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213 Cards in this Set
- Front
- Back
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Multiple Sclerosis
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a chronic, often disabling unpredictable disease that attacks the central nervous system (CNS). The symptoms of multiple sclerosis generally appear between the ages of 20 and 40. Typically a person is seen after developing two or more distinct episodes of symptoms that resolve yet are consistent with MS.
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Response to stress or injury (HPA axis)
Growth and development (HPA axis) Reproduction (HPG axis) Energy metabolism (thyroid and pancreas) Fluid and electrolyte balance (ADH, aldosterone, PTH) Immune response |
Endocrine System Functions
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Multiple Sclerosis
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Characterized by the progressive, widespread occurrence of patches of myelin destruction followed by gliosis (overgrowth of astrocytes) in the white matter of the CNS forming a plaque (a CNS “scar”)
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HPA axis = hypothalamic-pituitary-adrenal axis
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Multiple Sclerosis
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Neurons are not destroyed, but demyelination disturbs conduction
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Two Broad Mechanisms:
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Alterations in hormone concentration
Deficiency Excess Alterations in receptor function/ postreceptor mechanisms (classic example of this is type II diabetes) Decrease in # of receptors Receptor insensitivity Ab against specific receptor Receptor dysfunction |
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Cause of MS is unknown.
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Most specific endocrine diseases can be understood conceptually in terms of the metabolic actions of the hormones involved, resulting in either excessive or deficient hormone production or action.
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MS is thought to be an Autoimmune
Disease. Occurs more frequently in areas that are farther from the equator (UV light may be protective) |
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Pituitary Gland/Hypothalamus
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Two components (anterior and posterior)
Hypothalamic control of pituitary which means hypothalamic injury can manifest as pituitary injury Pituitary insufficiency typically affects all the hormones secreted by pituitary– panhypopituitarism Causes include removal/destruction or necrosis of the pituitary and destruction of the hypothalamus |
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Multiple Sclerosis
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Environmental trigger (virus?) and CD4+ T cells reacting to
self myelin antigens→ macrophage activation→ myelin destruction |
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Hyperprolactinemia-most common cause other than pregnancy is a benign pituitary tumor secreting prolactin
In women; amenorrhea, galactorrhea In men; impotence (ED), ↓libido, infertility; visual disturbance, headache |
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Multiple Sclerosis
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No cure.
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Hypersecretion of GH (gigantism and acromegaly)
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Multiple Sclerosis
treatment |
beta interferon (Avonex, Betaseron, and Rebif) have now been
approved by the FDA for treatment of relapsing-remitting MS. Also approved Is a synthetic form of myelin basic protein, called Copolymer. An immuno- suppressant treatment, Novantrone (mitoxantrone) is used in more severe MS. Dalfampridine (Ampyra) improves walking in individuals with MS. A mono- clonal antibody, natalizumab (Tysabri), significantly reduces the frequency of attacks in people with relapsing forms of MS. Episodes are also treated with corticosteroids. |
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Most common posterior pituitary disorder is ADH deficiency caused by head trauma, surgical injury of the pituitary, or inflammatory or neoplastic lesions of the hypothalamus or pituitary
Manifests as diabetes insipidus (central rather than nephrogenic) Polyuria, polydipsia, and hyperosmolality of blood |
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Clinical Features of MS
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Sensory disorders (numbness, pins and needles)
Visual complaints Spastic weakness of the limbs Bladder dysfunction Mood disorders Variable progression, remitting/relapsing cycles in which remission is less complete with each episode |
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Gigantism and Acromegaly
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Results from pituitary adenomas oversecreting GH
Childhood=gigantism Adult=acromegaly Course facial features Enlarged mandible Thick ears and nose Enlarged spade-like hands and feet Enlarged tongue Deep husky voice Spinal deformities |
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Initial symptom of MS
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is often blurred or double vision, red-green color distortion, or even blindness in one eye. Most MS patients experience muscle weakness in their extremities and difficulty with coordination and balance. Some have pain, cognitive impairment, & depression.
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Gigantism and Acromegaly
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Treatment: somatostatin, surgery
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Thyroid Gland
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Thyroid hormones [tri-iodothyronine (T-3) and thyroxine (T-4)] regulate our body's metabolism and influence virtually every organ system in the body. The major effect is stimulation of cellular metabolism & heat production.
Hyperthyroidism Graves’s disease Hypothyroidism Thyroid cancer Goiter |
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Hyperthyroidism (too much thyroid hormone)
The most common underlying cause of hyperthyroidism is Graves' disease (an autoimmune disease). Another cause is “toxic nodular goiter” where a single nodule overproduces thyroid hormones. |
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Grave’s Disease
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Form of autoimmune thyroiditis; Women are seven times more likely to develop Graves' disease than men.
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Grave’s Disease
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Symptoms are typical of hyperthyroidism
Enlarged thyroid-excess thyroid hormones (T-3, T-4) inflammation of the tissues around the eyes, causing swelling (exophthalmos) thickening of the skin over the lower legs (pretibial myxedema). Hypermetabolism (heat intolerance, sweating, weight loss, tachycardia, anxiety, restlessness) |
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Grave’s Disease
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Caused by an IgG antibody acting directly on follicle cells of the thyroid (causes hyperplasia and ↑synthesis of TH)
Out of TSH control-TH synthesized irrespective of need, no negative feedback |
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Hypothyroidism symptoms
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Symptoms: fatigue, muscle weakness, constipation, weight
gain, depression, brittle nails & hair, puffy face, cold sensitivity Increased, hoarse voice, peripheral neuropathy, goiter |
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Hypothyroidism cause
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Causes: most common is Hashimoto's thyroiditis, an
autoimmune disorder. Other causes include lithium, radiation, insufficient TSH, iodine deficiency. Most common in middle- aged women and tends to run in families. |
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Hypothyroidism treatment
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Treatment: daily use of the synthetic thyroid hormone
levothyroxine [T-4] (Levothroid, Levoxyl, Synthroid). |
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Adrenal Gland
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Normal adrenal cortex hormones
Glucocorticoids (cortisol, corticosterone) Mineralocorticoids (mainly aldosterone) Sex steroids (dehydroepiandrosterone) Normal adrenal medulla hormones Catecholamines: epinephrine, norepinephrine |
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Overproduction of Adrenal Hormones
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Overproduction of adrenal hormones leads to clinical syndromes indicative of which group of hormones is in excess.
Excess glucocorticoids – Cushing’s syndrome Excess aldosterone – aldosteronism Excess androgens – hirsutism and virilization in females Excess release of catecholamines – pheochromocytoma which is a tumor producing excess catecholamines (usually epi); characterized by sudden, severe hypertension and headaches, sweating and palpitations |
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Excessive Androgens
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Problem for females more than males
Virilization (acne, deepening of the voice, enlargement of the clitoris, temporal hairline recession or baldness, oligo- or amenorrhea) Hirsutism (excessive growth of course dark hair with masculine distribution over the face, nipples and pubic area) Main causes are polycystic ovary syndrome, androgen producing tumors of the ovary or adrenal glands, and late-onset congenital adrenal hyperplasia |
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Cushing’s Syndrome-excess cortisol
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Caused by tumors that produce cortisol or adrenocorticotropic hormone (ACTH) or exogenous corticosteroids
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sign and symptoms of Cushing's syndrome
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Signs and symptoms include aspects of excess cortisol
Metabolic abnormalities-rapid weight gain, moon face Inhibition of immune/inflammatory/wound healing Increases in gastric secretions Altered brain function-emotional lability (unstable) |
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Cushing Syndrome
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Most common cause is iatrogenic-therapeutic administration of corticosteroids; also pituitary tumors that secrete ACTH or lung (oat cell) tumors that secrete ACTH ectopically; ACTH-independent type where an adrenal tumor hypersecretes cortisol
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Hyperprolactinemia-most common cause other than pregnancy is a benign pituitary tumor secreting prolactin
In women; amenorrhea, galactorrhea In men; impotence (ED), ↓libido, infertility; visual disturbance, headache |
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Hypersecretion of GH (gigantism and acromegaly)
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Most common posterior pituitary disorder is ADH deficiency caused by head trauma, surgical injury of the pituitary, or inflammatory or neoplastic lesions of the hypothalamus or pituitary
Manifests as diabetes insipidus (central rather than nephrogenic) Polyuria, polydipsia, and hyperosmolality of blood |
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Gigantism and Acromegaly
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Results from pituitary adenomas oversecreting GH
Childhood=gigantism Adult=acromegaly Course facial features Enlarged mandible Thick ears and nose Enlarged spade-like hands and feet Enlarged tongue Deep husky voice Spinal deformities |
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Gigantism and Acromegaly
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Treatment: somatostatin, surgery
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Thyroid Gland
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Thyroid hormones [tri-iodothyronine (T-3) and thyroxine (T-4)] regulate our body's metabolism and influence virtually every organ system in the body. The major effect is stimulation of cellular metabolism & heat production.
Hyperthyroidism Graves’s disease Hypothyroidism Thyroid cancer Goiter |
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Hyperthyroidism (too much thyroid hormone)
The most common underlying cause of hyperthyroidism is Graves' disease (an autoimmune disease). Another cause is “toxic nodular goiter” where a single nodule overproduces thyroid hormones. |
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Grave’s Disease
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Form of autoimmune thyroiditis; Women are seven times more likely to develop Graves' disease than men.
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Grave’s Disease
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Symptoms are typical of hyperthyroidism
Enlarged thyroid-excess thyroid hormones (T-3, T-4) inflammation of the tissues around the eyes, causing swelling (exophthalmos) thickening of the skin over the lower legs (pretibial myxedema). Hypermetabolism (heat intolerance, sweating, weight loss, tachycardia, anxiety, restlessness) |
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Grave’s Disease
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Caused by an IgG antibody acting directly on follicle cells of the thyroid (causes hyperplasia and ↑synthesis of TH)
Out of TSH control-TH synthesized irrespective of need, no negative feedback |
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Hypothyroidism (underactive thyroid) is a condition in which
the thyroid gland doesn't produce enough T-3 and T-4. |
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Hypothyroidism symptoms
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Symptoms: fatigue, muscle weakness, constipation, weight
gain, depression, brittle nails & hair, puffy face, cold sensitivity Increased, hoarse voice, peripheral neuropathy, goiter |
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Hypothyroidism cause
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Causes: most common is Hashimoto's thyroiditis, an
autoimmune disorder. Other causes include lithium, radiation, insufficient TSH, iodine deficiency. Most common in middle- aged women and tends to run in families. |
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Hypothyroidism treatment
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Treatment: daily use of the synthetic thyroid hormone
levothyroxine [T-4] (Levothroid, Levoxyl, Synthroid). |
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Adrenal Gland
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Normal adrenal cortex hormones
Glucocorticoids (cortisol, corticosterone) Mineralocorticoids (mainly aldosterone) Sex steroids (dehydroepiandrosterone) Normal adrenal medulla hormones Catecholamines: epinephrine, norepinephrine |
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Overproduction of Adrenal Hormones
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Overproduction of adrenal hormones leads to clinical syndromes indicative of which group of hormones is in excess.
Excess glucocorticoids – Cushing’s syndrome Excess aldosterone – aldosteronism Excess androgens – hirsutism and virilization in females Excess release of catecholamines – pheochromocytoma which is a tumor producing excess catecholamines (usually epi); characterized by sudden, severe hypertension and headaches, sweating and palpitations |
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Excessive Androgens
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Problem for females more than males
Virilization (acne, deepening of the voice, enlargement of the clitoris, temporal hairline recession or baldness, oligo- or amenorrhea) Hirsutism (excessive growth of course dark hair with masculine distribution over the face, nipples and pubic area) Main causes are polycystic ovary syndrome, androgen producing tumors of the ovary or adrenal glands, and late-onset congenital adrenal hyperplasia |
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Cushing’s Syndrome-excess cortisol
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Caused by tumors that produce cortisol or adrenocorticotropic hormone (ACTH) or exogenous corticosteroids
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sign and symptoms of Cushing's syndrome
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Signs and symptoms include aspects of excess cortisol
Metabolic abnormalities-rapid weight gain, moon face Inhibition of immune/inflammatory/wound healing Increases in gastric secretions Altered brain function-emotional lability (unstable) |
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Cushing Syndrome
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Most common cause is iatrogenic-therapeutic administration of corticosteroids; also pituitary tumors that secrete ACTH or lung (oat cell) tumors that secrete ACTH ectopically; ACTH-independent type where an adrenal tumor hypersecretes cortisol
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"iatrogenesis" means "brought forth by a healer" (iatros means healer in Greek)
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Cushing Syndrome
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C - Central obesity, Cervical fat pads, Collagen fibre weakness
U - Urinary free cortisol and glucose increase
S - Striae, Suppressed immunity
H - Hypercortisolism, Hypertension, Hyperglycaemia, Hirsutism
I - Iatrogenic (Increased administration of corticosteroids)
N - Noniatrogenic (Neoplasms)
G - Glucose intolerance, Growth retardation
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Aldosteronism
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- characterized by increased aldosterone secretion from the adrenal glands, suppressed plasma renin activity, hypertension, and hypokalemia.
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Aldosteronism
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May be primary or secondary
Primary (Conn’s Syndrome) – is almost always caused by an adrenal adenoma Secondary – typically occurs as a result of activation of the renin-angiotensin-aldosterone system during CHF, liver cirrhosis, nephrotic syndrome or renal artery stenosis |
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Aldosteronism
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Effects include retention of Na+ and water leading to hypertension and excessive loss of K+ and H+ leading to hypokalemia, metabolic alkalosis and cardiac dysrhythmias
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Adrenal Insufficiency
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Most common cause of primary insufficiency is an autoimmune destruction of the adrenal cortex called Addison’s Disease (TB and AIDS can trigger AD) John Kennedy 35th president
secondary causes may be hypothalamic/pituitary insufficiency (decreased ACTH) or the sudden withdrawal of corticosteroid drugs Usually >80% of adrenal gland must be destroyed before insufficiency is evident |
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Addison’s Disease-adrenal cortex disorder
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adrenal glands produce too little cortisol and often insufficient levels of aldosterone & androgens as well.
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Addison’s Disease
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Manifestations include deficiencies in cortisol, aldosterone and androgens.
Progressive weakness and fatigue Anorexia and weight loss Decreased stress response Hypotension; including orthostatic Hyperpigmentation (darkening of the skin) Fluid and electrolyte disturbances (hyponatremia, hyperkalemia, metabolic acidosis); salt craving Fasting hypoglycemia (loow blood sugar) Reproductive system disturbances in women (amenorrhea and loss of axillary and pubic hair) |
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Treatment of Addison Disease
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Oral corticosteroids-
fludrocortisones (Florinef) to replace aldosterone (decreases Na loss) Hydrocortisone (Cortef), prednisone or cortisone acetate may be used to replace cortisol. Corticosteroid injections. If you're ill with vomiting and can't retain oral medications, injections are an option. Androgen replacement therapy. To treat androgen deficiency in women, dehydroepiandrosterone (DHEA) can be prescribed. Some studies suggest that this therapy may improve overall sense of well-being, libido and sexual satisfaction. |
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Regulation of glucose metabolism (normal serum level is 70 -110 mg/dl)
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Endocrine Pancreas
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[postprandial glucose level under 180 mg/dl & preprandial glucose 90-130 mg/dl recommended by American Diabetes Association]
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Endocrine Pancreas
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Production of hormones with opposing actions (islets of Langerhans)
Insulin( alpha cells) Glucagon( beta cells) |
Endocrine Pancreas
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Diabetes mellitus is characterized by
fasting and postprandial hyperglycemia, atherosclerotic and microvascular disease, and neuropathy |
Endocrine Pancreas
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a chronic metabolic disease in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). DM is the number one cause of amputations and blindness in the US.
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Diabetes mellitus
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Two main types
Type 1 diabetes (IDDM)-insulin deficiency Type 2 diabetes (NIDDM)-insulin resistance Gestational diabetes is a third type |
Diabetes mellitus
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Remember that diabetes insipidus is not related to insulin.
Central diabetes insipidus is caused by ADH (vasopressin) insufficiency Nephrogenic diabetes insipidus is caused by renal insensitivity to ADH |
Diabetes mellitus
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Characterized by an little or no endogenous insulin (requires lifelong replacement therapy)
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Type 1 Diabetes (IDDM)-juvenile diabetes
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Cause is unknown- Various factors may contribute to type 1 diabetes, including genetics and exposure to certain viruses.
Autoimmune destruction of β-cells in the islets of Langerhans Idiopathic |
Type 1 Diabetes (IDDM)-juvenile diabetes
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Increased thirst (polydipsia) and frequent urination (polyuria)
Extreme hunger (polyphagia) Weight loss Fatigue Blurred vision- If your blood sugar level is too high, fluid may be pulled from your tissues — including the lenses of your eyes. |
type 1 Symptoms
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a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency
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Type 2 Diabetes (NIDDM)-late onset
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Characterized by:
Peripheral insulin resistance Impaired insulin secretion Excessive hepatic glucose production |
Type 2 Diabetes (NIDDM)-late onset
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No evidence of autoimmune destruction
Very little tendency toward ketoacidosis Obesity increases risk of this type Genetic predisposition plays a role in susceptibility, although no reliable genetic marker has been shown |
Type 2 Diabetes (NIDDM)-late onset
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Initially managed by increasing exercise and dietary modification; later drugs may be needed
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Type 2 Diabetes (NIDDM)-late onset
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Diabetic Ketoacidosis
Nonketotic hyperosmolar coma Hypoglycemia |
All these can lead to death if untreated
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(mostly type type 1 DM)
Hyperglycemia (>300mg/dl) Metabolic acidosis caused by accumulation of ketone acids Osmotic diuresis Fruity breath |
Diabetic Ketoacidosis
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[hyperosmolar nonketotic state (HNS)] (mostly type 2 DM)
Severe hyperglycemia (>600mg/dl) causing: Severe hyperosmolality Osmotic diuresis (polyuria) Volume and free water depletion; increased thrombosis |
Nonketotic hyperosmolar coma
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(seen with insulin therapy)
Becomes symptomatic when insufficient glucose is available to meet the needs of the CNS (<55 mg/dl) Shakiness, sweating, tachycardia and nervousness are caused by increased release of epinephrine to try and increase glucose |
Hypoglycemia
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Microvascular
Diabetic retinopathy Renal failure, ED, bladder control problems, lower-extremity amputations, gastroparesis (delayed emptying of stomach) Macrovascular Atherosclerosis with development of CAD, stroke, and peripheral vascular disease Peripheral neuropathy-nerve damage; loss of sensation; tingling, pain Infection (poor wound healing) |
Chronic Complications of Diabetes
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>90,000 amputations/yr in US due to DM and inadequate foot care
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Hyperglycemia is the major issue that drives each of the chronic complications.
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Metabolic Basis for Chronic Complications of D.M.
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Vascular “issues” generally arise from the hyperglycemia
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Metabolic Basis for Chronic Complications of D.M.
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Three specific events occur that alter the function and regulation of numerous tissues:
Nonenzymatic glycosylation of proteins Excess glucose enters the polyol pathway Activation of protein kinase C |
Metabolic Basis for Chronic Complications of D.M.
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(HbA1c), lipids and nucleic acids
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Nonenzymatic glycosylation of proteins
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(sorbitol-aldose reductase pathway) Excessive activation of the polyol pathway increases intracellular and extracellular sorbitol concentrations, increased concentrations of reactive oxygen species, and decreased concentrations of nitric oxide and glutathione.
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Excess glucose enters the polyol pathway
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increase the production of extracellular matrix and cytokines; to enhance contractility, permeability, and vascular cell proliferation, altering vascular function in retina, cardiovascular, renal tissues.
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Activation of protein kinase C
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The 2010 American Diabetes Association Standards of Medical Care in Diabetes added
the HbA1c ≥ 6.5% as another criterion for the diagnosis of diabetes |
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Substance P: According to traditional thinking, type 1 diabetes is an autoimmune disorder of the pancreas. Inflamed and under assault by T-cells, beta cells are destroyed along with the body's source of insulin.
Investigators found evidence that the autoimmune attack on beta cells appears to be triggered by abnormal sensory nerves that lack a neuropeptide, substance P. When these mice were given an injection of substance P directly into the pancreas, insulin and glucose levels returned to normal. |
Diabetes cures?
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Bariatric surgery (bypass or gastric banding)- 70 % of these patients had their type 2 diabetes go away ( they no longer needed diabetes medications and HbA1c levels returned to normal).
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Diabetes cures?
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Islet cell transplants, pancreas transplants
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Diabetes cures?
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The metabolic syndrome is characterized by a group of metabolic risk factors . They include:
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Abdominal obesity
Atherogenic dyslipidemia Elevated blood pressure Insulin resistance or glucose intolerance Prothrombotic state Proinflammatory state |
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Over 50 million Americans (up to 25% of the population) have metabolic syndrome
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(excessive fat tissue in and around the abdomen)
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Abdominal obesity
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(blood fat disorders — high triglycerides, low HDL cholesterol and high LDL cholesterol — that foster plaque buildups in artery walls)
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Atherogenic dyslipidemia
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(the body can’t properly use insulin or blood sugar)
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Insulin resistance or glucose intolerance
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(e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood)
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Prothrombotic state
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(e.g., elevated C-reactive protein, TNFα, IL-6 in the blood)
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Proinflammatory state
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The American Heart Association and the National Heart, Lung, and Blood Institute recommend that the metabolic syndrome be identified as the presence of three or more of these components:
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Elevated waist circumference:
Men — Equal to or greater than 40 inches (102 cm)
Women — Equal to or greater than 35 inches (88 cm)
Elevated triglycerides: Equal to or greater than 150 mg/dL Reduced HDL (“good”) cholesterol: Men — Less than 40 mg/dL Women — Less than 50 mg/dL Elevated blood pressure: Equal to or greater than 130/85 mm Hg Elevated fasting glucose: Equal to or greater than 100 mg/dL |
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Etiology of Metabolic syndrome The most important factors are:
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weight
genetics aging sedentary lifestyle, i.e., low physical activity and excess caloric intake |
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People with the metabolic syndrome are at increased risk of coronary heart disease and other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease) and type 2 diabetes
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the first-line therapy is to reduce the major risk factors for cardiovascular disease: stop smoking and reduce LDL cholesterol, blood pressure and glucose levels to the recommended levels.
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Despite the way it sounds, heart failure does not mean that the heart
suddenly stopped working or that you are about to die. Rather, heart failure is a common condition that usually develops slowly as the heart muscle weakens and needs to work harder to keep blood flowing through the body. Heart failure develops following injury to the heart such as the damage caused by a heart attack, long-term high blood pressure, or an abnormality of one of the heart valves. The weakened heart must work harder to keep up with the demands of the body, which is why people with heart failure often complain of feeling tired. |
heart failure
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Heart failure is often not recognized until a more advanced stage of
heart failure, commonly referred to as congestive heart failure, in which fluid may leak into the lungs, feet, legs, and in some cases the liver or abdominal cavity. |
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Over 150 years ago, the German pathologist Rudolph Virchow
postulated that thrombus formation and propagation resulted from abnormalities of (1) blood flow, (2) the vessel wall, and (3) blood components. These three factors are known as Virchow’s triad. |
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Since Virchow first published his observations, the features of this
triad have been further refined: |
Blood flow — abnormalities of haemorheology (blood flow properties)
and turbulence at vessel bifurcations and stenotic regions Vessel walls — abnormalities in the endothelium, such as atherosclerosis and associated vascular inflammation Blood components — abnormalities in coagulation and fibrinolytic pathways |
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Venous thromboembolism (VTE) is a disease that includes deep vein thrombosis ( DVT)
and pulmonary embolism (PE). |
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Advances in laboratory techniques now enable clinicians to quantify
some of these thrombosis-related factors that, when abnormal, confer a “prothrombotic” or “hypercoagulable” state. |
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This state is associated with an increased risk of VTE (Venous
Thrombolembolism) and other cardiovascular diseases, including atrial fibrillation, coronary heart disease, and heart failure. |
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Thromboprophylaxis-The use of medication or medical devices to
prevent the formation of blood clots. |
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The rates of total DVT, assessed 7 to 14 days after surgery, are 40%
to 80% following hip or knee arthroplasty or hip fracture surgery. Because of this high risk, the ACCP recommends primary prevention of VTE for all patients undergoing major orthopaedic surgery of the lower limb. |
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An estimated 300,000 VTE-related deaths occur in the US each year
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Many identifiable factors contribute to an increased risk of VTE.
These can be divided into predisposing risk factors (ie, patient characteristics) and exposing or situational factors (ie, acute medical conditions, acute trauma, and surgery). |
who is at risk
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Major orthopaedic surgery is an example of an exposing risk factor.
These surgical procedures are associated with about twice the rate of VTE as general surgery. Consistent with Virchow’s triad, the increased risk of VTE in major orthopaedic surgery may be linked to: |
•Venous stasis, from postoperative immobility
•Damage to the vessel wall during the procedure •Increased procoagulant activity, such as increased thrombin generation |
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Important exposing risk factors for VTE include:
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Surgery and trauma
•Hip and knee arthroplasty •Hip and other lower extremity fracture •Multiple trauma •Major surgery for malignancy •Arthroscopic repair of cruciate ligament and meniscectomy •Other surgical procedures, duration >30 minutes •Plaster cast immobilization of lower limb |
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Deaths attributable to VTE are estimated to exceed the total combined number
of deaths from breast cancer, prostate cancer, AIDS, and traffic accidents annually |
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Important exposing risk factors for VTE include:
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Nonsurgical conditions and factors
•Stroke with paralysis •Acute decompensated COPD •Acute heart failure, NYHA III or IV •Sepsis •Acute infection with immobilisation •Acute inflammatory disease with immobilisation •Central venous catheter |
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Hospitalised patients and residents of nursing homes
account for about 60% of all cases of VTE. |
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Important predisposing risk factors for VTE include:
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•Thrombophilia
•History of VTE •Active malignancy •Pregnancy •Age >60 years •Obesity (BMI >30) •Estrogen therapy (BC pills increases risk) •Chronic heart failure •Varicose veins |
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“Thrombophilia” refers to an inherited or acquired imbalance in the
coagulation system that leads to an increased risk of thrombosis. |
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Area of ischemic coagulative necrosis caused by occlusion
of either arterial supply or venous drainage. |
Infarction
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99% of all infarcts are the result of thrombotic or embolic
Events. |
Infarction
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Most CV deaths are attributable to either myocardial or
cerebral infarctions. |
infarctions
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Consequences: range from none/minimal to death
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infarctions
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Factors that influence development of infarcts
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Nature of vascular supply
Rate of development of occlusion Vulnerability of tissue to hypoxia Oxygen content of blood |
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Complex, acquired disorder in which clotting and hemorrhage
simultaneously occur. The processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding. |
Disseminated Intravascular Coagulation (DIC)
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Sudden onset of widespread thrombi in microcirculation with the
rapid consumption of platelets and coagulation factors, fibrinolysis is activated |
Disseminated Intravascular Coagulation (DIC)
|
|
|
Endothelial damage is the primary initiator of DIC
|
Disseminated Intravascular Coagulation (DIC)
|
|
|
DIC is the result of increased protease activity in the blood caused by unregulated release of thrombin with subsequent fibrin
formation and accelerated fibrinolysis. |
Disseminated Intravascular Coagulation (DIC)
|
|
|
release of a transmembrane glycoprotein called tissue factor (TF).
TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes). TF is released in response to exposure to cytokines (particularly interleukin 1), tumor necrosis factor, and endotoxin. This plays a major role in the development of DIC in septic conditions. The release of endotoxin is the mechanism by which Gram-negative sepsis provokes DIC. |
Disseminated Intravascular Coagulation (DIC)
initiators |
|
|
The amount of activated thrombin exceeds the body’s
“antithrombins” and the thrombin does not remain localized |
Disseminated Intravascular Coagulation (DIC)
|
|
|
The widespread thromboses created cause widespread ischemia,
infarction, and organ hypoperfusion |
Disseminated Intravascular Coagulation (DIC)
|
|
|
As the small clots consume coagulation proteins and platelets, normal
coagulation is disrupted and abnormal bleeding occurs from the skin (e.g. from sites where blood samples were taken), the gastrointestinal tract, the respiratory tract and surgical wounds. The small clots also disrupt normal blood flow to organs (such as the kidneys), which may malfunction as a result. |
DIC
|
|
|
DIC can occur acutely but also on a slower, chronic basis, depending on the
underlying problem. It is common in the critically ill, and may participate in the development of multiple organ failure, which may lead to death |
DIC
|
|
|
By activating the fibrinolytic system (plasmin), the patient’s
fibrin degradation products (FDP) and D-dimer levels will increase |
DIC
|
|
|
Because of the patient’s clinical state, the disorder has a
high mortality rate. 10-50% of patients with DIC will die from it, hence DIC is often thought of as “Death Is Coming”. |
DIC
|
|
|
Treatment is to remove the stimulus. Platelets may be transfused if
counts are less than 5,000-10,000/mm3 and massive hemorrhage is occurring, and plasma may be administered in an attempt to replenish coagulation factors and anti-thrombotic factors. |
DIC
|
|
|
D-dimers are not normally present in human blood plasma, except
when the coagulation system has been activated, for instance because of the presence of thrombosis or DIC. |
D-dimers
|
|
|
Disseminated Intravascular Coagulation (DIC)
Clinical signs and symptoms demonstrate wide variability |
Bleeding from venipuncture sites
Bleeding from arterial lines Purpura, petechiae, and hematomas Symmetric cyanosis of the fingers and toes |
|
|
Purpura is purple-colored spots and patches that occur on the skin, organs, and in mucus
membranes, including the lining of the mouth. Purpura occurs when small blood vessels under the skin leak. |
*
|
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Very small spots are called petechiae.
|
*
|
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Conditions Associated with DIC
|
Metastatic cancer
Acute bacterial and viral infections Certain parasitic diseases (malaria) Sepsis/Septic shock Massive trauma Burns |
|
|
DIC is always secondary to an underlying disorder and is
associated with a number of clinical conditions (see List below), generally involving activation of systemic inflammation. |
DIC
|
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|
About 1 in 3 adults in the United States has HBP
|
*
|
|
|
Hypertension (HTN) or high blood pressure (HBP)
is a chronic medical condition in which the systemic arterial blood pressure is elevated. It is the opposite of hypotension. |
*definition of hypertension
|
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|
Most (90-95%) is primary hypertension or essential
hypertension (cause unknown) |
*
|
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This accounts for the CV disease in 83% of the people in
the US who have CV Disease |
*
|
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|
Secondary hypertension is caused by Cushing’s syndrome,
pheochromocytoma, hyperthyroidism, etc. |
*
|
|
|
Ideal cardiovascular health means:
|
* Ideal health behaviors:
Non-smoking BMI <25 Physical activity at goal levels Diet consistent with current guidelines Ideal health factors: Untreated total cholesterol<200mg/dL Untreated BP< 120/<80 mmHg Fasting blood glucose<100mg/dL |
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|
What is known is that cardiac output is raised early in the disease course, with
total peripheral resistance (TPR) normal; over time cardiac output drops to normal levels but TPR is increased. |
*hypertension
|
|
|
Three theories have been proposed to explain this:
|
*nability of the kidneys to excrete sodium, resulting in natriuretic factors such as
Atrial Natriuretic Factor being secreted to promote salt excretion with the side effect of raising total peripheral resistance. An overactive Renin-angiotensin system leads to vasoconstriction and retention of sodium and water. The increase in blood volume leads to hypertension. An overactive sympathetic nervous system, leading to increased stress responses. |
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It is also known that hypertension is highly heritable and polygenic.
|
*
|
|
|
Recently, work related to the association between essential hypertension and sustained
endothelial damage has gained popularity among hypertension scientists. It remains unclear however whether endothelial changes precede the development of hypertension or whether such changes are mainly due to long standing elevated blood pressures. |
hypertension
|
|
|
Hypertension
|
Involves hemodynamic mechanisms
↑cardiac output and/or peripheral resistance |
|
|
Hypertension
|
Kidneys, renin-angiotensin-aldosterone system, and
SNS all play a contributing role |
|
|
Hypertension
|
Consequences involve vessel injury and prolonged
vasoconstriction-target organ disease |
|
|
Risk Factors for hypertension
|
+ Family history
Race Age High Na+ intake Obesity Inactivity Excessive alcohol consumption Sleep Apnea |
|
|
manifestations of hypertension
|
The most severe manifestations are injury to the vessel
wall, subsequent development of atherosclerosis and predisposition to all major atherosclerotic CV disorders |
|
|
manifestations of hypertension
|
Left ventricular hypertrophy which is a risk factor for
ischemic heart disease, arrhythmias, CHF, death. |
|
|
Hypertension treatments:
|
Lifestyle changes (lose weight, exercise, stop smoking)
Often multiple drugs are combined to achieve the goal blood pressure. |
|
|
Commonly used prescription drugs include:
|
ACE inhibitors (captopril, lisinopril)
Alpha blockers (prazosin) *Angiotensin II receptor antagonists (losartan) *Beta blockers (propranolol) *Calcium channel blockers (verapamil) *Diuretics (hydrochlorothiazide) Direct renin inhibitors (aliskiren) |
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|
Atherosclerosis
|
a disease of large and medium-sized muscular arteries and
is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the vessel wall. This buildup results in plaque formation, vascular remodeling, acute and chronic luminal obstruction, abnormalities of blood flow, and diminished oxygen supply to target organs. |
|
|
Atherosclerosis
|
The process of atherosclerosis begins in childhood with the
development of fatty streaks. These lesions can be found in the aorta shortly after birth and appear in increasing numbers in those aged 8-18 years. More advanced lesions begin to develop when individuals are aged approximately 25 years. Subsequently, an increasing prevalence of the advanced complicated lesions of atherosclerosis exists, and the organ-specific clinical manifestations of the disease increase with age through the fifth and sixth decades of life. |
|
|
Atherosclerosis Risk factors:
|
Diabetes mellitus
Cigarette smoking Obesity C-reactive protein Fibrinogen Lipoprotein (a) Hyperlipidemia Hypertension- |
|
|
Atherosclerosis Risk factors:
|
Hypertension-evidence suggests that homocysteine may have an effect
on atherosclerosis by damaging the inner lining of arteries and promoting blood clots |
|
|
Morphology
|
Three principal components
Cells (macrophages/foam cells, SMC, lymphocytes ECM (collagen) Lipid (LDL, oxidized LDL) |
|
|
Factors that induce or promote atherogenesis
|
Endothelial injury that alters the normal homeostasis of
the endothelium Increased adhesion and permeability increased coagulantion Formation of vasoactive cytokines and growth factors Continuing inflammatory response Increased expression of endothelial adhesion molecules Progressive accumulation of macrophages (secrete IL-1 and TNF-α, free radicals) Recruitment of T-lymphocytes Cyclic accumulation of cells and lipids |
|
|
GI disorders make up a large proportion of the illnesses that cause patients to seek medical help and are the leading cause of hospitalization in the U.S.
|
*
|
|
|
GI problems
|
Among the top five causes of death
GI cancer accounts for ¼ of all cancer deaths Liver failure also accounts for a substantial number of deaths Other than cancers, inflammation is the cause of a large number of GI problems GI tract is especially vulnerable to transient disorders |
|
|
Problems that Affect Bowel Functions
|
Inflammation and damage to the bowel wall
Hemorrhage → anemia Perforation → peritonitis Decreased mucosal function → malabsorption Decreased bacterial containment → sepsis |
|
|
Problems that Affect Bowel Functions
|
Malabsorption
Pancreatic, lactase, or bile salt insufficiency Malnutrition, dehydration, electrolyte imbalances |
|
|
Problems that Affect Bowel Functions
|
Obstruction
Malabsorption Compartment syndrome → ischemia Distension (fluid/gas); shock (hypovolemic due to loss of fluid or septic due to bacteria escaping the bowel |
|
|
Irritable bowel syndrome (IBS)
|
a functional bowel disorder characterized by chronic abdominal
pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. |
|
|
Irritable bowel syndrome (IBS)
|
Diarrhea or constipation may predominate, or they may
alternate (classified as IBS-D, IBS-C or IBS-A, respectively). |
|
|
Irritable bowel syndrome (IBS)
|
IBS presents as: coeliac disease, fructose malabsorption, mild
infections, parasitic infections like giardiasis, several inflammatory bowel diseases, functional chronic constipation, and chronic functional abdominal pain. |
|
|
Irritable bowel syndrome (IBS)
|
Cause-unknown; it may be a disorder of the interaction between
the brain and the gastrointestinal tract, although there may also be abnormalities in the gut flora or the immune system |
|
|
Irritable bowel syndrome
IBS-C Treatment: |
soluble fiber supplementation is helpful
(insoluble fiber is not) Laxatives-osmotic laxatives such as polyethylene glycol, and lactulose Stool softeners (Docusate sodium) Lubiprostone - a bicyclic fatty acid (prostaglandin E1 Derivative Domperidone, a dopamine receptor blocker Tegaserod (Zelnorm), a selective 5-HT4 agonist |
|
|
IBS-D
|
Treatment-anti-spasmodics (hyoscyamine,
atropine); loperimide (imodium) |
|
|
IBS
|
Both IBS-C & IBS-D may benefit from prebiotics,
yogurt, antidepressants (amitriptyline), peppermint oil, Rifaximin (an antibiotic) |
|
|
Inflammatory bowel disease (IBD)
|
is a group of inflammatory conditions of the colon and small
intestine. The major types of IBD are Crohn's disease and ulcerative colitis (UC). |
|
|
Inflammatory bowel disease (IBD)
|
Persons with IBD may have increased
risk of arthritis & other non-intestinal symptoms, including endothelial dysfunction and coronary artery disease. |
|
|
Inflammatory bowel disease (IBD)
|
The main difference between Crohn's disease and UC is the
location and nature of the inflammatory changes |
|
|
Crohn's can
affect any part of the gastrointestinal tract, from mouth to anus (skip lesions), although a majority of the cases start in the terminal ileum. |
IBD
|
|
|
Ulcerative colitis, in contrast, is restricted to the
colon and the rectum. |
IBD
|
|
|
IBD treatment
|
anti-inflammatory (mesalazine, steroids, TNFα
inhibition), helminthic therapy (drink with roughly 2,500 ova of the Trichuris suis helminth), probiotics, prebiotics, cannabis |
|
|
Ulcerative Colitis (an IBD)
|
Follows a prolonged course of exacerbations and remissions
|
|
|
Ulcerative Colitis (an IBD)
|
Lesions involve mucosa and submucosa and eventually cause ulcerations and bleeding
|
|
|
Ulcerative Colitis (an IBD)
|
Begins in rectosigmoid area , then spreads proximally (no interspersed normal tissue as with Crohn’s)
|
|
|
Ulcerative Colitis (an IBD)
symptoms |
Colicky abdominal pain
Bloody, mucus-filled diarrhea |
|
|
Ulcerative Colitis (an IBD)
Complications |
Hemorrhage
Carcinoma of colon |
|
|
What is slow transit constipation?
|
Slow transit constipation is often a problem of young women,
frequently starting at puberty. In this condition, patients have one or fewer bowel movements per week. They are not concerned about the infrequent urge to but rather complain of bloating and abdominal pain. |
|
|
Slow transit constipation medications:
|
Prokinetic drugs-medications that stimulate intestinal motility
(Bethanechol, motilin, erythromycin) |
|
|
physiologic tests for “functional constipation”:
|
Colonic transit study
Anorectal manometry Defecography |
|
|
Colonic transit study
|
normal transit time is 72hrs; At 120 hours, no more
than five markers should remain in the colon; a greater number suggests inertia. If markers pass through the colon normally but accumulate in the rectum and sigmoid, pelvic floor dyssynergia should be considered. |
|
|
Anorectal manometry
|
evaluates sphincter pressures, rectal anal inhibitory
reflex, and rectal sensation. Expulsion of a balloon filled with 50 ml of water provides information regarding defecatory function. Failure to expel the balloon within one minute suggests pelvic floor dysfunction. |
|
|
Defecography
|
evaluates the anorectal anatomy, providing information
regarding anorectal angulation, pelvic floor descent, and anatomic defects such as rectocele that can be associated with constipation. |
|
|
Rome II Diagnostic Criteria for Chronic Functional Constipation
|
fewer than three defecations per week
|
|
|
Which is synthesized in the anterior pituitary gland
|
TSH
|
|
|
Secondary aldosteronism typically occurs in
|
renal artery stenosis
|
|
|
The zona reticularis is the site of ______________ production.
|
androgens
|
|
|
Which is not a manifestation of Addison’s disease?
|
fasting hyperglycemia
|
|
|
The use of medication or medical devices to prevent the formation of blood clots is known as _________________ .
|
thromboprophylaxis
|
|
|
Hospitalised patients and residents of nursing homes account for about _________ of all cases of VTE.
|
60%
|
|
|
The primary initiator of DIC is ________________ .
|
endothelial dysfunction
|
|
|
What percentage of patients with DIC will die from DIC?
|
10-50
|
|
|
Most (_________) high blood pressure is primary hypertension or essential
hypertension (cause unknown). |
90-95%
|
|
|
One of the Rome II criteria for establishing a diagnosis of Chronic Functional Constipation is ________________________
|
fewer than 3 defecations per week
|
|
|
Huntington disease:
|
a neurodegenerative genetic
disorder (autosomal dominant) that affects muscle coordination and leads to cognitive decline and dementia. |
|
|
Huntington disease:
|
Onset of symptoms: 30-50 y.o. Hypotonia, involuntary
fragmentary movements (chorea). Later, progressive dementia, memory loss, loss of executive functions, slow Thinking, apathy, disinhibition, irritability. |
|
|
Huntington disease:
|
Pathology: severe degeneration of basal ganglia especially the
caudate nucleus; also frontal lobe atrophy and loss of GABA activity with a relative excess of dopaminergic activity. |
|
|
Huntington disease:
|
No effective treatment
|
