspection and recognition of mortality.  The bleak and cold winter follows with a silence of impending death (bottom left).  The dancers with their own cycles are incorporated into the larger cycle, inferring the intimate integration of internal biology with the changes in the environment.  They are positioned like the hands of a clock – again incorporating the element of time.

  • Spring is a time for birth, freshness and renewal
  • Summer brings energy, blossoming, productivity and maturation and is the prime of life. Light is brightest during this period and the weather is warmest
  • Fall brings mellowness and maturation and warns of decline.  Symbolically it is a time for introspection during mid life
  • Winter is the time of aging, bleakness, decline and death.  It is characterized by darkness and cold and symbolizes quietness, contemplation, and reminds us of our  impending old age and death.

“To every thing  there is a season”  What does that mean to the structures of the body?  

The changes of the seasons have parallels in the internal environment of the body down to the cells and molecules.  This implies that “everything” in biology experiences a season.  

The annual cycle of the seasons is experienced physically by the body, its organs, cells, and molecules throughout the year.  They sense the cold and the warmth, and the light and dark of the external environment.

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Seasons of the Feet

The AiA rendering is a collage of photographs with superimposed CT scan of the feet as they walk through the seasons.  The four seasons created in a sphere provide a sense of wholeness in time, while the footsteps represent a walk in  time.  The top left image of the sphere shows the magnolias of Spring, the next (going clockwise) is green forest of Summer, followed by the Fall and finally the deathly cold of winter.

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Seasons of the Abdomen

This AiA rendering shows the abdominal structures reflecting the seasons.  The spring is in shades of  pink, the summer in green of the forest and the blue of the sky, the fall in oranges and red, and the winter in ice blue and white.

Seasons within Seasons and Cycles within Cycles

The cycles of the body range from nano seconds per cycle to a lifetime.  Each cycle is part of another cycle.  Each cycle consists of a beginning that evolves to full speed production, progressing to a winding down phase and  finally a phase of rest and restoration. The Krebs cycle,  heart cycle, circadian cycle, menstrual cycle, are all part of the wheel within a wheel concept and in the grand scheme of a single life it revolves around the process  of  maturation.  These same cycles occur within the cycles of evolution with improvement in processes over time.

Biochemical cycles are responsible for growth, and reproduction. The clock has to be rewound, restored to step one so that it can do its duty again. All of these have been optimized by the grand Darwinian cycle of reproduction, generation after generation, picking up fortuitous improvements over the eons.

Seasons of the Day –  Parallel Changes in the External and Internal Environments

Seasons of the Body in a 24 hour Period

This image shows the parallel of a 24 hour cycle correlating with the seasonal cycle that occurs within a year.  The top left image is the dawn when the day is born and the person is restored from sleep and starts to get ready for the the next 12 hour period.  The stress hormones start to rise as the body prepares for the work day which reflects the summer time (top right) where light and temperature are high.  After the “summer” the mellow and introspective time of the sunset arrives(bottom right)  as light and temperature start to fade.  The temporary death of sleep provided by the night follows in the bottom left .

Daybreak at sunrise is the birth of the day, and represents spring time in the body.  We wake up restored while it is a little light and a little cold outside and are refreshed and reborn after our slumber.  As the day warms up, and the light becomes stronger, we enter the summer of our 24 hour cycle.  Our cortisol levels are up to deal with the physical stresses of the day and this preparation is felt in our cells and in our psyche.  As a result of the stress we are better able to process and produce at work.  During the day we reach the height of our wakefulness and are in our productive prime.    At dusk, the autumn of the day moves in as we start to wind down and become introspective.  The light starts to go down and without the sun, the day cools down. The winter of the day – nighttime arrives. It is colder and darker, and we prepare for sleep, a transient death that helps us restore.

The internal environment of the body also senses the cycles through a hormonal cycle called the circadian cycle, which is executed via the hypothalamus.   enabling rhythmic physiological and behavioral events of the body to work in parallel with the natural rhythms of the external environment.

“Anatomy of Sleep” 

The central control system for the circadian rhythms is in the suprachiasmatic nucleus (SCN) of the hypothalamus (turquiose blue butterfly shaped structure at the base of the brain)  It is responsible for the control of the circadian rhythms of the body.

Seasons of the Molecules

Circadian Rhythm and the Daily Internal Seasons of the Body 

There are three main physiological events in the daily human diurnal circadian rhythm; melatonin secretioncortisol secretion, and temperature variation.

Melatonin

Melatonin is secreted by the pineal body in response to the dark.  The retina identifies light and transmits this information to the suprachiasmatic nucleus (SCN) in the hypothalamus. The hypothalamus integrates the light and darkness cycles of the environment with the pineal gland which in turn secretes melatonin in the dark.  Melatonin levels are therefore high at night and low in the day.  Melatonin is involved in sleep cycles, blood pressure regulation, and in seasonal reproduction.

Cortisol

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Seasons at the Molecular Level in the Adrenal Gland

The adrenal gland is an essential component of the circadian rhythm.  It produces cortisol which prepares the body for the stresses of the day. The artistic rendering shows background of complex biochemistry artistically incorporated into the gland. This is a featured art piece  because of the beautiful manner in which the almost invisible gland transforms the biochemistry into life giving hormones.

Cortisol is a hormone produced by the adrenal gland that is elemental in the control of metabolic function. It prepares the body for impending stresses.  Diurnal secretion of cortisol is part of circadian rhythm physiology.  The level is highest in the early morning and is at its lowest level at about midnight to 4 am. This high level in the morning prepares the body for the stress of the day.  Cortisol is intimately involved in the metabolism of glucose, fat and protein.

Body Temperature

Body temperature is lowest about 2 hours before waking in the morning and highest in the late afternoon and early afternoon.  During the night metabolic activity is slowed and the lowered temperature is a mechanism to conserve energy.  temperature is elemental to all biochemical processes.

“Body Temp Variation” by user:RHorning – Image Source. Licensed under Public Domain via Commons –

Seasons of the Cells

The molecular changes give rise to cycles in the cells both in a minute to minute variations, hour to hour variations, and eventually into annual variations

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Seasons in the Squamous Flower

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Cycles in the Columnar Cell of the Colon

 

What would life be like if there were no seasons?

Although there is a pattern to the seasons – each one is different and as we gain perspective on the cycles.

There are cycles within cycles as time moves on – each not the same as the prior, but having many things in common.  The beginning of Spring is so full of life and we soon look forward and want to welcome the blooming of the brighter colors of summer.  And then the heat of summer comes and we look forward to the cool and mature fall – and the beautiful first deep snowfall comes and soon grows old, cold, uncomfortable and dreary – and the new cycle begins with our eyes a little changed

Eachseasons bring a lesson of life.  We need the seasons to feel the rhythm within us and around us… but each year the seasons are different, and we learn and grow with each season.

The dawn brings us newness and freshness.  The day brings us energy in full flight and productivity – the dusk brings quietness and satisfying mellowness and the night brings rest and restoration….   But each day is different, and hopefully we learn and grow with each day

“I think that to one in sympathy with nature, each season, in turn, seems the loveliest.”
― Mark Twain

“Life Cycle of the Uterus”

shows the uterus from birth through maturation to senility 

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Biological Rhythms

Biological Rhythms – Anatomy of the Fall- and Thanksgiving

Ashley Davidoff MD Copyright 2015

The Fall

Mixed messages.

Maturation with impending death.

Strong green,

Hints of orange, yellow, and red

Skulls and ghosts in gardens

Thanksgiving

Mortality and cycles of life

Biological Rhythms

“Early Fall”

shows a CT scan of a skull in the aging garden as the time of the Fall shows its beautiful head.  Some of the greens are still green but there is a sense of a cycle moving forward to a next phase as some leaves start to show their mature age with the coming of the fall season.

Time moves on

Yellows oranges and reds become deeper…

And more intense

And we understand George Eliot

Delicious autumn! My very soul is wedded to it,”

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“Mid Fall and Halloween”

shows a CT scan of a skull with reducing volume of bone as the Fall ages and becomes fatter.  The skull is located in the aging garden as the time progresses to the mature and mellow yellow, oranges, and reds.  There is a sense of a seasonal cycle moving forward. Middle fall is the season of Halloween when we are reminded of our mortality.

We take the dog for a walk

And everywhere it says

Death is coming

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“Autumn Reminding Us of Mortality”

shows the sentiment of the Fall as we move on in our life cycles.  Biology by its natural cycles will have a beginning, a middle and an end.  The fall is a time for contemplation and a reminder to make sweet while the sun shines.

Halloween brings the

Cutest of our society to say

“Do not to worry – there is youth in this season also”

And a pregnant Mommy stands behind smiling

Yet another inner maturation –

Cycles within cycles

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“An Autumn Beginning for this Baby”

shows an MRI of a pregnant uterus in the third trimester.  For this baby the fall is a beginning

So I come to think of the parts that make the whole

Of members of my inner society

And start with the cell

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“The Cell in the Autumn of Its Life Cycle”

shows the cell in the its own  mature and mellow colors in a background of yellows and oranges of the seasonal external cycle.  The beauty and reality of the seasons and biological rhythms are in us and all around us.

And think about the tree of my breath

As it goes through its cycles

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“Ginkgo Lung in the Fall”

is a rendering of a CT scan showing an upside airways forming the trunk and branches of a tree.  The lungs have been reshaped and colored  to reflect the shape of the ginkgo leaf in the Fall.

And about my aging bones that

Used to run in the park with no effort

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“Anatomy of a Jog  in the Fall”

shows X-rays of the calves of a runner taking a run through the park in the late fall season.  The orange colors reflect a mature part of a cycle as well as portray the element of time

and of the agility and beauty of a dancer in her prime

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“En Pointe in the Fall”

shows X-rays of the foot of a ballet dancer “en pointe” in the park in the late fall season.  The yellow colors reflect a mature part of a cycle as well as portray the element of time

 I try to shake off the melancholy

Uplifted by the performance ….

Through my orange eyes

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“The Dance of Autumn”

shows an impressionistic  portrayal of contemporary dance in the Fall.  The mature and mellow colors are reflected in the yellows and oranges with the occasional splash of evergreen green.

And then we give thanks

For being  alive

And for being part of a bigger family

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The First Thanksgiving at Plymouth, 1914

(Original by Jennie Augusta Brownscombe, Modified Public Domain Image )

 “Autumn carries more gold in its pocket than all the other seasons.”
― Jim Bishop

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Art of Anatomy of the Pancreas

Art of Anatomy of the Pancreas

Introduction

Ashley Davidoff MD Copyright 2015

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Pancreas in the Sky

is a photograph that shows a cloud formation embodying the shape of a pancreas

The anatomy of the pancreas is unusual and the physiology is multifaceted.  It is  a gland and is part of both the digestive and hormonal systems of the body.  Structurally it is characterised by its unusual shape and position and the absence of a capsule.  Functionally it is involved in the digestion of food as well as in the metabolism of glucose.  The most common diseases include pancreatitis, pancreatic carcinoma and diabetes. Serum tests, ultrasound, CT scan, MRI and endoscopy are most commonly used in diagnosis of pancreatic disease.  Treatment options include medical treatment (eg insulin in type 1 diabetes) minimally invasive procedures, and surgery.

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“Pancreas in Pink” 

is artwork derived from a CT scan and shows the upper abdominal cavity with the pancreas in bright pink surrounded by the liver, gallbladder, and kidneys. The aorta and inferior vena cava are the major transport vessels and serve to connect the organs.

Structure

Unusual Shape

“…and we stare in awe at your odd shape – why oh why did you choose that shape?
What are you supposed to look like? – we have no clue”  

from  “Hermit of the Abdomen” 

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Shapes of the Pancreas

The pancreas has been compared to many objects including an elongated comma on its side, an elongated number 9 on its side, a prism, a banana, an inverted and curved upside down tobacco pipe, and even an old fashioned revolver. Placing a seahorse or a woodpecker with head down and tail up probably brings us closest to the complex shape of the pancreas. The objects used for description are so varied and disparate, that one wonders if we truly have a grasp of the shape of this organ. A more practical way to look at the shape of the organ is to define the shape of its component parts.

Structure – Position

Deep in the Abdomen in the Retroperitoneum

The pancreas lies in the anterior pararenal space of the retroperitoneum surrounded by a vertebral body and kidneys posteriorly, the liver and gall bladder to its right, the spleen to its left, and the stomach and left lobe of the liver in front.  This AiA rendering shows the pancreas cycling through the seasons.  In the  spring it is in shades of  pink, the summer in blue, the fall in  red, and in the winter in ice blue and white. 

Function

The pancreas has dual functions in the the metabolism of the body.  It acts as an as both an exocrine gland (secretes into ducts) and an endocrine gland (secretes into the circulation).

As an exocrine gland it secretes enzymes into ducts that lead to the duodenum.  These enzymes aid in the digestion of fat, proteins, and carbohydrates. As an endocrine gland it is a key player in the control of glucose metabolism which it accomplishes by secreting insulin into the circulation.

The acini are the microscopic glands making up 98% of the parenchyma and they function as the exocrine component.

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“Blueberries of the Glands of the Pancreas”

is a rendering of the histological appearance of the pancreatic acinar glands. The artpiece  illustrates the ductules that subtends the acini  which are the exocrine glandular cells. The shape of the acinar cells and ductules are reminiscent of grapes or berries on a stalk.

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“Histology of the Glands of the Pancreas”  

The exocrine hormones of the pancreas that aid in the digestion of fats, proteins and carbohydrates are produced in the acinar cells in the glandular unit called the acinus.  The art piece shows the acinus with acinar cells and the duct that transports the secretions to the pancreatic duct and eventually to the duodenum where they aid in the digestion of proteins fats and carbohydrates.

The islets of Langerhans secrete insulin into the blood stream, very soon after ingestion of a meal in order to control blood sugar and intracellular glucose concentrations. The endocrine cells called the islets of Langerhans represent only 1-2% of the tissue volume of the pancreas, but play a vital role in body function and well being. They are most numerous in the tail of the pancreas.

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Islets of Langerhans

Immunohistochemistry on mouse pancreas for insulin shows the brown stained Islets of Langerhans that secrete insulin among the acinar cells.  They represent only 2% of the population of pancreatic cells. 

(Modified  Image –  Courtesy  Billyboy Wikipedia Public Domain)

Diseases

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Acute Necrotic Pancreatitis

This is a CT of an elderly man who had severe pancreatitis.  Within the retroperitoneum there is necrotic pancreas (asterisk).  It is enlarged and consists mostly of air (arrow), fluid, and high density hemorrhagic components.  The findings are consistent with a gangrenous pancreatic abscess.  The surgeon noted that the pancreas looked and smelled like a “dead fish…. that had been dead for quite a long time.”  Other structures including the gallbladder(gb), liver, kidneys, spleen and stomach surround the pancreas

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Pancreatic Cancer with Spread to the Liver

The CT scan shows a primary pancreatic cancer (red asterisk) with metastases to the liver.  Four of many metastases are identified with white asterisks

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Normal Pancreatic Cells and Pancreatic Cancer Cells

In the upper image the cellular makeup of the acinar cells of the pancreas manifest with a normal nuclear to cytoplasmic ratio reflecting the relative size of the nucleus to the cytoplasm.   The 2nd image show cancerous cells of the exocrine pancreas.  The blue nuclii are far too large for the amount of the cytoplasm of the cell (abnormal nuclear to cytoplasm ratio).  The malignant cells are also too dark (hyperchromatic) and lack uniformity and organization.  These are all features of malignant cells .  Cancerous cells do not obey the rules of the body and  have no regard for the body at large. Malignant cells are equivalent to rebels in the community. They destroy and do not contribute to the wellbeing of the society.  They also invade the territory of neighboring structures.

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Ravages of Diabetes 

The foot of a person with diabetes following amputation of the 2nd, 3rd, and 4th digits as a result of poor circulation of the tissues.  The magnified view shows the calcification and hardening of the arteries. 

Diagnosis

“Doppler Ultrasound of the Pancreas-Hermit of the Abdomen”

shows the pancreas in black in front of the splenic vein

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“ERCP – Ductal Skeleton of the Pancreas”

is from an ERCP with an injection into normal the dorsal pancreatic duct of Wirsung with contrast also noted in the distal common bile duct

“Arteries of the Pancreas”

is from an angiogram of the celiac axis and shows the multiple arteries that supply the pancreas.  The head of the pancreas is supplied by the  superior pancreatico-duodenal vessels which arises from the gastroduodenal artery,  and inferior pancreatico-duodenal artery which arises from the SMA.  The body is supplied by the splenic artery and the superior mesenteric artery.

Treatment

Treatment options include medical treatment (eg insulin in type 1 diabetes) minimally invasive procedures for drainage and relief of obstruction, and surgery.

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3D Nuclear Magnetic Resonance Structure  of Insulin Dimer

(Modified from public domain image from Wikipedia and Courtesy Jawahar Swaminathan Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute) 

“And then a bone guy – for God’s sakes – a bone guy! – called Banting and his student Best
exposed the insular chemistry of your insulin that had given you the power over the sweet
Never mind – in the end it was for the good of all –
And a new era was born 

from “Hermit of the Abdomen” Davidoff

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Pancreas and Buddies

This aquatic scene shows the relationship of the pancreas to its neighbours particularly the splenic vein and left renal vein which run a parallel course, almost like a bunch of buddies romping in the water.  The arching bodies with heads all in the same direction is quite beautiful

And then I think of you in your prime and in your happiness
When you are with your two buddies – the splenic vein and the renal vein
And you all look so much alike, and happy swimming in that deep ocean where you hide
And I wish this was forever”

from “Hermit of the Abdomen” Davidoff

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