study guide part 2

Question 1

Discuss predominant cell types and their function in the innate immune system.

Answer 1

> phagocytes (eg. neutrophils - arrive 6-24 hrs post-infection/injury and are most abundant) or (eg. macrophages - arrive 24-48 hrs post-injury/infection and may be free like alveolar macrophages or fixed like microglia) - ingest bacteria/foreign particles/dead cell matter

> natural killer cells - attack cells that don’t show the MHC protein which identify it as “self” on their surface membranes. They induce apoptosis in cancer and virus-infected cells. Secrete chemicals like interferons that enhance inflam response. Releases perforin leading to osmotic cell lysis

> eosinophils - play a role in allergic reaction and control helminthes

> monocytes - migrate into tissues to become macrophages

> basophils - release histamines and heparin

> mast cells - release histamines

Question 2

Describe the different types of pain experienced by the body and their cause.

Answer 2

Acute:
>rapid onset, well localised, responds well to analgesics

Chronic:
>slowly developing continuous or recurring pain, difficult to treat, is a “learned” response involving glutamate and NMDA receptors. May be associated with hyperanalgesia (increased sensitivity to noxious stimuli), does not respond well to opioid drugs

Referred:
>pain from one body region perceived from a different region
>visceral and somatic pain fibers travel in the same nerves so the brain assumes stimulus from common (somatic) region
>eg. Someone with gallbladder pain may feel pain in the shoulder
>eg. Left-arm or jaw pain could be angina

Visceral:
>Felt as vague aching, gnawing, burning
>Activated by tissue stretching, ischemia, chemicals, muscle spasms

Question 3

Describe the pathophysiology of motor neurone disease

Answer 3

A rare form of neurodegeneration associated with the degeneration of upper and lower motor neurones which can lead to muscle wasting and paralysis.

> muscle wasting which begins as weakness and progresses to fatal paralysis is caused by the degeneration of the axons of affected nerves.

Question 4

Outline the common pathophysiological

processes implicated in neuro-degeneration

Answer 4

Common processes include:
>oxidative stress
>intracellular protein aggregation
>mitochondrial dysfunction

Other mechanisms, which may also play a role, include >neuroinflammation
>excitotoxicity
>apoptosis.

Question 5

Describe the pathophysiology of Parkinson’s disease

Answer 5

A neurodegenerative disorder associated with the loss of dopamine secreting neurones - decreased dopamine causes alterations in muscle function.

Clinical manifestations:
T - tremor at rest
R - rigidity (puts them at increased risk of falls)
A - akinesia (absence of movement) or bradykinesia (slow movement)
P - postural instability

Question 6

Describe the pathophysiology of Huntington’s disease

Answer 6

An autosomal dominant genetic disorder/neurodegenerative disorder (if you have a parent with it, you have a 50% change of developing it) involving a mutation resulting in the formation of a protein called Huntington

The protein miss-folding leads to its aggregation in the cells of the brain leading to neuronal cell loss in the basal ganglia and cerebral cortex - so you can actually see big holes in the brain - causing a decrease in the activity of the inhibitory neurotransmitter GABA.

Question 7

Describe the pathophysiology of multiple sclerosis.

Answer 7

A chronic autoimmune inflammatory disease where the immune cells (B and T cells) destroy the CNS myelin leading to plaque formation and causing impairments in motor, sensory, and neurological function.

Patients may experience:
>extreme fatigue 
>memory loss
>depression
>visual disturbances
>loss of coordination
>tremor

Question 8

Describe the pathophysiology of spinal cord injury

Answer 8

The pathophysiology of SCI consists of a primary and secondary phase of injury.
>In the primary phase, the injury to the spine directly exerts a force to the spinal cord disrupting axons, blood vessels, and cell membranes. Neurological deficits are present immediately.
>The secondary phase leads to tissue destruction and involves inflammation, oedema, vascular dysfunction, ischaemia, excitotoxicity, and delayed apoptotic cell death.

> CNS neurons do not repair. PNS neurons are capable of repair but only if the injury is near the distal end of the axon.

In a complete injury, the entire spinal cord has been severed, all function below the area of injury is lost.

In an incomplete injury, you only lose some function below the site of trauma.

Question 9

Describe the pathophysiology of incomplete spinal cord syndrome.

Answer 9

Central spinal cord syndrome- inverse paraplegia.
>ie. the legs function but the hands and arms are paralysed
>Associated with ischaemia and haemorrhage that damages the corticospinal fibres that control the arms

Anterior cord syndrome - associated with flexion injuries to the cervical spine.

Motor function, pain and temperature are all lost below the site, however, touch, proprioception and vibrational sensations are maintained

Posterior cord syndrome - is very rare.

Results in a loss of proprioception below the level on injury

Motor and pain/sensitivity to light touch remain intact

Brown-sequard syndrome - occurs when the spinal cord is injured on the lateral side (more common) or is hemisectioned (rare)

Usually occurs due to some kind of penetrating wound and leads to loss of motor function on the same side of the injury and loss of sensation on the opposite side of the spinal cord

Question 10

Describe the pathophysiology of traumatic brain injury

Answer 10

An impact, penetration, or rapid movement of the brain within the skull that results in an altered mental state/damage.

May be classified as either:
1. Closed head trauma (blunt) - most common
>eg. Punching someone in the head
2. Penetrating head trauma (open)
>eg. Stabbing someone in the skull with a knife

Question 11

Compare and contrast the pathophysiology observed in an ischaemic stroke versus a haemorrhagic stroke.

Answer 11

Ischaemic (thrombotic or emboli)
>when there is an area of the brain deprived of blood.
>thrombotic - caused by a blood clot blocking the flow of blood to the brain
>emboli - occurs when fatty plaque or a blood clot breaks away and flows to the brain where it blocks an artery.

Haemorrhagic - occurs when a break in the blood vessel (an aneurysm) causes bleeding in the brain.

The patient may have problems with their motor, speech, sensory, language and cognitive functions

Question 12

Describe the main homeostatic imbalances and diseases of the endocrine glands studies this
semester.

Answer 12

> elevated hormones
depressed hormones

Alterations in pituitary function:
>Syndrome of inappropriate antidiuretic hormone
>Diabetes insipidus (low ADH production)
>Acromegaly
>gigantism
>dwarfism

Alterations in thyroid function:
>hyperthyroiditis
>hypothyroidism
>Hashimoto's disease
>grave's disease
>thyroid storm

Alterations in parathyroid function:
>hyperparathyroidism
>hyperparathyroidism

Alterations in pancreatic function:
>diabetes type 1 & 2
>gestational diabetes

Alterations in adrenal function:
>hypoaldosteronism
>hyperaldosteronism
>hypercortisolism 
>cushing syndrome

Question 13

Discuss the pathophysiology, signs/symptoms, and tests that may be used to diagnose Grave’s disease

Answer 13

An autoimmune disease characterised by an overactive thyroid (thyroid starts making lots of T3 and T4) due to thyroid-stimulating immunoglobulins binding to the thyroid cells, stimulating the production of too much thyroid hormone, secretion and goitre formation.

Causes hyperthyroiditis.

S&S:
>psychiatric problems 
>rhythm irregularities of the heart
>graves ophthalmology (bugged out eyes)
>overactive metabolism which can lead to rapid weight loss

Tests:
>blood tests - determine the amount of TSH (usually lower in people with Grave’s) and thyroid hormone (usually higher)
>ultrasound - can determine if the thyroid is enlarged
>Radioactive iodine uptake - your doctor can determine the rate at which your thyroid gland takes up iodine. The amount helps determine if Graves’ disease or another condition is the cause of the hyperthyroidism.

Question 14

Discuss the pathophysiology, signs/symptoms, and tests that may be used to diagnose Hashimoto’s thyroiditis.

Answer 14

An autoimmune disease where the thyroid gland is identified as non-self and is attacked by a variety of cell and antibody medicated immune processes, damaging the thyroid and decreasing thyroid hormone production. This may initially lead to hyperthyroidism before we see an enlarged and inflamed hypo functioning thyroid called a goitre.

S&S:
>myxoedematous psychosis
>weight gain
>mania
>sensitivity to cold and heat
>fatigue 
>hair loss
>memory loss
>depression

Tests:
>Blood tests - if your thyroid is underactive, the level of thyroid hormone is low. The level of TSH is elevated because your pituitary gland tries to stimulate your thyroid gland to produce more thyroid hormone.
>An antibody test - may confirm the presence of antibodies against thyroid peroxidase (TPO antibodies), an enzyme normally found in the thyroid gland that plays an important role in the production of thyroid hormones.

Question 15

Discuss the pathophysiology, signs/symptoms, and tests that may be used to diagnose Diabetes Mellitus type 1 and 2.

Answer 15

A collection of disorders characterised by glucose intolerance, chronic hyperglycaemia and alterations in protein, fat and carb metabolism.
>ie. because the body isn’t able to get energy from glucose, the body starts to use fats as fuel and ten protein.

> type 1 is an autoimmune disease when we see the destruction of pancreatic beta cells. As a result, they produce insufficient amounts of insulin. Polyuria and polydipsia are common.

> type 2 diabetes is related to diet and lifestyle. Insulin is produced but either not in sufficient quantities or the insulin receptors on the cell’s surface become blind to insulin.

S&S:
>polyuria
>polydipsia

Tests:
>Glycated hemoglobin (A1C) test - indicates your average blood sugar level for the past two to three months.
>Random blood sugar test - a blood sugar level of 11.1 mmol/L or higher suggests diabetes.
>Fasting blood sugar test - a fasting blood sugar level 5.6 to 6.9 mmol/L is considered prediabetes. If its 7 mmol/L+ on two separate tests, you have diabetes.
>urinalysis - ketones in the urine suggest diabetes type 1. Glucosuria is a sign of both types 1 and 2.

Question 16

Discuss the pathophysiology, signs/symptoms, and tests that may be used to diagnose Cushing’s syndrome.

Answer 16

Excessive secretion of adrenocorticotropin hormone (ACTH) by a pituitary tumour.
>The most common cause of Cushing’s syndrome is
exogenous administration of glucocorticoids (for asthma, immunosuppression etc.).
>Pituitary Cushing’s occurs when a benign pituitary adenoma secretes ACTH.
>Adrenal Cushing’s occurs when excess cortisol is produced by adrenal gland tumours, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.

S&S:
>Because cortisol is a stress hormone, patients may find themselves feeling stressed and anxious.
C - central obesity, cervical fat pads (buffalo hump), collagen fibre weakness, comedones (acne)
U - urinary free cortisol and glucose increase
S - stiae, suppressed immunity
H - hypercorticolism, hypertension, hyperglycaemia, hyper cholesterolemia, hirsutism (increased facial hair in women), hypernatremia, hypokalemia
I - iatrogenic (caused by administration of corticosteroids)
N - noniatrogenic (neoplasms - some kind of growth)
G - glucose intolerance, growth retardation

Tests:
>Urine and blood tests - measure hormone levels in your urine and blood and show whether your body is producing excessive cortisol.
>Saliva test - by analyzing cortisol levels from a small sample of saliva collected late at night, doctors can see if cortisol levels are too high, suggesting a diagnosis of Cushing syndrome.
>Imaging tests - CT or MRI scans can provide images of your pituitary and adrenal glands to detect abnormalities, such as tumors.
>Petrosal sinus sampling - can help determine whether the cause of endogenous Cushing syndrome is rooted in the pituitary or somewhere else.

Question 17

Discuss the pathophysiology, signs/symptoms, and tests that may be used to diagnose Addison’s disease.

Answer 17

Results from the destruction of the adrenal cortex, which leads to deficiencies in glucocorticoids, and mineralocorticoids. Usually presents with glucocorticoid deficiency followed by mineralocorticoid. Destruction may be caused by adrenal insufficiency, secondary adrenal insufficiency caused by ACTH deficiency e.g. removal of the pituitary, tuberculosis which can
destroy the adrenal glands, cancer and chronic fungal infection.

S&S:
>chronic fatigue
>muscle weakness
>weight loss
>loss of appetite 
>N&V, fainting 
>low BP

Tests:
>Blood test - can measure blood levels of cortisol and (ACTH), which stimulates the adrenal cortex to produce its hormones.
>ACTH stimulation test - ACTH signals your adrenal glands to produce cortisol. This test measures the level of cortisol in your blood before and after an injection of synthetic ACTH.
>Insulin-induced hypoglycemia test - involves checking blood glucose and cortisol levels after an injection of insulin. In healthy people, glucose levels fall and cortisol levels increase.
>Imaging tests - CT scan of the abdomen to check the size of the adrenal glands and look for other abnormalities.

Question 18

Discuss the pathophysiology, signs/symptoms, and tests that may be used to diagnose diabetes insipidus.

Answer 18

Because we do not have enough ADH being produced, the fluid is being lost. A result of either a neurogenic cause (ie. insufficient ADH produced because of a problem with the hypothalamus or pituitary) or a nephrogenic cause (eg. Lack of response to ADH by target cells in the kidneys). It results in an imbalance of fluids in the body.

S&S:
>polydypsia
>polyuria
>nocturia

Tests:
>Water deprivation test - while fluids are being withheld, your doctor will measure changes in your body weight, urine output, and the concentration of your urine and blood. Your doctor may also measure blood levels of ADH or give you synthetic ADH during this test. This will determine if your body is producing enough ADH and if your kidneys can respond as expected to ADH.
>MRI - can look for abnormalities in or near the pituitary gland.
>Genetic screening - if others in your family have had problems with excess urination.

Question 19

Discuss the cardiovascular effects of increased insulin secretion. In your answer, describe the microvascular changes that may occur as a result of diabetes.

Answer 19

Microvascular complications include:
>damage to eyes (retinopathy) leading to blindness
>damage to kidneys (nephropathy) leading to renal failure
>damage to nerves (neuropathy) leading to impotence and diabetic foot disorders (which include severe infections leading to amputation)

Diabetic cardiomyopathy, a relatively rare condition, associates with the presence of microvascular complications in diabetes. Therefore, changes in small arteries and capillaries are not only responsible for microvascular long-term complications, but also for other manifestations of heart disease in diabetes.

Question 20

Explain what changes may impact wound healing in a patient with diabetes.

Answer 20

High BGL causes stiffening of the arteries, narrowing of blood vessels, and diabetic neuropathy. The effect of these body changes causes an increased risk of wounds as well as more complications in diabetes wound healing.

> When high BSL destroys nerves, they do not regenerate; causing insensitivity to pain. Patients don’t feel developing blisters, infections, or existing wound changes. Wound healing is complicated as patients don’t feel wounds as they occur and they have no pain to alert them that a wound is getting worse or infected.

> Slower movement of white blood cells in the wound site, along with less effective immune responses and wounds stuck in the inflammation stage, means that infection risk is higher in diabetic wound healing.

> Narrowed blood vessels mean wound healing is impaired because less oxygen can reach the wound and the tissues do not heal as quickly

> in diabetic wound healing, the inflammation stage frequently lasts too long and the wound can become chronic.

> High BSL lowers the ability to fight infections. The immune cells don’t function as effectively in diabetic wound healing, which causes an increased risk of bacterial infections

> thickening of the capillary membranes leading to reduced blood flow to the tissues, therefore contributing to the poor healing of wounds as the supply of nutrients and oxygen to the wound is inadequate.

Question 21

Explain what diabetic ketoacidosis is and explain why this may occur in a patient with poorly controlled type 1 diabetes.

Answer 21

When the body produces high levels of blood acids called ketones.

Develops when your body can’t produce enough insulin. Insulin normally plays a key role in helping glucose enter your cells. Without enough insulin to help absorb glucose for fuel, your body begins to break down fat as fuel. This process produces a buildup of acids in the bloodstream called ketones, eventually leading to diabetic ketoacidosis if untreated.

A patient with poorly controlled type 1 diabetes is at risk of ketoacidosis because they don’t produce insulin.

Question 22

Describe the role of tropic hormones, how they are regulated, and the glands and hormones
involved

Answer 22

A tropic hormone is produced in one endocrine gland and regulates the secretion of a hormone in another endocrine gland.

The function of the anterior pituitary, and thereby the production of tropic hormones, is under hypothalamic regulation - Regulation of tropic hormone release is accomplished directly by hypothalamic releasing and inhibiting hormones:
>corticotropin-releasing hormone (CRH)
>thyrotropin-releasing hormone (TRH)
>prolactin-inhibiting hormone (PIH or dopamine)
>prolactin-releasing factor (PRF)
>gonadotropin-releasing hormone (GnRH)
>growth hormone-releasing hormone (GHRH)
>somatostatin (SS or growth hormone-inhibiting hormone)

Tropic hormones include:
>TSH (thyroid-stimulating hormone) from the pituitary stimulates the thyroid to produce thyroid hormone.
>ACTH (adrenocorticotropic hormone) stimulates the adrenal cortex to produce cortisol.
>FSH (follicle-stimulating hormone) and LH (luteinizing hormone) stimulate the gonads to produce gametes (ova and sperm) as well as the sex hormones (estrogen, progesterone, and testosterone).

They are all produced in the anterior pituitary.

Question 23

Discuss the health risks associated with obesity.

Answer 23

> anxiety and severe depression

> Sleep apnoea can cause insomnia and can come from mechanical stress (weight on the airways can damage the airways). The mechanical stress will also cause osteoarthritis, shortness of breath and low back pain which are all disabilities that can increase mortality.

> Increased free fatty acids can increase metabolic syndrome which can cause insulin resistance. This will cause T2DM which can increase the risk of cardiovascular disease. Atherosclerosis (because of increased LDLs), dyslipidemia and high BP

> An obese person is 3x more likely to have GORD. Abdominal fat puts more pressure on the lower oesophageal sphincter leading the reflux. This can progress to oesophageal cancer

> Patients with sustained obesity tend to develop glomerulosclerosis which presents as massive proteinurea - an indication of severe kidney disease.

> Obesity also increases the risk of stroke because it increases body fat which can lead to changes in to blood flow as well as increased blockage (the fat itself can put pressure on the blood vessels).

> Being obese can lead to menstrual disorders (polycystic ovary syndrome - the follicular never matures so it never ruptures and the egg is never released and so it starts to produce androgens instead) and infertility by causing changes in hormone levels.

> obesity can lead to pregnancy complications like gestational diabetes, pre-eclampsia, neural tube birth defects, and requiring a C-section.

> Added weight from abdominal fat pushes down on the bladder, causing stress incontinence. The pressure also makes it more likely that the bladder will leak causing incontinence.

> Obesity can increase lymphoedema so we end up with more fluids retained there not returning to the lymphatic system which can lead to the development of cellulitis.

> Obesity increases the risk of developing endometrial, breast, prostate, and colon cancer.

> Obesity increases the pressure on the joints and increases levels of uric acid levels in the blood leading to gout.