Case Study 5 - Cellular Adpatations Flashcards
A 22 year old boy called Jack decides that he wants to start going to the gym.
He finds that he enjoys it but also likes the changes it makes to his appearance. He starts to go 5 times a week and starts to lift some weights. Gradually, as the weeks pass by, he notices his arms are getting bigger and he is able to lift heavier weights.
What process has caused the changes to Jack’s arms?
Hypertrophy:
physiological causes: (functional demand e.g. exercise, hormone-induced e.g. during pregnancy)
pathological causes:
(left ventricular hypertrophy)
A 22 year old boy called Jack decides that he wants to start going to the gym.
He finds that he enjoys it but also likes the changes it makes to his appearance. He starts to go 5 times a week and starts to lift some weights. Gradually, as the weeks pass by, he notices his arms are getting bigger and he is able to lift heavier weights.
What tissue type is shown in the picture. What is the difference between the 2
pictures? (1)
Image
A 22 year old boy called Jack decides that he wants to start going to the gym.
He finds that he enjoys it but also likes the changes it makes to his appearance. He starts to go 5 times a week and starts to lift some weights. Gradually, as the weeks pass by, he notices his arms are getting bigger and he is able to lift heavier weights.
What is the difference between hyperplasia and hypertrophy?
Hyperplasia is an increase in the number of cells in response to stimuli.
Hypertrophy is an increase in cell size so whole organ becomes big
A 22 year old boy called Jack decides that he wants to start going to the gym.
He finds that he enjoys it but also likes the changes it makes to his appearance. He starts to go 5 times a week and starts to lift some weights. Gradually, as the weeks pass by, he notices his arms are getting bigger and he is able to lift heavier weights.
How does hypertrophy develop at the cellular level?
Mechanical Stress:
When Jack lifts weights, he applies mechanical stress to his muscles.
Within muscle fibers, there are mechanosensors, such as integrins and other proteins, that detect this mechanical stress.
Activation of Growth Factors:
The mechanical stress activates various growth factors, including TGF-beta (Transforming Growth Factor-beta), IGF-1 (Insulin-like Growth Factor-1), and FGF (Fibroblast Growth Factor).
Vasoactive agents like angiotensin 2, endothelin 1, and thromboxane A2 may also be involved in the signaling process.
Signal Transduction Pathways:
The activated growth factors bind to their receptors, initiating signal transduction pathways.
PI3 kinase (Phosphoinositide 3-kinase) and G-protein coupled receptors are part of these pathways.
Activation of Transcription Factors:
The signal transduction pathways converge on transcription factors, such as GATA4 and MEF2 (Monocyte Enhancer 2).
These transcription factors enter the cell nucleus and activate the transcription of specific genes.
Increased Synthesis of Muscle Proteins:
The activated transcription factors stimulate the synthesis of muscle proteins, particularly myofibrillar proteins like actin and myosin.
This increased protein synthesis contributes to the growth of individual muscle fibers.
Hypertrophy:
The cumulative effect of these cellular processes is hypertrophy, where the individual muscle fibers increase in size.
This hypertrophic response is the result of an adaptation to the repeated mechanical stress imposed during resistance training.
A 22 year old boy called Jack decides that he wants to start going to the gym.
He finds that he enjoys it but also likes the changes it makes to his appearance. He starts to go 5 times a week and starts to lift some weights. Gradually, as the weeks pass by, he notices his arms are getting bigger and he is able to lift heavier weights.
Some body builders take steroids to help improve their physique. Based on what you know about steroids and how they work, can you explain
why they might want to take them?
Steroids, particularly anabolic steroids, are synthetic variations of the male sex hormone testosterone. Bodybuilders and athletes sometimes use them to enhance their physical performance and promote muscle growth. Here’s how steroids can affect the body:
Stimulation of Protein Synthesis:
Steroids work by binding to androgen receptors in cells, including muscle cells.
This binding activates the androgen receptor and stimulates the transcription of specific genes, leading to an increase in the synthesis of proteins, including muscle proteins.
This effect enhances the overall rate of protein synthesis in the body, contributing to muscle growth.
Inhibition of Corticosteroids:
Corticosteroids, which are naturally produced in the body (e.g., cortisol), have catabolic effects, meaning they promote the breakdown of complex molecules, including proteins.
Steroids can interfere with the action of corticosteroids, leading to a reduction in protein breakdown.
By inhibiting corticosteroids, steroids create an environment in which the balance between protein synthesis and degradation favors muscle growth.
Promotion of Cellular Differentiation into Hypertrophic Patterns:
Steroids can influence cellular differentiation, favoring hypertrophic patterns.
Hypertrophy involves an increase in the size of individual cells, and steroids may influence cellular processes in a way that enhances this hypertrophic response.
The exact mechanisms through which steroids affect cellular differentiation are complex and not fully understood, but it’s believed to involve interactions with various signaling pathways and gene expression.
A 22 year old boy called Jack decides that he wants to start going to the gym.
He finds that he enjoys it but also likes the changes it makes to his appearance. He starts to go 5 times a week and starts to lift some weights. Gradually, as the weeks pass by, he notices his arms are getting bigger and he is able to lift heavier weights.
Some body builders take steroids to help improve their physique.
What are the side effects associated with taking these steroids?
increased BP, enlargement of heart, infertility, hormonal imbalance, hair loss, headache
A 22 year old boy called Jack decides that he wants to start going to the gym.
He finds that he enjoys it but also likes the changes it makes to his appearance. He starts to go 5 times a week and starts to lift some weights. Gradually, as the weeks pass by, he notices his arms are getting bigger and he is able to lift heavier weights.
During pregnancy, the uterus increases in size. What cellular adaptation(s) accounts for this change?
Hypertrophy: estrogen acts on estrogen-receptor in smooth muscle lining of the uterus. This leads to an increased production of proteins which leads to an increased size of the uterus
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations. (2)
Do any of these features sound familiar?
Cushing’s syndrome which is caused by increased cortisol which may be due to use of corticosteroid medication
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations.
A urine sample is sent away for analysis. The results come back showing a raised
free cortisol level. What is cortisol and where is it secreted from?
Cortisol is indeed a steroid hormone, commonly known as the “stress hormone.” It is produced by the adrenal glands, which are located on top of each kidney. The adrenal glands have three layers, and cortisol is specifically secreted by the zona fasciculata, which is the middle layer. Cortisol plays a crucial role in various physiological functions, including metabolism regulation, immune response modulation, and helping the body cope with stress.
In times of stress or low blood glucose (hypoglycemia), the adrenal glands release cortisol into the bloodstream. This hormone helps the body mobilize energy reserves, increase blood sugar levels, and respond to stressors. It also has anti-inflammatory effects.
The symptoms described in the scenario, such as weight gain, facial hair growth (hirsutism), irregular periods, mood changes, the appearance of purple lines (known as striae or stretch marks), and the rounded face with acne-like spots, suggest a possible hormonal disorder. The elevated free cortisol level in the urine sample could be indicative of Cushing’s syndrome, a condition characterized by chronic exposure to high levels of cortisol. Cushing’s syndrome can have various causes, including the use of corticosteroid medications, adrenal tumors, or pituitary gland disorders affecting cortisol regulation.
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations.
What is the hypothalamic-pituitary-adrenal axis?
The hypothalamic-pituitary-adrenal (HPA) axis is a complex neuroendocrine system that plays a key role in the body’s response to stress and in regulating various physiological processes. It involves three main components: the hypothalamus, the pituitary gland, and the adrenal glands.
Hypothalamus:
The process begins in the hypothalamus, a region in the brain.
In response to stress, the hypothalamus releases corticotropin-releasing hormone (CRH).
Pituitary Gland:
CRH signals the pituitary gland, a small gland located at the base of the brain.
In response to CRH, the pituitary gland releases adrenocorticotropic hormone (ACTH) into the bloodstream.
Adrenal Glands:
ACTH, in turn, stimulates the adrenal glands, which are located on top of each kidney.
The adrenal glands respond to ACTH by releasing cortisol, the primary stress hormone.
Cortisol Release and Feedback Mechanism:
Cortisol has various effects on the body, including regulating metabolism, immune function, and the response to stress.
Once cortisol levels in the bloodstream reach a certain threshold, they provide negative feedback to the hypothalamus and the pituitary gland, inhibiting further release of CRH and ACTH. This feedback mechanism helps maintain cortisol levels within a normal range.
In the case described, the symptoms of weight gain, facial hair growth, irregular periods, mood changes, and the presence of purple stretch marks may be indicative of a dysfunction in the HPA axis, potentially leading to excessive cortisol production. Conditions such as Cushing’s syndrome, characterized by chronic exposure to high levels of cortisol, may be considered in the differential diagnosis.
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations.
The picture below shows a microscopic image of part of the wall of the adrenal gland. Can you label the different parts of the gland. (3)
Image
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations.
What does each layer of the adrenal gland secrete?
zona glomerulosa - mineralocorticoids (primarily aldosterone)
zona fasciculata - corticosteroids (primarily cortisol - a glucocorticoid
zona reticularis - androgens (DHEA) & sex hormones (estrogen & testosterone)
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations.
Our patient’s cortisol is elevated. Where may the problem be with the adrenal axis?
Given the symptoms described and the elevated cortisol levels, the issue with the adrenal axis may be related to the production of cortisol. The adrenal axis involves the hypothalamus, pituitary gland, and adrenal glands, and dysfunction at any of these levels can lead to abnormal cortisol production. Let’s explore the potential causes:
Adrenal Tumor (Benign):
An adrenal tumor, particularly an adenoma (benign tumor) in the adrenal cortex, can lead to overproduction of cortisol.
This excess cortisol production is not under the normal regulatory control, leading to elevated levels of cortisol in the blood.
Pituitary Gland Dysfunction:
The pituitary gland produces adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol.
If there is a tumor or dysfunction in the pituitary gland, it may result in excessive production of ACTH, leading to increased cortisol secretion from the adrenal glands.
Hypothalamic Dysfunction:
The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release ACTH.
Dysfunction in the hypothalamus may result in increased CRH production, leading to elevated levels of ACTH and cortisol.
Steroid Medication:
Prolonged use of exogenous steroids (corticosteroid medications) can also lead to elevated cortisol levels.
This is because these medications can suppress the normal feedback mechanisms in the HPA (hypothalamic-pituitary-adrenal) axis, leading to increased cortisol production.
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations.
What is this condition called?
Cushing’s syndrome
A 39 year old lady has been gaining a lot of weight. There has been no change to her diet and she has always been very conscious of what she eats. She has noticed that she has been having a lot of hair growth on her face which has become embarrassing for her. Her periods have become irregular and she has
noticed she loses her patience very quickly. Purple lines have appeared across
her abdomen. She goes to
see her GP who notices a
striking change in her
appearance compared to
when he saw her previously. She notices a
much more rounded face,
and lots of spots on her
face. She also shows her
the ‘stretch marks’ on her
abdomen. The GP is
concerned and orders
some investigations.
If we examined the patient’s adrenal glands under the microscope, what cellular adaptation do you think we would observe?
Bilateral cortical hyperplasia which is in response to continuous production of ACTH. This leads to an increased size of adrenal glands
