ZR + Adrenal Medulla (For Quiz)

*Question: Which hormones are primarily produced by the zona reticularis of the adrenal cortex?

A) Cortisol and corticosterone
B) Aldosterone and cortisol
C) Androstenedione and DHEA
D) Epinephrine and norepinephrine

*Answer: C) Androstenedione and DHEA

*Question: What is the storage form of DHEA that serves as a backup stock in the body?

A) Androstenedione
B) DHEA sulfate (DHEA-S)
C) Testosterone
D) Dihydrotestosterone

*Answer: B) DHEA sulfate (DHEA-S)

*Question: In females, what is the main source of sex drive (libido)?

A) Estrogen from the ovaries
B) Progesterone
C) Androgens from the adrenal cortex
D) Testosterone from the ovaries

*Answer: C) Androgens from the adrenal cortex

*Question: Which hormone can androgens be converted to in peripheral tissues of males?

A) Estradiol only
B) Cortisol
C) Aldosterone
D) Testosterone and dihydrotestosterone

*Answer: D) Testosterone and dihydrotestosterone

*Question: What condition can occur in males with adrenal androgen excess due to suppression of GnRH, FSH, and LH?

A) Hypertension
B) Infertility and hypogonadal symptoms
C) Cushing's syndrome
D) Addison's disease

*Answer: B) Infertility and hypogonadal symptoms

*Question: Which of the following is a masculinizing effect seen in females with adrenal androgen excess?

A) Increased breast tissue
B) Hirsutism
C) Increased estrogen levels
D) Enhanced fertility

*Answer: B) Hirsutism

*Question: What is virilization in females with androgen excess?

A) Development of female secondary sex characteristics
B) Development of masculine physical appearance
C) Increased ovulation
D) Enhanced menstrual regularity

*Answer: B) Development of masculine physical appearance

*Question: What percentage of Congenital Adrenal Hyperplasia (CAH) cases are caused by 21-hydroxylase deficiency?

A) 50-60%
B) 70-80%
C) 90-95%
D) 100%

*Answer: C) 90-95%

*Question: In 21-hydroxylase deficiency, which hormones are decreased?

A) ACTH and androgens
B) Cortisol and aldosterone
C) Epinephrine and norepinephrine
D) DHEA and testosterone

*Answer: B) Cortisol and aldosterone

*Question: In CAH due to 21-hydroxylase deficiency, why are adrenal androgens produced in excess?

A) Direct stimulation by ACTH
B) All accumulated substrates are diverted to the androgen pathway in zona reticularis
C) Increased enzyme activity in zona glomerulosa
D) Decreased breakdown of androgens

*Answer: B) All accumulated substrates are diverted to the androgen pathway in zona reticularis

*Question: What causes adrenal hyperplasia in CAH?

A) High cortisol levels
B) Chronic ACTH stimulation due to low cortisol
C) Excess aldosterone production
D) Decreased androgen levels

*Answer: B) Chronic ACTH stimulation due to low cortisol

*Question: Which physical finding in a newborn female with CAH may lead to incorrect sex assignment at birth?

A) Small clitoris
B) Clitoromegaly and labial fusion
C) Absence of ovaries
D) Enlarged adrenal glands

*Answer: B) Clitoromegaly and labial fusion

*Question: Why is early newborn screening for CAH important?

A) To prevent respiratory distress
B) To prevent incorrect sex assignment and allow early treatment
C) To identify potential kidney problems
D) To assess thyroid function

*Answer: B) To prevent incorrect sex assignment and allow early treatment

*Question: What is the primary treatment approach for CAH to reduce androgen excess?

A) Androgen receptor blockers
B) Cortisol replacement to suppress ACTH
C) Aldosterone antagonists
D) Estrogen therapy

*Answer: B) Cortisol replacement to suppress ACTH

*Question: Among newborn screening endocrine disorders, which one may require surgical correction?

A) Hypothyroidism
B) PKU
C) CAH
D) Galactosemia

*Answer: C) CAH

*Question: What type of cells are found in the adrenal medulla?

A) Corticotrope cells
B) Chromaffin cells
C) Beta cells
D) Alpha cells

*Answer: B) Chromaffin cells

*Question: Which amino acid is the precursor for both catecholamines and thyroid hormones?

A) Tryptophan
B) Phenylalanine
C) Tyrosine
D) Histidine

*Answer: C) Tyrosine

*Question: Which catecholamine is the principal product of the adrenal medulla and is made only in the medulla?

A) Dopamine
B) Norepinephrine
C) Epinephrine
D) DOPA

*Answer: C) Epinephrine

*Question: Where can norepinephrine be synthesized and stored?

A) Only in the adrenal medulla
B) In the adrenal medulla and peripheral sympathetic nerves
C) Only in peripheral sympathetic nerves
D) In the adrenal cortex

*Answer: B) In the adrenal medulla and peripheral sympathetic nerves

*Question: In what medical emergency is epinephrine commonly used to temporarily restart or stimulate the heart?

A) Diabetic ketoacidosis
B) Cardiac arrest
C) Hyperthyroidism
D) Adrenal crisis

*Answer: B) Cardiac arrest

*Question: What is the correct sequence in catecholamine biosynthesis?

A) Tyrosine → Dopamine → L-Dopa → Norepinephrine → Epinephrine
B) Tyrosine → L-Dopa → Dopamine → Norepinephrine → Epinephrine
C) L-Dopa → Tyrosine → Dopamine → Epinephrine → Norepinephrine
D) Dopamine → Tyrosine → L-Dopa → Norepinephrine → Epinephrine

*Answer: B) Tyrosine → L-Dopa → Dopamine → Norepinephrine → Epinephrine

*Question: Where does the conversion of dopamine to norepinephrine occur in chromaffin cells?

A) In the cytoplasm
B) In the nucleus
C) In the mitochondria
D) In the endoplasmic reticulum

*Answer: B) In the nucleus

*Question: What is the relationship between norepinephrine and epinephrine synthesis?

A) They are produced independently
B) Epinephrine is synthesized from norepinephrine
C) Norepinephrine is synthesized from epinephrine
D) They both come directly from dopamine

*Answer: B) Epinephrine is synthesized from norepinephrine

*Question: What is the effect of binding to Alpha₁ adrenergic receptors?

A) Bronchial smooth muscle relaxation
B) Vascular smooth muscle contraction and vasoconstriction
C) Decreased heart rate
D) Lipolysis and energy expenditure

*Answer: B) Vascular smooth muscle contraction and vasoconstriction

*Question: What is the function of Alpha₂ adrenergic receptors?

A) Increase heart rate
B) Suppress/inhibit release of norepinephrine (negative feedback)
C) Increase blood pressure
D) Stimulate lipolysis

*Answer: B) Suppress/inhibit release of norepinephrine (negative feedback)

*Question: Which adrenergic receptor is responsible for cardiac effects such as increased heart rate and contractility?

A) Alpha₁
B) Alpha₂
C) Beta₁
D) Beta₂

*Answer: C) Beta₁

*Question: What is the effect of Beta₂ receptor activation?

A) Cardiac muscle contraction
B) Vascular smooth muscle contraction
C) Bronchial, vascular, and uterine smooth muscle relaxation
D) Suppression of catecholamine release

*Answer: C) Bronchial, vascular, and uterine smooth muscle relaxation

*Question: Which adrenergic receptor is responsible for energy expenditure and lipolysis?

A) Alpha₁
B) Beta₁
C) Beta₂
D) Beta₃

*Answer: D) Beta₃

*Question: What is the primary purpose of the fight-or-flight response?

A) To promote digestion
B) To respond to severe external threat and survive
C) To decrease metabolic rate
D) To promote sleep

*Answer: B) To respond to severe external threat and survive

*Question: Which division of the autonomic nervous system is activated during the fight-or-flight response?

A) Parasympathetic nervous system
B) Enteric nervous system
C) Sympathetic nervous system
D) Somatic nervous system

*Answer: C) Sympathetic nervous system

*Question: During fight-or-flight response, why does sphincter tone of bowel and bladder increase?

A) To promote elimination
B) To slow down digestion and urination so blood can be redirected to muscles and brain
C) To increase water reabsorption
D) To enhance nutrient absorption

*Answer: B) To slow down digestion and urination so blood can be redirected to muscles and brain

*Question: What happens during extremely high anxiety that may cause loss of bladder or bowel control?

A) Complete shutdown of the sympathetic system
B) The sympathetic system overflows to the parasympathetic system
C) Increased Beta₁ receptor activation
D) Decreased catecholamine production

*Answer: B) The sympathetic system overflows to the parasympathetic system

*Question: What is the half-life of epinephrine and norepinephrine?

A) 30 seconds
B) Approximately 2 minutes
C) 10 minutes
D) 1 hour

*Answer: B) Approximately 2 minutes

*Question: Which hormone takes over during prolonged stress when catecholamines cannot sustain long-term stress?

A) Aldosterone
B) Thyroid hormone
C) Cortisol
D) Growth hormone

*Answer: C) Cortisol

*Question: What effect does norepinephrine have on blood vessels during stress?

A) Widespread vasodilation
B) Selective vasodilation in muscles only
C) Widespread vasoconstriction resulting in increased blood pressure
D) No effect on blood vessels

*Answer: C) Widespread vasoconstriction resulting in increased blood pressure

*Question: Why does epinephrine cause dilation of bronchioles during stress?

A) To decrease oxygen intake
B) To assist in pulmonary ventilation and increase oxygen supply
C) To decrease metabolic rate
D) To promote rest and digestion

*Answer: B) To assist in pulmonary ventilation and increase oxygen supply

*Question: What percentage of catecholamines are taken up locally by nerve endings (Uptake 1)?

A) 50%
B) 70%
C) 90%
D) 100%

*Answer: C) 90%

*Question: Which enzymes are responsible for degradation of catecholamines in non-neuronal tissues (Uptake 2)?

A) Lipase and amylase
B) COMT and MAO
C) StAR and desmolase
D) 21-hydroxylase and 11-β-hydroxylase

*Answer: B) COMT and MAO

*Question: What does COMT (catechol-O-methyltransferase) convert epinephrine to?

A) Normetanephrine
B) Metanephrine
C) VMA
D) HVA

*Answer: B) Metanephrine

*Question: What does COMT convert norepinephrine to?

A) Metanephrine
B) Epinephrine
C) Normetanephrine
D) Dopamine

*Answer: C) Normetanephrine

*Question: What is the final metabolite of epinephrine and norepinephrine that is excreted in urine?

A) Metanephrine
B) Normetanephrine
C) Homovanillic acid (HVA)
D) Vanillylmandelic acid (VMA)

*Answer: D) Vanillylmandelic acid (VMA)

*Question: Which enzyme converts metanephrine and normetanephrine to VMA?

A) COMT
B) MAO (Monoamine Oxidase)
C) Tyrosine hydroxylase
D) DOPA decarboxylase

*Answer: B) MAO (Monoamine Oxidase)

*Question: What is the final breakdown product of dopamine that is excreted in urine?

A) VMA
B) Metanephrine
C) Homovanillic acid (HVA)
D) Normetanephrine

*Answer: C) Homovanillic acid (HVA)

*Question: What is pheochromocytoma?

A) Tumor of the adrenal cortex producing excess cortisol
B) Rare catecholamine-producing tumor of chromaffin cells causing episodic hypertension
C) Benign tumor of the pituitary gland
D) Tumor of the thyroid gland

*Answer: B) Rare catecholamine-producing tumor of chromaffin cells causing episodic hypertension

*Question: What is the classic triad of symptoms in pheochromocytoma?

A) Hypertension, hyperglycemia, and hypokalemia
B) Profuse sweating, palpitations, and headache
C) Weight gain, moon face, and purple striae
D) Hirsutism, acne, and virilization

*Answer: B) Profuse sweating, palpitations, and headache

*Question: Why does pheochromocytoma cause episodic (paroxysmal) hypertension rather than continuous hypertension?

A) The tumor produces hormones intermittently
B) Catecholamines have a short half-life (~1-2 minutes)
C) The patient's receptors become desensitized
D) Blood volume fluctuates rapidly

*Answer: B) Catecholamines have a short half-life (~1-2 minutes)

*Question: What is the best screening test for pheochromocytoma?

A) Plasma cortisol level
B) Urinary VMA only
C) Metanephrine level
D) ACTH stimulation test

*Answer: C) Metanephrine level

*Question: Why is metanephrine a better screening marker than VMA for pheochromocytoma?

A) VMA is not excreted in urine
B) The tumor converts catecholamines to metanephrines within chromaffin cells before release
C) Metanephrine has a longer half-life in blood
D) VMA is only produced in healthy tissue

*Answer: B) The tumor converts catecholamines to metanephrines within chromaffin cells before release

*Question: What specimen preparation is required for plasma catecholamine collection in suspected pheochromocytoma?

A) Random collection any time of day
B) Overnight fast, patient in reclining position in quiet environment for 20-30 min, pre-chilled EDTA tube
C) Post-exercise collection
D) Standing position for 1 hour before collection

*Answer: B) Overnight fast, patient in reclining position in quiet environment for 20-30 min, pre-chilled EDTA tube

*Question: Why must the patient fast overnight before plasma catecholamine collection?

A) To increase catecholamine levels
B) To avoid interference by catecholamine-rich foods like coffee and bananas
C) To decrease cortisol levels
D) To enhance ACTH production

*Answer: B) To avoid interference by catecholamine-rich foods like coffee and bananas

*Question: What is the confirmatory test for locating a pheochromocytoma tumor?

A) ACTH stimulation test
B) Dexamethasone suppression test
C) CT or MRI imaging of adrenal glands
D) Overnight metyrapone test

*Answer: C) CT or MRI imaging of adrenal glands

*Question: What is the principle of the clonidine suppression test in pheochromocytoma diagnosis?

A) Clonidine increases catecholamine release from tumors
B) Clonidine suppresses catecholamine release from nervous system but has no effect on tumor release
C) Clonidine stimulates ACTH production
D) Clonidine inhibits cortisol synthesis

*Answer: B) Clonidine suppresses catecholamine release from nervous system but has no effect on tumor release

*Question: In a normal patient, what happens to catecholamine levels after clonidine administration?

A) Catecholamines increase
B) Catecholamines remain unchanged
C) Catecholamines decrease
D) Catecholamines convert to metanephrines

*Answer: C) Catecholamines decrease

*Question: In a patient with pheochromocytoma, what happens to catecholamine levels after clonidine administration?

A) Catecholamines decrease significantly
B) Catecholamines remain elevated (no suppression)
C) Catecholamines convert to inactive forms
D) Catecholamines increase further

*Answer: B) Catecholamines remain elevated (no suppression)

*Question: What is the principle of the glucagon stimulation test for pheochromocytoma?

A) Glucagon stimulates cortisol production
B) In normal patients, glucagon raises glucose and catecholamines are suppressed; in pheochromocytoma, catecholamines remain elevated
C) Glucagon directly stimulates tumor growth
D) Glucagon decreases blood pressure

*Answer: B) In normal patients, glucagon raises glucose and catecholamines are suppressed; in pheochromocytoma, catecholamines remain elevated

*Question: What is paraganglioma?

A) Tumor of chromaffin cells in the adrenal medulla
B) Tumor of chromaffin cells outside the adrenal medulla
C) Tumor of the adrenal cortex
D) Benign tumor of the pituitary gland

*Answer: B) Tumor of chromaffin cells outside the adrenal medulla

*Question: Where can paragangliomas be located?

A) Only in the adrenal glands
B) Only in the brain
C) Abdomen, sympathetic ganglia, and other extra-adrenal sites
D) Only in the thyroid gland

*Answer: C) Abdomen, sympathetic ganglia, and other extra-adrenal sites

*Question: Which of the following stimuli commonly triggers catecholamine release?

A) Low metabolic rate
B) Hypoxemia, hypothermia, hypoglycemia, and hypovolemia
C) High calcium levels
D) Decreased heart rate

*Answer: B) Hypoxemia, hypothermia, hypoglycemia, and hypovolemia

*Question: Why does the body release catecholamines during hypoglycemia?

A) To decrease glucose levels
B) To increase glucose production for brain alertness, muscle activity, and decision-making
C) To promote insulin secretion
D) To inhibit gluconeogenesis

*Answer: B) To increase glucose production for brain alertness, muscle activity, and decision-making

*Question: What type of stress can trigger catecholamine release?

A) Only physical stress
B) Only physiological stress
C) Physiological stress, physical activity, and psychological stress
D) Only psychological stress

*Answer: C) Physiological stress, physical activity, and psychological stress

*Question: How do catecholamines differ from cortisol in stress response?

A) Catecholamines are slow-acting and long-term; cortisol is immediate
B) Catecholamines are immediate and short-lived; cortisol is slower onset and long-term
C) Both have the same duration of action
D) Catecholamines suppress the immune system; cortisol does not

*Answer: B) Catecholamines are immediate and short-lived; cortisol is slower onset and long-term

*Question: During what type of emergency might someone experience "superhuman strength" due to catecholamines?

A) Chronic stress
B) Immediate emergencies like lifting heavy objects during panic
C) Long-term illness
D) Sleep deprivation

*Answer: B) Immediate emergencies like lifting heavy objects during panic

*Question: What effect does prolonged cortisol elevation have on the immune system?

A) Enhances immune function
B) No effect on immunity
C) Suppresses the immune system over time
D) Only affects the adaptive immune system

*Answer: C) Suppresses the immune system over time

*Question: In catecholamine metabolism, what does Uptake 1 refer to?

A) Degradation by COMT in the liver
B) 90% of catecholamines taken up locally by nerve endings
C) Conversion to VMA in peripheral tissues
D) Excretion through the kidneys

*Answer: B) 90% of catecholamines taken up locally by nerve endings

*Question: Where does COMT primarily act to degrade catecholamines?

A) In nerve endings only
B) In the adrenal medulla, liver, and other non-neuronal tissues
C) Only in the brain
D) In the kidneys only

*Answer: B) In the adrenal medulla, liver, and other non-neuronal tissues

*Question: What functional role do Alpha₂ receptors play in catecholamine signaling?

A) Amplify the stress response
B) Act as negative feedback to limit catecholamine release
C) Increase vasoconstriction
D) Stimulate cardiac contractility

*Answer: B) Act as negative feedback to limit catecholamine release

*Question: Why are catecholamine effects short-lived?

A) They are rapidly metabolized by the liver only
B) Alpha₂ receptors provide negative feedback, causing quick rise and quick fall
C) They bind irreversibly to receptors
D) The adrenal medulla stops producing them after release

*Answer: B) Alpha₂ receptors provide negative feedback, causing quick rise and quick fall

*Question: What cardiovascular effect occurs when Beta₁ receptors are activated?

A) Decreased heart rate and contractility
B) Increased heart rate and contractility to pump more blood during stress
C) Vasodilation of peripheral vessels
D) Decreased blood pressure

*Answer: B) Increased heart rate and contractility to pump more blood during stress

*Question: What is the purpose of bronchodilation caused by Beta₂ receptor activation during stress?

A) To decrease oxygen intake
B) To increase oxygen intake and supply during fight-or-flight
C) To reduce heart rate
D) To promote relaxation

*Answer: B) To increase oxygen intake and supply during fight-or-flight

*Question: What metabolic effect occurs with Beta₃ receptor activation?

A) Decreased energy production
B) Stimulation of glucose production and increased energy supply for stress response
C) Inhibition of lipolysis
D) Decreased metabolic rate

*Answer: B) Stimulation of glucose production and increased energy supply for stress response

*Question: During fight-or-flight response, why do pupils dilate?

A) To decrease light sensitivity
B) To improve eyesight and see surroundings clearly
C) To conserve energy
D) To reduce visual stimuli

*Answer: B) To improve eyesight and see surroundings clearly

*Question: What is piloerection and when does it occur?

A) Decreased hair growth during stress
B) Hair standing up (goosebumps) during fight-or-flight response
C) Hair loss during chronic stress
D) Increased hair pigmentation

*Answer: B) Hair standing up (goosebumps) during fight-or-flight response

*Question: Why does the body mobilize fuel stores during the fight-or-flight response?

A) To store more energy for later use
B) To provide quick energy through gluconeogenesis to respond to stressors
C) To decrease metabolic rate
D) To promote fat storage

*Answer: B) To provide quick energy through gluconeogenesis to respond to stressors

*Question: What happens to gastrointestinal secretion and motor activity during fight-or-flight?

A) They are enhanced to provide energy
B) They remain unchanged
C) They are inhibited so the body can focus resources on survival
D) They increase to improve digestion

*Answer: C) They are inhibited so the body can focus resources on survival

*Question: What is the purpose of increased metabolic rate during catecholamine release?

A) To conserve energy
B) To increase oxygen consumption, heat production, and energy availability throughout the body
C) To decrease body temperature
D) To promote sleep

*Answer: B) To increase oxygen consumption, heat production, and energy availability throughout the body

*Question: In CAH, which zones of the adrenal cortex are underfunctioning?

A) Zona reticularis only
B) Zona fasciculata and zona glomerulosa
C) Zona reticularis and zona glomerulosa
D) All three zones equally

*Answer: B) Zona fasciculata and zona glomerulosa

*Question: In CAH, which zone becomes hyperactive due to substrate diversion?

A) Zona glomerulosa
B) Zona fasciculata
C) Zona reticularis
D) Adrenal medulla

*Answer: C) Zona reticularis

*Question: What is the consequence of treating CAH early with cortisol replacement?

A) It increases androgen production
B) It suppresses ACTH and reduces androgen excess
C) It stimulates adrenal hyperplasia
D) It decreases blood pressure

*Answer: B) It suppresses ACTH and reduces androgen excess

*Question: In females with adrenal androgen excess, what causes follicle arrest and anovulation?

A) Increased estrogen levels
B) Suppression of normal estrogen production leading to no development of follicles
C) Excess progesterone
D) High aldosterone levels

*Answer: B) Suppression of normal estrogen production leading to no development of follicles

*Question: What effect does high androgen level have on hair follicles, potentially causing male pattern baldness?

A) Stimulation of hair growth
B) Shrinkage of hair follicles
C) Increased hair pigmentation
D) No effect on hair follicles

*Answer: B) Shrinkage of hair follicles

*Question: In males with adrenal androgen excess, why might the testes decrease in size?

A) Direct toxic effect of androgens
B) Suppression of GnRH, FSH, and LH leading to reduced testicular function
C) Increased testosterone production by testes
D) Enhanced spermatogenesis

*Answer: B) Suppression of GnRH, FSH, and LH leading to reduced testicular function

*Question: What is the problem when adrenal glands produce excess androgens that convert to testosterone in males?

A) It enhances fertility
B) Adrenal testosterone cannot sustain normal male reproductive function, leading to infertility
C) It increases testicular size
D) It promotes normal spermatogenesis

*Answer: B) Adrenal testosterone cannot sustain normal male reproductive function, leading to infertility

*Question: Why is androgen excess more severe and noticeable in females than males?

A) Females have more androgen receptors
B) Normally, androgens should never increase significantly in women
C) Males metabolize androgens faster
D) Females cannot convert androgens to other hormones

*Answer: B) Normally, androgens should never increase significantly in women

*Question: What precursor accumulates when 21-hydroxylase is deficient in CAH?

A) Cortisol
B) Aldosterone
C) 17-OH progesterone
D) Metanephrine

*Answer: C) 17-OH progesterone

*Question: In 21-hydroxylase deficiency, why can't progesterone be converted to 11-deoxycorticosterone?

A) The enzyme is absent in zona glomerulosa
B) There is too much aldosterone
C) ACTH is too low
D) The patient is taking medication that blocks conversion

*Answer: A) The enzyme is absent in zona glomerulosa

*Question: Among NBS endocrine disorders, why might CAH specifically require surgery?

A) To remove hyperplastic adrenal tissue
B) To correct clitoromegaly causing virilized genitalia
C) To repair kidney damage
D) To correct hypothyroidism

*Answer: B) To correct clitoromegaly causing virilized genitalia

*Question: What psychological impact can occur if CAH is detected late in a child's development?

A) Enhanced cognitive function
B) Severe psychological distress from incorrect sex assignment
C) Improved social adaptation
D) No psychological impact

*Answer: B) Severe psychological distress from incorrect sex assignment

*Question: Besides cortisol replacement, what other hormone replacement may be needed in CAH treatment?

A) Thyroid hormone
B) Growth hormone
C) Mineralocorticoid (aldosterone) replacement
D) Insulin

*Answer: C) Mineralocorticoid (aldosterone) replacement

*Question: What analytical method is recommended for measuring 24-hour urine cortisol in Cushing's syndrome evaluation?

A) Radioimmunoassay
B) ELISA
C) Tandem Mass Spectrometry
D) Spectrophotometry

*Answer: C) Tandem Mass Spectrometry

*Question: What is the main limitation of 24-hour urine cortisol collection?

A) It is too sensitive
B) It is very impractical for many patients to perform correctly
C) It cannot detect free cortisol
D) It requires hospitalization

*Answer: B) It is very impractical for many patients to perform correctl