How are terazosin and tamsulosin used to treat BPH? How are these two drugs different?
Answer
Both are α₁ antagoinsts, which relax smooth muscle.
However, terazosin is α₁ non-selective and also lowers BP (by action on α1B receptors)
Tamsulosin is α1A selective and therefore does not affect blood vessels - it is used in normotensive individuals, therefore.
Card 16
How do 5α-reductase inhibitors factor into the treatment of BPH?
Answer
1) Block conversion of testosterone to DHT
2) Results take months
3) Can prevent male-pattern baldness
4) Gynecomastia and sexual dysfunction are side effects
Card 17
3 risk factors for developing prostate adenocarcinoma?
Answer
1) Age
2) Race (black > white > asian)
3) Diet rich in saturated fats
Card 18
How is PSA used to screen for prostate cancer?
Answer
1) Normal serum PSA is 2.5 ng/dL before 49, 7.5 ng/dL age 70-79. PSA increases with age due to BPH
2) PSA > 10 ng/dL is worrisome and indicative of cancer
3) Decreased % free-PSA is suggestive of cancer; cancer makes bound PSA
Card 19
Describe the Gleason grading system for prostate adenocarcinoma:
Answer
*Based on architecture alone - NOT nuclear atypia.
1) Multiple regions biopsied/assessed
2) A score of 1-5 is assigned to each region and then added to make a score between 2-10
3) Higher score indicates a worse prognosis
Card 20
How do prostate cancer mets present (discuss biomarkers as well)?
Answer
Osteoblastic lesions in the spine and pelvis,
presenting with back pain and
elevated serum ALP, PSA, and prostatic acid phosphatase (PAP)
Card 21
How are localized vs. diffuse prostatic cancers treated?
Answer
Local disease is treated with a prostatectomy, advanced disease is treated with hormone suppression.
Card 22
Pituitary adenomas can be "functional" or "nonfunctional", which refers to their ability to produce hormone. Nonfunctional pituitary adenomas present with what 3 symptoms? What are these symptoms collectively called?
Answer
1) Bitemporal hemianopsia
2) Hypopituitarism
3) Headache
Collectively, these consititue the tumor's "mass effect"
*Note: compression of the pituitary stalk by a non-functional adenoma may also produce gallactorrhea, since dopaminergic regulation of prolactin can become compromised (dopamine inhibits prolactin release)
Card 23
What are 3 common functional pituitary adenomas? What are 3 rare adenomas?
Answer
1) Prolactinoma
2) Growth Hormone cell adenoma
3) ACTH cell adenoma
TSH cell, LH-producing, and FSH-producing are rare
Card 24
How does a prolactinoma present in males and in females? What is the treatment?
Answer
Males: Decreased libido and headache
Females: Galactorrhea and amenorrhea
Treatment is dopamine agonists (bromocriptine or cabergoline) - this suppresses prolactin production and shrinks the tumor.
Larger lesions may need to be surgically excised.
Card 25
How does a growth hormone cell adenoma present differently in adults vs. children?
Answer
In children - gigantism, increased linear bone growth
In adults - acromegaly
Card 26
What are 3 clinical features of acromegaly?
Answer
1) Enlarged bones of the hands, feet, jaw
2) Growth of visceral organs leading to dysfuntion (cardiac failure)
3) Enlarged tongue
Card 27
Why is secondary diabetes mellitus often present in acromegaly?
Answer
GH induces liver gluconeogenesis
Card 28
What are 3 diagnostic tests/modalities used to diagnose acromegaly?
Answer
1) Elevated serum GH
2) Elevated serum IGF-1
3) Lack of GH suppression by oral glucose
What syndrome do ACTH secreting pituitary tumors lead to?
Answer
Cushing syndrome
Card 31
How much of the pituitary parenchyma must be rendered nonfunctional before signs of hypopituitarism manifest?
Answer
> 75%
Card 32
3 causes of hypopituitarism?
Answer
1) Pituitary adenoma (in adults)
2) Craniopharyngioma (kids)
**can either impinge on pituitary or hemorrhage (pituitary apoplexy)
3) Sheehan syndrome (postpartum hypopituitarism)
Card 33
Describe the pathogenesis of Sheehan syndrome:
Answer
Sheehan syndrome is a pregnancy-related infarction of the pituitary gland.
Gland doubles in size during pregnacy, blood supply does not increase accordingly. Blood loss during childbirth (parturition) precipitates an infarction.
Card 34
How does Sheehan syndrome present (3 symptoms)?
Answer
1) Poor lactation
2) Loss of pubic hair (arise due to LH from anterior pituitary)
3) Fatigue
Card 35
What is empty sella syndrome and how does it arise?
Answer
Herniation of the arachnoid/CSF into the sella compresses and destroys the pituitary gland.
Card 36
What two hormones made by the hypothalamus are released by the posterior pituitary, and what are their functions?
Answer
1) ADH (from the supraoptic nucleus of the hypothalamus), which acts on the renal tubules and collecting ducts to promote free water retention
2) Oxytocin (from the paraventricular nucleus of the hypothalamus), which mediates uterine contraction during labor and release of breast milk (ejection of milk, vs. PRL: milk production) in lactating mothers
Card 37
Describe the major differences (2) between central diabetes insipidus and nephrogenic diabetes insipidus:
Answer
1) Central DI is due to an ADH deficiency, induced by a posterior pituitary pathology (e.g. trauma, tumor, etc.)
By contrast, nephrogenic DI is caused by an imparied renal response to ADH (caused by mutations or drugs).
2) Central DI responds to (and is treated with) desmopressin (an ADH analogue).
By contrast, nephrogenic DI does not respond to desmopressin.
Card 38
What are the 3 clinical features of central or nephrogenic diabetes insipidus?
Answer
1) Polyuria and polydipsia with life-threatening dehydration
2) Hypernatremia
3) Low urine osmolality and specific gravity
↓ ADH ⇒ ↑ CH2O, thus concentrating serum
Card 39
What are 3 causes of syndrome of inappropriate ADH secretion?
1) Hyponatremia and low serum osmolality (contrast to DI, which has hypernatremia and high serum osmolality)
2) Mental status changes and seizures - hyponatremia induces neuronal swelling/cerebral edema
Card 41
What are 2 treatments for SIADH?
Answer
1) Free water restriction
2) 1st line: V2 ADH receptor antagonists ("-vaptans"),
or 2nd line: demeclocycline (reduces response of collecting tubules to ADH)
Card 42
Anterior neck mass may be related to what benign thyroid pathology? What about a mass at the base of the tongue?
Answer
1) Thyroglossal duct cyst (failure of thyroglossal duct to involute)
2) Lingual thyroid (remnant of thyroid tissue on the tongue)
Card 43
What are 2 general physiologic consequences of hyperthyroidism and what causes them?
Answer
1) Increased basal metabolic rate (due to increased synthesis of Na⁺/K⁺ ATPase)
2) Increased sympathetic nervous sytem activity (due to increased expression of β₁-adrenergic receptors)
Card 44
3 key symptoms of hyperthyroidism?
Answer
1) Weight loss
2) Heat intolerance and sweating
3) Tachycardia with increased cardiac output
Card 45
What is the root cause of Graves' disease?
Answer
IgG directed towards the TSH receptor that stimulates activity.
*Note, this would be considered a type II noncytotoxic hypersensitivity
Card 46
In whom does Graves disease occur?
Answer
Typically in women of childbearing age (20-40), though the disease is by no means limited to this population.
Card 47
3 clinical features of Graves disease:
Answer
1) Hyperthyroidism
2) Diffuse goiter - constant TSH stiulation leads to thyroid hyperplasia and hypertrophy
3) Exophthalmos and pretibial myxedema
Card 48
Describe the pathogenesis of exophthalmos and pretibial myxedema in Graves disease:
Answer
1) Fibroblasts that lie behind the orbit and over the shin both classically express the TSH receptor
2) TSH activation leads to glycosaminoglycan (GAG) buildup
3) Continual inflammation and fibrosis induce symptoms
Card 49
Describe the histology specimen depicted. Diagnosis?
Answer
Irregular follicles with scalloped colloid and chronic inflammation. Graves disease.
Card 50
What are 4 laboratory findings in Graves disease?
Answer
1) Increased total and free T4
2) Decreased TSH (T3 increase downregulates TRH receptors, decreasing TSH release)
3) Hypocholesterolemia (effects of increased LDL receptor expression predominate)
4) Increased serum glucose (upregulation of β₁-adrenergic receptors induces gluconeogenesis)
Card 51
3 treatment modalities for Graves disease:
Answer
1) β-blockers
2) Thioamides (PTU and methimazole)
3) Radioiodine ablation
Card 52
What is thyroid storm and how does it present?
Answer
Complication of Graves disease precipitated by stress (surgery or childbirth).
Elevated catecholamines and massive hormone excess cause arrhythmias, hyperthermia, vomiting, hypovolemic shock.
Card 53
3 treatment modalities for thyroid storm?
Answer
1) Propylthiouracil (life-threatening) or methimazole (not life-threatening)
2) β-blockers
3) Glucocorticoids
PTU: block peripheral T4-T3 conversion
methimazole: longer duration, results in more rapid normalization of serum T3, less hepatotoxic
Card 54
How does PTU treat thyroid storm?
Answer
Inhibits the peroxidase-mediated oxidation, organification and coupling steps of thyroid hormone synthesis, as well as the peripheral conversion of T4 to T3.
Card 55
Multinodular goiter is caused by what?
Answer
Iodine deficiency
Pathophysiology:
low iodine ⇒ low T3/T4 ⇒ TSH increases to compensate ⇒ follicular cell hypertrophy/hyperplasia
Recurrent episodes result in irregular enlargement, i.e. multinodular goiter.
Card 56
What is the difference between a non-toxic (euthyroid) goiter and a toxic goiter?
Answer
A toxic goiter has become TSH-independent, leading to uncontrolled T4 release and hyperthyroidism.
Card 57
What is the difference between cretinism and myxedema? What are they both examples of?
Answer
Both are examples of hypothyroid pathology; cretinism occurs in neonates and infants, myxedema is seen in older children and adults.
1) Iodine deficiency
2) Hashimoto thyroiditis (most common in west)
3) Drug-induced (lithium)
4) surgical removal/radioablation of the thyroid (treatment of Graves)
Card 61
Clinical features of hypothyroidism?
Answer
1) Myxedema (GAGs in skin/soft tissue)
2) Weight gain
3) Mental activity slowed
4) Weakness
5) Cold intolerance (contrast to heat intolerance in hyperthyroid)
6) Bradycardia
7) Oligomenorrhea
8) Hypercholesterolemia
9) Constipation
Card 62
Hashimoto thyroiditis is associated with what HLA type?
Answer
HLA-DR5 (also DR3)
Card 63
Most common cause of hypothyroidism in developed nations?
Answer
Hashimoto
Card 64
What are 3 key clinical features of Hashimoto?
Initial presentation?
Lab values following progression?
Antibodies?
Answer
1) Initially presents as hyperthyroidism (follicles damaged, release thyroid hormone)
2) Progresses to hypothyroidism: ↓ T4, ↑ TSH
3) Anti-thyroglobulin and anti-thyroid peroxidase autoantibodies present
Card 65
What can be seen in this histopathological specimen taken from the thyroid? Diagnosis?
Answer
Chronic inflammation and Hurthle cells (bottom left: large pink cells surrounding follicle). This is Hashimoto thryoiditis.
Card 66
What malignancy does Hashimoto confer an increased risk for?
Answer
B-cell (marginal zone) lymphoma
Card 67
What is DeQuervain thyroiditis? How does it present? What is the natural course of the disease?
Answer
A granulomatous thyroiditis that presents following a viral infection.
Thyroid is tender, transient hyperthyroidism
Self-limited; only about 15% of cases progress to a hypothyroidism
Card 68
A patient presents with a nontender "hard as wood" thyroid gland - diagnosis?
Answer
Riedel fibrosing thyroiditis
Card 69
What causes riedel fibrosing thyroiditis? What condition can it clinically mimic?
Answer
Chronic inflammation with fibrosis.
Clinically mimics anaplastic carcinoma, but patients are younger and malignant cells are absent.
Card 70
Three basic principles of diagnosing/treating thyroid neoplasia:
Answer
1) Presents as a distinct, solitary nodule which is more likely to be benign than malignant.
2) Iodine radiotracer studies are useful for initial workup: low activity/uptake indicates neoplasm (in contrast to a "hot nodule" characteristic of multinodular goiter)
3) Biopsy performed by fine needle aspiration
Card 71
Diagnosis?
Answer
Follicular adenoma - a benign proliferation of follicles surrounded by a fibrous capsule
Card 72
What are the 4 types of thyroid carcinoma and which is most common?
What is the major risk factor for thyroid papillary carcinoma?
Answer
Exposure to ionizing radiation during childhood
Card 74
Describe the histopathology and diagnose:
Answer
Papillae lined by cells with clear "orphan annie eye" nuclei with nuclear grooves. This is papillary carcinoma of the thyorid.
CA defn: nuclear features, not papilary projections (i.e. psammoma)
Psammoma mnemonic:
papillary carcinoma of the thyroid,
serous cystadenocarcinoma of the ovary,
meningioma,
ₘₑₛₒₜₕₑₗᵢₒₘₐ
Card 75
What is this?
Answer
Psammoma body found in a papillary carcinoma
Card 76
What is the natural history and prognosis of a papillary carcinoma?
Answer
Often spreads to cervical lymph nodes. However, prognosis is excellent, with a 95% 10 year survival.
Card 77
How can follicular carcinoma of the thyroid be distinguished from follicular adenoma?
Answer
Follicular carcinoma of the thyroid invades through the fibrous capsule surrounding it, whereas the adenoma does not.
Card 78
What procedures are necessary for distinguishing between follicular carcinoma and follicular adenoma?
Answer
A fine needle aspiration cannot be used to differentiate between the two, since FNA cannot assess penetration through surrounding fibrous capsule. Therefore, the whole capsule must be examined to make the diagnosis.
Card 79
How does follicular carcinoma of the thyroid spread?
Answer
Hematogenously.
Remember, it is one of the 4 carcinomas that do this, along with hepatocellular, renal cell, choriocarcinoma
Card 80
In medullary carcinoma of the thyroid, what is the malignant cell?
Answer
Parafollicular C cells of the thyroid.
Card 81
Why do patients with medullary carcinoma of the thyroid become hypocalcemic?
Answer
C cells are the malignant cell in this cancer - they secrete calcitonin, which inhibits osteoclast resorption and increases renal calcium excretion.
*Note that calcitonin will also precipitate in the thyroid as amyloid protein, giving this tumor it's characteristic "amyloid background" on histology
Card 82
Medullary carcinoma of the thyroid is typical in patients with MEN 2A and 2B. What other cancers is each condition associated with?
Answer
2A: pheochromocytoma, parathyroid hyperplasia
2B: pheochromocytoma, ganglioneuromas of the oral mucosa
Card 83
In whom is the poorly-differentiated anaplastic carcinoma of the thyroid seen? What is the prognosis?
Answer
The elderly. Quickly invades local structures leading to dysphagia and respiratory symptoms, so the prognosis is poor.
Card 84
What cells in the parathyroid gland secrete PTH?
Answer
Chief cells
Card 85
What are the 3 actions of PTH?
Answer
1) Increases osteoclast activity to release Ca²⁺ and PO₄³⁻
2) Increases small bowel absorption of Ca²⁺ and PO₄³⁻ by activating vitamin D (↑ 1α-OHase activity)
3) Increases renal Ca²⁺ reabsorption (DCT), decreases renal PO₄³⁻ reabsorption (PCT)
Card 86
What is the effect of calcium on PTH?
Answer
Inhibits its release (negative feedback)
Card 87
What are 3 causes of primary hyperparathyroidism? What is the most common?
1) ↑ serum PTH
2) ↑ serum calcium
3) ↓ serum phosphate (free Ca²⁺ binds PO₄³⁻)
4) ↑ urinary cAMP
5) ↑ serum ALP (osteoblasts use alk phos to make alkaline environ for bone mineralization)
Card 90
What is the treatment for primary hyperparathyroidism?
Answer
Surgical resection of the affected gland
Card 91
How is secondary hyperparathyroidism distinguished from primary, and what is the most common cause?
Answer
Hypocalcemia due to a disease process extrinsic to the parathyroid gland (e.g. renal failure: ↑ [PO₄³⁻]ₚₗ & ↓1α-OHase)
drives excess production of PTH.
In primary hyperparathyroidism, an intrinsic parathyroid gland disorder causes excess PTH.
Card 92
Describe the pathogenesis of renally-induced secondary hyperparathyroidism:
Answer
1) Loss of renal function results in inability to adequate excrete phosphate
2) Increased serum phosphate binds to free calcium
3) Decreased free Ca²⁺ stimulates the parathyroid glands
4) Increased PTH leads to bone resorption
Card 93
What 4 lab values do you expect to see in secondary hyperparathyroidism?
How do insulin levels change throughout the natural history of DM 2?
Answer
Insulin levels initially increase (resistance) in response to decreased expression of insulin receptors.
With time, the beta cells become exhausted, and insulin levels drop.
Card 106
What are the 3 diagnostic glucose level cutoffs for diagnosing T2DM?
Answer
1) Random glucose measurement > 200 mg/dL
2) Fasting glucose measurement > 126 mg/dL
3) Glucose tolerance test measurement > 200 mg/dL two hours after glucose loading
Card 107
What is hyperosmolar non-ketotic coma?
Answer
High glucose in a type II diabetic (> 500 mg/dL) leads to life-threatening diuresis with hypotension and coma
*Ketones are notably absent, since low levels of circulating insulin are still present
Card 108
3 modalities of treating T2DM?
Answer
1) Weight loss and exercise
2) Antihyperglycemics (sulfonylureas and metformin)
3) Insulin (once beta cells have become exhausted)
Card 109
Non-enzymatic glycosylation of large vessels leads to what pathology?
Answer
Atherosclerosis
Card 110
Non-enzymatic glycosylation (in diabetics) of small vessels in the kidney leads to what pathologies?
Answer
1) Glomerulosclerosis (scarred kidneys with granular surface)
2) Glomerular hyperfiltration injury (caused by preferential involvement of the efferent arterioles)
Card 111
Kimmelstiel-Wilson nodules in the glomeruli is indicative of what pathology?
Answer
Glomerular hyperfiltration injury (the nodules are the acellular accumulations seen in the mesangium)
Card 112
Non-enzymatic glycosylation of hemoglobin gives us what diagnostic tool?
Answer
Hemoglobin A₁C testing
Card 113
What is the pathogenesis of neuropathy in patient with T2DM (2 modalities)?
Answer
1) Glucose freely enters Schwann cells, aldose reductase converts glucose to sorbitol, which causes osmotic damage.
2) Nonenzymatic glycosylation (NEG) of endoneural vasculature
Card 114
What are the 3 layers of the adrenal cortex, and what substances does each produce?
What do all hormones synthesized in the adrenal cortex have in common?
Answer
They are all derived from cholesterol
Card 116
What three symptoms does hyperaldosteronism usually present with? How do these symptoms arise?
Answer
1) HTN
2) Hypokalemia
3) Metabolic alkalosis
Aldosterone increases absorption of sodium and secretion of potassium in the distal tubule and collecting duct. Increased sodium results in water retention and HTN. Alpha-intercalated cells exchange H⁺ for K⁺ attempting to correct hypokalemia. Alkalosis results.
Card 117
Why is edema often absent, despite an expanded plasma volume, in hyperaldosteronism?
Answer
A phenomenon known as "aldosterone escape", whereby increased plasma volume results in a "pressure natriuresis" that forces some fluid loss/sodium loss.
Thus:
↑ ECF
↑ MAP
↔ [Na+]ₚₗ
Card 118
Primary hyperaldosteronism can have what 3 etiologies?
How are aldosterone and renin levels affected in primary hyperaldosteronism? How is primary hyperaldosteronism treated?
Answer
1) High aldosterone, low renin (increased renal perfusion pressure downregulates renin)
2) Treated with mineralcorticoid receptor antagonists - spironolactone or eplerenone. Adenomas usually resected.
Card 120
What lab tests can help distinguish primary from secondary hyperaldosteronism?
Answer
Primary: ↑ aldosterone, ↓ renin
Increased JGA perfusion due to excess aldosterone inhibits renin secretion
Secondary: ↑ aldosterone, ↑ renin
Overactivation of the renin-angiotensin system prompts aldosterone secretion, e.g. renal artery stenosis
Card 121
Familial hyperaldosteronism can rarely be due to _________, which is characterized by [dz mech] .
Answer
Glucocorticoid-remediable aldosteronism (GRA);
aberrant expression of aldosterone synthetase in the fasiculata (should normally only be found in the glomerulosa)
Card 122
Glucocorticoid-remediable aldosteronism presents with what symptoms, and in whom?
Answer
HTN,
(+/-) hypokalemia,
high aldosterone,
low renin;
in children
Card 123
How do we test for suspected glucocorticoid-remediable aldosteronism?
Answer
Responds to dexamethasone test; confirm with genetic testing
Card 124
What is Liddle syndrome? How does it become confused with hyperaldosteronism?
Answer
Liddle syndrome is caused by decreased degradation of sodium channels in the collecting tubules.
Subsequent sodium retention also results in HTN, hypokalemia, and metabolic alkalosis in young children - these symptoms exactly mimic familial hyperaldosteronism.
However, unlike hyperaldosteronism, aldosterone will be decreased, since the primary defect is at the level of the sodium channels.
Card 125
How is Liddle syndrome treated? What therapeutic does not work?
Answer
Treatment is postassium-sparing diuretics: amiloride or triamterene. These block tubular sodium channels.
Spironolactone is not effective.
Card 126
3 modalities for diagnosing Cushing syndrome?
Answer
1) 24-hour urine cortisol level
2) Late night salivary cortisol (increased)
3) Low-dose dexamethasone suppression test (negative result)
Card 127
Does low-dose dexamethasone suppress cortisol production in any type/cause of Cushing's syndrome?
Answer
No. Low-dose examethasone fails to suppress cortisol production in literally any cause of hypercortisolism you could possibly ever think of or come across.
Card 128
(High) plasma ACTH distinguishes ACTH dependent and independent causes of Cushing. How do these guide your clinical process?
Answer
1) If an ACTH-independent cause, do a CT to look for an adrenal lesion
2) If ACTH-dependent, do a high-dose dexamethosone test - if ACTH is suppressed, we likely have a pituitary adenoma. If it is not, the ACTH is likely being secreted ectopically from some other tumor.
^(Background:)
^(1.) no response to low-dose dexamethasone → must be some sort of Cushing's)
^(2a.) if serum ACTH normal → ACTH-independent)
^(2b.) if serum ACTH high → ACTH dependent)
^(3.) do appropriate next test as described above)
Card 129
What information can be learned from a high-dose dexamethasone test?
Answer
If ACTH production is suppressed, root cause is a pituitary adenoma.
If ACTH production is unchanged, there is a tumor ectopically secreting ACTH.
Card 130
Congenital Adrenal Hyperplasia (CAH) can be caused by a variety of enzyme defects along the mineralcorticoid/androgen synthesis pathway. However, all variants share a common clinical feature, which is:
Answer
High ACTH (lack neg feedback due to ↓ cortisol), leading to bilateral adrenal hyperplasia
Card 131
21-hydroxylase deficiency is the most common form of CAH (90% of cases). It is divided into what two types, with what clinical presentations? Why do these symptoms manifest?
Answer
Classic - presents in neonates with
hyponatremia (↓ aldo ⇒ ↓ ENaC in CD principal cells ⇒ salt-wasting),
hypotension (↓ cortisol ⇒ hotn; salt-wasting ⇒ hyposm contr ⇒ hypovolemia), and
hyperkalemia (↓ Na+/K+ exch in CD);
females have clitoral enlargment (possibly ambiguous genitalia)
Nonclassic - presents later in life with
precocious puberty in males and
hirsuitism with menstrual irregularity in females.
Lack of 21-OHase shunts steroidogenesis towards androgen production.
Card 132
How does 11-hydroxylase deficiency present?
Answer
Similar to 21-hydroxylase deficiency, however, weak mineralcorticouds (DOC) are increased.
Presents with mild hypertension and hypokalemia (contrast with hyperkalemia in 21-OHase deficiency); renin and aldosterone are low.
Card 133
How does 17-hydroxylase deficiency present?
Cortisol and androgen production increased or decreased?
Female and male presentation?
Weak mineralcorticoids increased or decreased?
BP and potassium?
Renin and aldosterone?
Answer
Decreased cortisol and androgen production. -
Leads to primary amenorrhea and lack of pubic hair in females; pseudohermaphroditism in males.
Weak mineralocorticoids (DOC) increased.
Hypertension and mild hypokalemia.
Renin and aldosterone are low. (effects of weaker mineralocorticoids suppress production)
Card 134
How do we screen for CAH?
Answer
17-hydroxyprogesterone levels
If increased, this is 21- or 11-hydroxylase deficiency
If decreased, 17-hydroxylase deficiency
Card 135
What is the treatment for CAH?
Answer
Glucocorticoids,
(+/-) mineralocorticoids (21-OHase deficiency),
(+/-) sex steroids (17-OHase deficiency)
Card 136
What is Waterhouse-Friedrichsen syndrome?
Answer
Acute onset of adrenal insufficiency, usually caused by hemorrhagic necrosis of the adrenal glands, which is typically caused by DIC in children with Neisseria meningitidis. The lack of cortisol exacerbates hypotension, leading to death
Card 137
Chronic adrenal insufficiency is called?
Answer
Addison's disease
Card 138
3 causes of Addison's?
Answer
Destruction of adrenals via
1) Autoimmunity (most common in West)
2) TB infection (developing world)
3) Malignancy (metastatic lung carcinoma)
Card 139
Why are people with Addison's hyperpigmented?
Answer
Extreme excess of ACTH production (no negative feedback) induces melanocytes.
Card 140
Adrenal medulla is derived from what embryonic tissue?
Answer
Neural-crest chromaffin cells
Card 141
What does the adrenal medulla make?
Answer
Catecholamines (epi and norepi)
Card 142
What is a pheochromocytoma and how is it diagnosed?
Answer
Tumor of the chromaffin cells of the adrenal medulla - diagnosed by increased serum metanephrines and increased urine metanephrines and vanillylmandelic acid (VMA).
Card 143
Describe the surgical technique for removing a pheochromocytoma:
Answer
Phenoxybenzamine (irrev α-blocker) followed by a β-blocker are administered preoperatively to prevent a hypertensive crisis. This is because catecholamines leak into the bloodstream during manipulation of the tumor during surgery.
Card 144
What is the "rule of 10s" for pheochromocytoma?
Answer
10% bilateral
10% familial
10% malignant
10% located outside the adrenal medulla
Card 145
What 4 genetic conditions predispose to pheochromocytoma?
Answer
1) MEN 2A
2) MEN 2B
3) von Hippel-Lindau disease (VHL)
4) neurofibromatosis type 1 (NF1)
Card 146
What drug can induce adult hypothyroidism?
Answer
Lithium
Card 147
What is the most common pathogen associated with acute mastitis? How does it gain entry to the breast?
Answer
S. aureus.
Acute mastitis is associated with breast feeding - fissures develop in the nipple allowing entry of the organism and subsequent inflammation or abscess formation.
Card 148
What breast pathology is associated with a green-brown nipple discharge in a multiparous postmenopausal woman? What will biopsy reveal?
Answer
Mammary duct ectasia. Inflammation with dilation (ectasia) of the subareolar ducts.
Biopsy reveals chronic inflammation with infiltration of plasma cells.
DDx:
Medullary breast carcinoma is less likely to present with discharge. While the cancer also has plasma cells, its histology will demonstrate syncytium-like sheets of large cells rather than fibrosis; nuclear atypia can also distinguish the two. Imaging will demonstrate a fluid-filled cyst (if unruptured) in mammary duct ectasia, and this will be absent in the cancer.
Card 149
What are "blue domed cysts" on gross breast tissue examination a typical feature of?
Answer
Benign fibrocystic change
Card 150
Apocrine metaplasia, ductal hyperplasia/sclerosing adenosis, atypical hyperplasia: what increased risk for carcinoma do each of these conditions confer?
Answer
Apocrine metaplasia: no increased risk.
Ductal hyperplasia and sclerosing adenosis (calcified): 2x increased risk.
Atypical hyperplasia: 5x increased risk.
Card 151
How can you distinguish a papillary breast carcinoma from an intraductal papilloma?
Answer
Both present as bloody nipple discharge.
However, on histology, an intraductal papilloma will still posess a periphery of both luminal and myoepithelial cells around its fibrovascular projections.
Papillary carcinoma, by contrast, is characterized by fibrovascular projections lined by epithelial cells without underlying myoepithelium.
Card 152
What two breast changes (pathologies) present with a bloody nipple discharge?
Answer
Intraductal papilloma and papillary carcinoma
Card 153
What is the most common breast tumor in premenopausal women? Does it confer an increased risk for cancer?
Answer
Fibroadenoma; benign - no inreased risk of carcinoma
Card 154
What breast pathology has "leaf-life" projections? Malignant potential?
Answer
Phyllodes tumor: essentially a fibroadenoma with overgrowth of the fibrous component; commonly seen in postmenopausal women. Can be malignant.
Card 155
A mass was detected on mammogram and the lesion biopsied. Histopathological specimen shown. Diagnosis?
Answer
Fat necrosis/giant cell reaction; benign
Card 156
Histological specimen shown is classic for what breast pathology?
Answer
Apocrine metaplasia of the breast
Card 157
What features can be seen in this histopathological specimen taken from a breast?
Histological specimen shown is classic for what breast pathology?
Answer
Fibroadenoma
DDx:
Phyllodes has increased stromal cellularity and overgrowth, giving rise to the typical leaflike architecture
Card 159
Histological specimen indicative of what breast pathology?
Answer
Phylloides tumor
Card 160
What is shown in this histopathological specimen taken from a breast biopsy?
Answer
Ductal carcinoma in situ: comedo type
Card 161
What is this in this histological specimen taken from the breast indicative of?
Answer
Paget's disease of the breast (carcinoma invading nipple epithelium)
Card 162
Breast biopsy returns this histological specimen. Diagnosis?
Answer
Invasive Lobular Carcinoma - note the "single file" pattern of cells
Memory Tips:
Invasive Lobular Carcinoma - linear, i.e. tumor cells grow in single file due to lack of E-cadherin
Ductal CIS - "direct risk," i.e. same breast at risk for cancer; LCIS has much higher risk of bilateral involvement
Card 163
What are the two epithelial layers of the breast lobules and ducts? What are their functions? `
Answer
Luminal layer - inner layer, produces milk
Myoepithelial layer - outer layer, contractile function propels milk to the nipple
Card 164
How does prepubescent breast tissue differ from post?
Answer
Before puberty, both male and female breast tissue consists primarily of large ducts under the nipple. After puberty in females, lobules and small ducts form.
Card 165
Where are the majority of lobules and small ducts found in the female breast?
Answer
Highest density is in the upper outer quadrant.
Card 166
What is galactorrhea and what are 3 causes?
Answer
Defined as (inappropriate) milk production outside of lactation.
Causes include: nipple stimulation, prolactinoma of the anterior pituitary, and drugs (risperidone)
Card 167
What is periductal mastitis and in whom is it most commonly seen?
Answer
Inflammation of the subareolar ducts - most often seen in smokers.
cigar-shaped calcifications--you are what you... smoke?
Card 168
Why do smokers develop periductal mastitis?
Answer
Relative vitamin A deficiency results in squamous metaplasia of the lactiferous ducts, producing blockage and inflammation.
Card 169
How does periductal mastitis typically present? What does this clinical presenation mimic?
Answer
Subareolar mass with nipple retraction; mimics breast cancer (before jumping to conclusions, consider the history)
Myofibroblasts in granulation tissue (due to fibrosis) pull in skin
Card 170
What is the most common change seen in postmenopausal breast?
Answer
Fibrocystic change
Card 171
Fibrocystic changes most typically present in what area of the breast?
Answer
Upper outer quadrant
Card 172
How does a fibroadenoma present?
Answer
A well-circumscribed, mobile, marble-like mass.
Estrogen sensitive: grows during pregnancy, painful during menstruation.
Card 173
What are the 6 risk factors for developing breast carcinoma (any type)?
Answer
1) Female
2) Age
3) Early menarche/late menopause
4) Obesity
5) Atypical hyperplasia
6) First-degree relative with cancer
*Note, most of these have to do with estrogen exposure
Card 174
Does ductal carcinoma in situ invade the basement membrane?
Answer
DCIS does not involve the basement membrane
Card 175
How is DCIS usually detected?
Answer
Often seen as calcification of the ducts on mammography - usually does not produce a mass
Card 176
Mammographic calcifications as would be seen in instances of DCIS are fairly indistinguishable from what other 2 benign pathologies? What is necessary for accurate diagnosis?
Answer
Calcification resembles fibrocystic changes (sclerosing adenosis) and fat necrosis.
Biopsy of the calcifications is necessary for diagnosing malignant conditions.
Card 177
How is the "comedo-type" of DCIS histologically characterized?
Answer
High grade cells with necrosis and dystrophic calcification in the center of ducts.
Card 178
What is Paget's disease of the nipple, and how does it present?
Answer
DCIS that extends up the ducts to involve the skin of the nipple.
Presents with ulceration and erythema of the nipple
Card 179
Breast malignancy that classically forms duct-like structures?
Answer
Invasive ductal carcinoma. Most common invasive carcinoma of the breast (80% of cases)
Card 180
How large must a mass caused by an invasive ductal carcinoma be for simple clinical detection? How about by mammography?
Answer
1) 2 cm
2) 1 cm
Card 181
Dimpling of the skin and retraction of the nipple might be a sign of what underlying malignancy?
Answer
Invasive ductal carcinoma (peau d’orange most commonly seen in inflammatory carcinoma)
Card 182
Biopsy of invasive ductal carcinoma generally reveals duct-like structures in a desmoplastic stroma. There are 4 special subtypes - what are they?
Answer
The 4 subtypes of invasive ductal carcinoma are:
1) Tubular carcinoma
2) Mucinous carcinoma
3) Medullary carcinoma
4) Inflammatory carcinoma
Card 183
Tubular carcinoma: histology and prognosis?
Answer
Well differentiated tubules lacking myoepithelial cells; decent prognosis
Card 184
Mucinous carcinoma of the breast: histology and prognosis?
Answer
Carcinoma with abundant extracellular mucin; decent prognosis
DDx:
tubular carcinoma (tubules sans myoepithelial cells), also good prognosis
Card 185
Average age of mucinous breast carcinoma patient?
Answer
Average age is 40 years
Card 186
Medullary breast carcinoma: histology and prognosis?
Answer
Large, high grade cells growing in sheets with associated lymphocytes and plasma cells; decent prognosis
Card 187
What benign condition can medullary carcinoma of the breast mimic on mammography?
Answer
Fibroadenoma
Card 188
BRCA1 carriers have an increased risk of developing what subtype of invasive ductal carcinoma?
Answer
Medullary carcinoma
Card 189
Inflammatory carcinoma - where is the tumor invading?
Answer
Inflammatory carcinoma invades the dermal lymphatics
Card 190
What is the presentation and prognosis of inflammatory carcinoma?
Answer
Presents as an inflamed, swollen breast that closely mimics acute mastitis.
Poor prognosis
Card 191
Breast malignancy that characteristically grows in a single-file pattern and can show signet-ring morphology?
Answer
Invasive lobular carcinoma
Memory Tips:
Invasive Lobular Carcinoma - linear, i.e. tumor cells grow in single file due to lack of E-cadherin
Ductal CIS - "direct risk," i.e. same breast at risk for cancer; LCIS has much higher risk of bilateral involvement
Card 192
Why doesn't invasive lobular carcinoma form tubules?
Answer
Lacks E-cadherin
Memory Tips:
Invasive Lobular Carcinoma - linear, i.e. tumor cells grow in single file due to lack of E-cadherin
Ductal CIS - "direct risk," i.e. same breast at risk for cancer; LCIS has much higher risk of bilateral involvement
Card 193
What is the most important prognostic factor in breast cancer? What is the most useful prognostic factor?
Answer
1) Metastasis is the most important prognostic factor, however, most patients present before metastasis occurs
2) Spread to axillary lymph nodes is therefore the most useful factor
Card 194
What three predictive factors best predict response to treatment in breast cancer?
Presence of ER and PR in breast cancer indicates what type of treatment approach? Where are these receptors located?
Answer
Use antiestrogenic agents - tamoxifen.
Both receptors located in the nucleus (these are steroid hormone receptors)
Card 196
How does HER2/neu amplification in breast cancer direct your treatment? Where is this therapeutic target located?
Answer
Use trastuzumab (Herceptin).
HER2/neu is a growth factor receptor located on the cell surface.
Card 197
"Triple-negative" breast cancers, which lack ER, PR, and HER2/neu, have a poor prognosis and are more commonly seen in whom?
Answer
African-american women
Card 198
What % of breast cancer cases are related to hereditary factors?
Answer
10%
Card 199
What gene mutation is associated with male breast cancer development?
Answer
BRCA2
Card 200
Why is there still a risk of cancer development in patients who have undergone elective bilateral mastectomy?
Answer
Breast tissue can sometimes extend into the axilla or subcutaneous tissue of the chest wall.
Card 201
What percentage of all breast cancers are male breast cancers?
Answer
1%
Card 202
How does male breast cancer present?
Answer
A subareolar mass in older males that may produce a nipple discharge (densest area of breast tissue in males is subareolar)
*A good concept to illustrate here is that breast cancer tends to arise in the area of densest breast tissue - in women this is the upper outer quadrant
Card 203
What is the most common histological subtype of male breast cancer?
Answer
Invasive ductal carcinoma
Male breasts develop ducts without lobules
Card 204
What genetic condition other than BRCA2 mutation is male breast cancer associated with?
Answer
Klinefelter syndrome (47,XXY)
Card 205
What are the 3 general components of the neural tube, and what structures do they form?
Answer
1) Wall of the neural tube: forms CNS tissue
2) Lumen of the neural tube: forms ventricles and spinal cord canal
3) Neural crest: forms peripheral nervous system
Card 206
Deficiency of what vitamin is associated with neural tube defects?
Answer
Folate
Card 207
A fetus is delivered with a 'frog-like' appearance. The mother had polyhydramnios during gestation. Diagnosis?
Answer
Anencephaly.
Absence of brain → absence of swallowing reflex → polyhydramnios.
Card 208
What are the key differences/findings between spina bifida occulta, meningocele, and myelomeningocele?
Answer
1) Spina bifida: vertebral defect - no herniation of meninges or spinal cord, patch of hair overlies the defect
2) Meningocele: spinal defect with protrusion of the meninges
3) Myelomeningocele: spinal defect with protrusion of the meninges and spinal cord
Card 209
What is the most common cause of hydrocephalus in a newborn?
Answer
Cerebral aqueduct stenosis.
Noncommunicating Hydrocephalus Pathophysiology:
Obstruction in ventricles (e.g. aqueductal stenosis) impedes CSF absorption. Compare this to:
communicating - obstruction in subarachnoid space
normal pressure - CSF not absorbed by arachnoid villi (e.g. posttraumatic meningeal hemorrhage)
ex vacuo - ventricular enlargement secondary to reduced brain volume (e.g. caudate nucleus degen)
pseudotumor cerebri - increased ICP due to resistance to CSF outflow at arachnoid villi
Card 210
Describe the pathway of CSF from secretion to the subarachnoid space:
Answer
1) CSF produced by the choroid plexus lining ventricles
2) Flows from lateral ventricles to 3rd ventricle via interventricular foramen of Monro
3) Flows from 3rd ventricle to 4th ventricle via the cerebral aqueduct
4) Flows from 4th ventricle to subarachnoid space via foramina of Magendie (medial) and Luschka (lateral)
Card 211
Describe a Dandy-Walker malformation:
Answer
1) Congenital failure of cerebellar vermis to develop
2) Presents as massively dilated 4th ventricle with "absent" cerebellum on imaging
Card 212
Describe an Arnold-Chiari Type II malformation (3 features):
Answer
1) Congenital downward displacement of cerebellar vermis and tonsils through the foramen magnum
2) Obstruction of CSF flow commonly leads to hydrocephalus
3) Often associated with myelomeningocele
Card 213
What are 2 causes of syringomyelia?
Answer
Arises with trauma or in association with Arnold-Chiari type I malformation
Card 214
What spinal roots are commonly associated with syringomyelia?
Answer
C8-T1
Card 215
What is the pattern of sensory loss in syringomyelia? Why this pattern?
Answer
Pain and temperature are lost in a "cape-like" distribution, but fine touch and proprioception remain intact.
This is because the anterior white commissure of the spinothalamic tract is involved, but the dorsal columns are spared.
Card 216
If a syrinx goes untreated and continues to expand, what 2 parts of the spinal cord may become involved? What symptoms would manifest clinically?
Answer
1) Lower motor neurons of the anterior horn: muscle atrophy, weakness, impaired reflexes
2) Lateral horn of the hypothalamospinal tract: Horner syndrome
Card 217
What part of the spinal cord becomes damaged in poliomyelitis? What symptoms result?
Answer
1) The anterior motor horn becomes damaged
2) LMN signs manifest, specifically:
- flaccid paralysis with muscle atrophy
- fasciculations: spont LMN depol leads to synchronous contraction of skel mm fibers in a single motor unit
- impaired reflexes
*Remember that LMN lesions present without Babinski
Card 218
What is Werdnig-Hoffman disease (don't forget to mention mode of inheritence)?
Answer
An inherited autosomal recessive condition that results in degeneration of the anterior motor horn.
Presents as "floppy baby". Death occurs within a few years.
Card 219
What spinal tracts are affected in amyotrophic lateral sclerosis? What symptoms ensue?
Answer
Anterior motor horn: lower motor neuron signs, such as flaccid paralysis, fasciculations, impaired reflexes, etc.
Lateral corticospinal tract: upper motor neuron signs, such as spastic paralysis, hyperreflexia, increased muscle tone, and presence of Babinski.
Card 220
What is an early sign of Amyotrophic Lateral Sclerosis?
Answer
Atrophy and weakness of the hands
Card 221
Though most cases of Amyotrophic Lateral Sclerosis are sporadic, a mutation in what enzyme is associated with familial cases?
Answer
Mutation in the zinc-copper superoxide dismutase (SOD1). Leads to free radical injury in neurons.
Card 222
What is the the mode/mechanism of inheritence of Friedreich Ataxia? What gene/chromosome is affected?
Answer
Autosomal recessive; GAA trinucleotide expansion of the frataxin gene on chromosome 9
Card 223
How does a mutation in the Frataxin gene result in pathology?
Answer
Frataxin is essential for mitochondrial regulation of iron. Loss/dysfuntion of the protein results in iron buildup and free radical damage to the mitochondria
Card 224
3 clinical features of Friedreich's Ataxia?
Answer
1) Cerebellar degeneration - causes ataxia
2) Degeneration of multiple spinal cord tracts - loss of vibratory sense, loss of proprioception, muscle weakness (particularly in the LE), loss of DTR
3) Hypertrophic cardiomyopathy
Pathophysiology:
Frataxin loss results in mitochondrial (ETC) dysfunction; highly aerobic tissues (neurons, cardiomyocytes) affected first
Card 225
Where are the 1st, 2nd, and 3rd order neurons in the spinothalamic tract?
Answer
1) Peripheral nerves → posterior horn
2) Posterior horn → thalamus (decussates in the anterior white commissure at the level it enters)
3) Thalamus → cortex
Card 226
Where are the 1st, 2nd, and 3rd order neurons in the dorsal column-medial lemniscus (DC-ML) pathway?
Where are the 1st, 2nd, and 3rd order neurons in the lateral corticospinal tract?
Answer
1) Pyramidal neurons in the cortex descend, cross over in medullary pyramids → appropriate synapse on anterior motor horn
2) Anterior motor horn → muscle
3) There is no third order neuron in this pathway. Gotcha!
Card 228
Where are the 1st, 2nd, and 3rd order neurons in the hypothalamospinal tract (sympathetic input to the face)?
Answer
1) Hypothalamus → lateral horn at T1 level
2) Lateral horn at T1 → sympathetic superior cervical ganglion
3) Superior cervical ganglion → eyelids, pupil, face
Card 229
What are the "leptomeninges"?
Answer
Refers to the pia and arachnoid (light & thin)
Card 230
3 most common causes of meningitis in neonates:
Answer
1) Strep agalactiae (Group B strep)
2) E. coli
3) Listeria
Card 231
Most common cause of bacterial meningitis in:
1) Kids and teens
2) Adults/the elderly
3) Unvaccinated infants
Answer
1) N. meningitidis
2) Strep pneumo
3) H. flu
Card 232
Most common cause of viral meningitis?
Answer
Coxsackie virus
Card 233
Classic triad of meningitis?
Answer
1) Fever
2) Headache
3) Nuchal rigidity
Photophobia may or may not be present
What are 4 general etiologies of global cerebral ischemia?
Answer
1) Low perfusion - local (e.g. atherosclerotic disease of cerebral vasculature)
2) Acute decrease in blood flow - systemic (e.g. cardiogenic shock)
3) Chronic hypoxia - no O₂ (e.g. anemia)
4) Repeated episodes of hypoglycemia - no glucose (e.g. insulinoma)
Card 238
Survival of severe global ischemia with diffuse necrosis leads to what?
Answer
Vegetative state
Card 239
What are the 3 regions of the CNS that are highly susceptible to ischemic injury during a global cerebral ischemic event?
Answer
1) Pyramidal neurons of the cerebral cortex - layers 3,5,6
2) Pyramidal neurons of the hippocampus (CA5, 'Somner's sector')
3) Purkinje layer of the cerebellum
^((Note that these are same cells affected by rhabdovirus. Bungee sounds like Purkinje, hence bungees in tree.))
Card 240
What is the difference between a stroke and a transient ischemic attack (TIA)?
Answer
Same symptoms, but if symptoms resolve within 24 hours, it is deemed a TIA
Card 241
What are 3 subtypes of ischemic strokes?
Answer
1) Thrombotic - plaque rupture from circle of Willis
2) Embolic - hemorrhagic (reperfusion) infarct risk, e.g. afib embolus lodges & lyses
3) Lacunar - hylaine arterioloscl due to htn
Card 242
Describe the pathogenesis of a thrombotic stroke. What part of the brain is usually affected?
Answer
Thrombotic strokes are due to rupture of atherosclerotic plaques, which usually develop at branch points within the circle of Willis.
Thrombotic strokes usually result in pale infarcts at the periphery of the cortex.
Card 243
Describe the pathogensis of an embolic stroke. What kind of stroke is the typical result? What part of the brain is affected?
Answer
Embolic strokes are caused by thromboemboli which most commonly arise in the left side of the heart (atrial fibrillation).
They most commonly involve the MCA, and result in a hemorrhagic infarct at the periphery of the cortex.
Card 244
Describe the pathogenesis of a lacunar stroke:
Answer
Occurs secondary to hyaline arteriolosclerosis (consequence of HTN). Most commonly involves the lenticulostriate arteries, resulting in small cystic areas of infarction.
Card 245
In what instances do lacunar strokes manifest as pure motor or pure sensory strokes?
Answer
1) Involvement of internal capsule only yields a pure motor stroke
2) Involvement of the thalamus only yields a pure sensory stroke
Card 246
What changes do you expect to see post-ischemic stroke at:
12 hours?
24 hours?
1-3 days?
4-7 days?
2-3 weeks?
What is the most common cause of intracerebral hemorrhage?
Answer
Rupture of Charcot-Bouchard microaneurysms of the lenticulostriate vessels.
Card 248
What is the most common site of intracerebral hemorrhage?
Answer
The basal ganglia
Card 249
What is the most common cause of subarachnoid hemorrhage?
Answer
Rupture of a berry aneurysm
Card 250
3 clinical features of subarachnoid hemorrhage?
Answer
1) Thunderclap headache - "worst headache, 10/10 would not do again"
2) Nuchal rigidity - irritation of meninges (esp arachnoid/pia)
3) Xanthochromia on CSF aspiration
Card 251
What is a berry aneurysm?
Answer
A saccular outpouching of the cerebral vasculature that lacks a media. Most commonly occurs at the branch point between the anterior cerebral arteries and the anterior communicating artery.
Card 252
Berry aneurysms are associated with what two genetic disorders?
What structures are typically damaged in an epidural hematoma?
Answer
Typically caused by a fractured temporal bone with rupture of the middle meningeal artery.
Card 255
How does an epidural hematoma appear on imaging? How does it differ from a subdural hematoma?
Answer
Lens shaped lesion, does not cross sutures (dura tightly adheres to the adjacent skull at suture lines).
Card 256
What structures are usually damaged to cause a subdural hematoma?
Answer
The bridging veins that lie between the dura and arachnoid.
Incidence is higher in the elderly due to age-related cerebral atrophy, which stretches the veins
Card 257
Who is at increased risk for subdural bleeds and why?
Answer
The elderly; age related cerebral atrophy stretches the bridging veins
Card 258
How does a subdural hemorrhage appear on CT? How does it differ from an epidural hematoma?
Answer
Crescent shaped lesion that can cross the sutures
(but not dural reflections, e.g. falx cerebri, tentorium cerebelli, falx cerebelli).
Card 259
Describe a tonsillar herniation and associated complications:
Answer
Cerebellar tonsils herniate through the foramen magnum. Compression of the brain stem leads to cardiopulmonary arrest.
Card 260
Describe a subfalcine herniation and associated complication:
Answer
Displacement of the cingulate gyrus underneath the falx.
Compression of the anterior cerebral artery leads to infarction.
Card 261
Decribe an uncal herniation. What are the 3 main consequences of such a herniation?
Answer
Displacement of the temporal lobe uncus under the tentorium.
1) Compression of CN III
2) Compression of the PCA leads to infarction of the occiptal lobe and contralateral homonymous hemianopsia
3) Rupture of paramedian artery leads to Duret (brainstem) hemorrhage
Card 262
What are the 3 leukodystrophies and what causes each? What are their respective inheritance patterns?
Answer
1) Metachromatic leukodystrophy: AR deficiency in arylsulfatase - sulfatides cannot be broken down and accumulate in the lysozomes of oligodendrocytes.
2) Krabbe disease: AR deficiency of galactocerebrosidase
3) Adrenoleukodystrophy: X-linked defect in the addition of CoA to long-chain fatty acids. Results in damage to both adrenals and white matter of the brain
Card 263
What HLA type is multiple sclerosis associated with?
Answer
HLA-DR2
Card 264
What geographical regions is MS more commonly seen in?
Answer
Incidence of MS seems to correspond with distance from the equator (i.e. Santa has MS)
Card 265
Lesions due to MS in the following locations will cause what symptoms?
Optic nerve:
Brainstem:
Medial longitudinal fasiculus:
Periventricular white matter:
Spinal cord:
Autonomic nervous system:
Answer
1) optic nerve: unilat blurred vision
2) brainstem: vertigo and scanning speech (like EtOH intox)
3) MLF: internuclear ophthalmoplegia
4) periventricular white matter: hemiparesis/sensation loss
5) spinal cord: LE loss of sensation
6) ANS: bowel, bladder, sexual dysfunction
Card 266
By what two modalities is the diagnosis of MS made? What results do you expect to see?
Answer
1) MRI reveals plaques
2) Lumbar puncture shows lymphocytes, immunoglobulins with oligoclonal IgG bands, and myelin basic protein
Card 267
How is MS acutely and chronically treated?
Answer
1) High-dose steroids for acute attacks
2) IFN-β slows progression of disease (long-term treatment)
Card 268
What causes progressive multifocal leukoencephalopathy?
Answer
JC virus infection of the oligodendrocytes in the context of immunosuppression (AIDS, transplant, leukemia). Most people harbor JC virus.
Card 269
Subacute sclerosing panencephalitis (SSPE) has what etiology? What will histologic examination of the brain reveal?
Answer
Caused by measles - infection usually occurs in infancy, SSPE manifests years later
Viral inclusions in neurons and oligodendrocytes (hence demyelination and atrophy) can be seen on histology.
Card 270
What causes central pontine myelinolysis and how does it typically present?
Answer
Results from (typically iatrogenic) overly-rapid correction of hyponatremia. Manifests as 'locked-in' syndrome.
"from low to high, your pons will die"
Card 271
5 clinical features of Alzheimer disease:
Answer
1) Slow-onset memory loss (short-term first, progresses to long-term)
2) Loss of learned motor skills and language
3) Changes in behavior and personality
4) Patients become mute and bedridden
5) Infection is most common cause of death
Card 272
What two factors contribute to risk of developing Alzheimer's?
Answer
1) Age: risk doubles every 5 years after the age of 60
2) APO-E allele: ϵ4 is associated with increased risk, ϵ2 with decreased risk
Memory Tip:
"4 > 2, and risk(ϵ4) > risk(ϵ2)"
Card 273
Early-onset Alzheimer's is seen in what two instances?
Answer
1) Familial cases - presenilin 1 and 2 mutations
2) Down sydrome - patients develop symptoms by 40 years of age
*reminder: amyloid precursor protein (APP) is found on chromosome 21
Card 274
What are the 4 morphologic features of Alzheimer's?
Answer
1) Cerebral atrophy with narrowed gyri (and widened sulci; via hydrocephalus ex vacuo)
2) Neuritic plaques composed of Aβ amyloid
3) Neurofibrillary tangles composed of tau protein ("tau for τangles")
4) Loss of cholinergic neurons in the nucleus basalis of Meynert
Hydrocephalus Ex Vacuo Pathophysiology:
Ventricular enlargement secondary to reduced brain volume. Compare this to:
noncommunicating - obstruction in ventricles (e.g. aqueductal stenosis)
communicating - obstruction in subarachnoid space
normal pressure - CSF not absorbed by arachnoid villi (e.g. posttraumatic meningeal hemorrhage)
pseudotumor cerebri - increased ICP due to resistance to CSF outflow at arachnoid villi
Card 275
Where does Aβ amyloid come from? On which chromosome is its gene?
Answer
It is derived from amyloid precursor protein (APP) which is found on chromosome 21
(possibly related to why Down syndrome patients are at higher risk for developing Alzheimer's).
APP normally undergoes alpha cleavage.
Beta cleavage yields the pathologic amyloid protein.
Card 276
Why is there an increased risk of cerebral hemorrhage in Alzheimer's?
Answer
Amyloid protein can deposit around cerebral vasculature, stiffening and weakening it
Card 277
What is tau protein?
Answer
It is a microtubule-associated protein
Card 278
How is Alzheimer's diagnosed?
Answer
Presumptive diagnosis made clinically; diagnosis of exclusion.
Confirmed by histology on autopsy.
Card 279
What is vascular dementia? What causes it?
Answer
Dementia related to multifocal infarction caused by HTN, atherosclerosis, or vasculitis. Result of moderate global cerebral ischemia. 2nd most common cause of dementia.
Card 280
What is Pick disease? What is the defining histological structure?
Answer
Degenerative disease of the frontal and temporal cortex (it is one type of frontotemporal dementia).
Defined by Pick bodies, which are round aggregates of tau protein.
Card 281
What causes Parkinson's disease?
Answer
Loss of dopaminergic neurons in the substantia nigra pars compacta.
Card 282
What are the 4 general clinical features of Parkinson's?
Answer
TRAP:
Tremor - pill-rolling motion, occurs at rest ("resting tremor")
Rigidity - cogwheel rigidity of limbs/trunk
Akinesia/Bradykinesia - slowness to/lack of movement
Postural instability/shuffling gait
Card 283
What are Lewy bodies composed of? What conditions would they be seen in?
Answer
Lewy bodies are composed of α-synuclein.
Seen in Parkinson's (late onset dementia) and Lewy Body Dementia (early onset dementia).
Card 284
What is the cause of Huntington's disease?
Answer
CAG trinucleotide expansion in the huntingtin gene on chromosome 4.
Huntingtin gain-of-function leads to aggregation, but nobody knows if that causes the disease or if it's an effect of an underlying process. Atrophy of the caudate nucleus is observed grossly, and striatal damage results in release of inhibition, resulting in chorea (quick, continuous, and uncontrollable movements).
Card 285
What are 3 clinical symptoms of Huntington's?
Answer
1) Chorea (~) - striatal damage releases movement inhibition (i.e. "don't hold back, dance!")
2) Depression :(
3) Dementia (?)
Card 286
What is the average age of presentation for Huntington's?
Answer
40 years
Number of CAG repeats and age of onset are inversely related (More CAG → die younger).
Repeat expansions occur during spermatogenesis, so that paternal transmission (dz is autosomal dominant) is associated with anticipation. There is no sporadic form of HD.
Examples:
1.) Dad (hh) + Mom (Hh) had a kid (Hh). Dad is healthy, so no repeat expansions from him. Kid lives as long as Mom.
2.) Dad (Hh) + Mom (hh) had a kid (Hh). Dad has disease, so his sperm has more CAGs than his somatic cells. Kid dies sooner than Dad.
Card 287
What is the triad of symptoms seen in normal pressure hydrocephalus?
Answer
Urinary incontinence
Gait instability (magnetic gait)
Dementia
"Wet, Wobbly, and Wacky"
Normal Pressure Hydrocephalus (NPH) Pathophysiology:
CSF is not absorbed by arachnoid villi, e.g. secondary to posttraumatic meningeal hemorrhage. Mild pressure buildup (unnoticeable on spinal tap) damages motor areas of frontal lobe/periventricular white matter tracts. Compare this to:
noncommunicating - obstruction in ventricles (e.g. aqueductal stenosis)
communicating - obstruction in subarachnoid space (includes NPH)
ex vacuo - ventricular enlargement secondary to reduced brain volume (e.g. caudate nucleus degen)
pseudotumor cerebri - increased ICP due to resistance to CSF outflow at arachnoid villi
Card 288
Describe the pathogeneis of prion diseases:
Answer
1) Prion protein is normally expressed in CNS neurons in an α-helical conformation (PrPᶜ).
2) Disease arises upon exposure to β-pleated conformation (PrPˢᶜ).
Card 289
What are 3 ways in which Creutzfeldt-Jakob Disease (CJD) (not variant CJD) can arise?
Answer
1) Sporadically
2) Exposure to prion-infected human tissue via:
- Human growth hormone use
- Corneal transplant
Card 290
How does variant CJD transmit?
Answer
From exposure to bovine spongiform encephalopathy ('mad cow disease')
Card 291
What is fatal familial insomnia?
Answer
An inheritied prion disease characterized by severe insomnia and exaggerated startle response
Card 292
What percentage of brain tumors are primary? What percentage represent metastasis?
Answer
50%; 50%
Card 293
What three tumors most commonly metastasize to the brain?
Answer
1) Lung ^([large cell]) - adrenal (>50%), liver (40%), brain (20%), bone (20%)
2) Breast - bone (40-80%), viscera (25-35%), brain (10-30%)
3) Kidney - mets to lungs (>50%), bones (33%), regional lymph nodes, liver, adrenal, brain
*Melanoma is also a big one, and important to know
Card 294
Anatomically, where do adult brain tumors typically arise? What about pediatric tumors?
A man is diagnosed with a malignant tumor of astrocytes. MRI reveals a tumor that crosses the corpus callosum ('butterfly lesion'). What is the likely malignancy? What will histology of the tumor reveal?
Answer
Glioblastoma multiforme.
Histology will reveal regions of necrosis with GFAP(+) pseudopallisading tumor cells
Card 298
A woman presents to clinic with seizures. Imaging reveals a round mass attached to the dura. What tumor is this? What cell type does it arise from? What will be seen on histology?
Answer
This is a meningioma.
Arises from arachnoid cells.
Histology reveals a whorled pattern (+/-) psammoma bodies.
Psammoma mnemonic:
papillary carcinoma of the thyroid,
serous cystadenocarcinoma of the ovary,
meningioma,
ₘₑₛₒₜₕₑₗᵢₒₘₐ
Card 299
A woman comes in with hearing loss and vertigo. Imaging revelas a mass at the cerebellopontine angle. What biomarker will this tumor stain positive for?
Answer
This is a schwannoma, which will be S-100(+).
*To review, melanoma and langerhans cell histiocytosis are the other S-100(+) malignancies
Card 300
Bilateral acoustic schwannomas are characteristic of what inherited condition?
Answer
Neurofibromatosis 2
Memory Tip:
"2" for bilateral
Card 301
A man presents with seizures. Imaging revelas a calcified tumor in the white matter of the frontal lobe. What tumor? What will be seen on histology?
Answer
Oligodendroglioma. Fried egg (myelin loss) appearance on histology.
Card 302
A child presents with cerebellar symptoms. Imaging reveals a cystic lesion with a mural nodule. What is the diagnosis? What 3 unique histological features will be seen?
Answer
This is a pilocytic astrocytoma.
Biopsy reveals:
1) Rosenthal fibers (thick eosinophilic astrocyte processes)
2) Eosinophilic granular bodies
3) Tumor cells are GFAP(+)
Card 303
What is the malignant cell in a medulloblastoma?
Answer
Medulloblastoma arises from granular cells of the cerebellum (neuroectoderm)
Card 304
What does histological examination of a medulloblastoma reveal (2 features)?
Answer
1) Small, round, blue cells
2) Homer-Wright rosettes
Card 305
What does the term "drop metastasis" refer to?
Answer
Metastasis of a primary brain tumor to the cauda equina. Almost entirely seen in cases of medulloblastoma.
Card 306
A child presents with symptoms of hydrocephalus. A mass is found to be obstructing the 4th ventricle. What is this tumor? What is the characteristic histological finding?
Answer
This is an ependymoma - 4th ventricle is the most common location.
Perivascular pseudorosettes are seen on histological examination.
Card 307
A child presents with bitemporal hemianopsia. A mass is found to be compressing the optic chiasm. The mass possesses tooth-like calcifications. What is this mass? From what tissue does it arise?
Answer
This is a craniopharyngioma. It arises from epithelial remnants of Rathke's pouch.
Card 308
This gross specimen displays what pathology?
Answer
Pale infarct
Card 309
This gross speciment shows what pathology?
Answer
Lacunar infarcts - cystic areas of infarction are characteristic
Card 310
What can be seen on this histology specimen taken from the brain?
Answer
These are red neurons, seen ~12 hours post-infarct
Card 311
Diagnosis?
Answer
Intracerebral hemorrhage - into the basal ganglia. Likely caused by rupture of a Charcot-Bouchard aneurysm.
Card 312
Diagnosis?
Answer
Multiple sclerosis. Note the grey plaques that are subtly apparent in the white matter of this path specimen.
Card 313
Histology specimen taken from the brain - what is this finding?
Answer
Neuritic plaque - composed of Aβ amyloid protein. Likely taken from a patient with Alzheimer's.
Card 314
Speciment taken from a brain. What can be seen?
Answer
Neurofibrillary tangle, composed of hyperphosphorylated tau protein. Patient likely had Alzheimer's.
Card 315
What can be seen in this histology speciment taken from the brain?
Answer
This is a Lewy body, composed of α-synuclein. Seen in Parkinson's or Lewy Body Dementia.
Card 316
Histology specimen taken from the brain. Diagnosis?
Answer
Spongiform encephalopathy - cannot distinguish specific type/etiology based on histology alone.
Card 317
Diagnosis?
Answer
Glioblastoma multiforme - classic 'butterfly lesion' that crosses the corpus callosum.
Card 318
Histology specimen taken from a brain mass. Diagnosis?
Answer
Glioblastoma multiforme - pseudopallisading tumor cells surrounding area of central necrosis
Card 319
Specimen taken from a brain mass. Diagnosis?
Answer
Meningioma - whorled pattern. Psammoma bodies not readily evident in this particular specimen.
Card 320
Specimen taken from a brain mass. Diagnosis?
Answer
Oligodendroglioma. "Fried egg" appearance of cells.
Pilocytic astrocytoma. Arrow points to a Rosenthal fiber.
Card 323
Speciment taken from a brain mass. Diagnosis?
Answer
Medulloblastoma. Small blue cells, Homer-Wright rosettes visible in the specimen
Card 324
Specimen taken from a brain mass. Diagnosis?
Answer
Ependymoma. Perivascular pseudorosettes can be seen.
Card 325
What mutation leads to achondroplasia? Specifically, what is the pathogenesis of the abnormal phenotype?
Answer
Achondroplasia represents an autosomal dominant, activating mutation in fibroblast growth factor receptor 3 (FGFR3).
Overexpression of FGFR3 inhibits osteoid deposition, which inhibits endochondral bone growth.
*Reminder: FGF stimulates angiogenesis and skeletal muscle development
Card 326
Why do patients with achondroplasia have short extremities but normal sized head and chest?
Answer
They have poor endochondral bone formation, which is the process by which long bones grow.
They have normal intramembranous bone formation, which is the process by which skull and chest form.
Card 327
A patient presents with multiple fractures, blue sclera and hearing loss. What does he have? What is the underlying defect (and inheritence pattern)?
Answer
Osteogenesis imperfecta: most commonly due to autosomal dominant defect in collagen type I synthesis
*Always good to keep in mind: defects in structural proteins are typically AD, while defects in enzymes tend to be AR.
Card 328
Why are the sclera blue in osteogenesis imperfecta patients?
Answer
Thinning of scleral collagen reveals underlying choroidal veins
Card 329
What is osteopetrosis? Describe the pathology that results from the most typical underlying genetic defect:
Answer
Osteopetrosis is an inherited defect in bone resorption (osteoclast function) resulting in abnormally thick bone that fractures easily.
Multiple genetic variants exist, but the most common mutation is a carbonic anhydrase II mutation, that prevents creation of the acidic environment necessary for bone resorption.
Card 330
What are the clinical features of osteopetrosis (5)? Can you describe the pathophysiology of each?
Answer
1) Bone fractures - thick bone is structurally disorganized and brittle
2) Anemia, thrombocytopenia, leukopenia, extramedullary hematopoiesis - bony myelophthisic process
3) Vision and hearing impairment - impingment of bone on cranial nerves
4) Hydrocephalus - due to narrowing of the foramen magnum
5) Renal tubular acidosis - dysfunctional carbonic anhydrase results in decreased tubular reabsorption of HCO3-
Card 331
What is the treatment for osteopetrosis, and why does it work?
Answer
Bone marrow transplant - it works because osteoclasts are specialized macrophages. New immune system will have functional carbonic anhydrase.
Card 332
What is vitamin D deficiency called in adults vs. children?
Answer
Adults: osteomalacia.
Children: rickets
Card 333
What are some clinical features of vitamin D deficiency (rickets) in children (4)?
Answer
1) Pigeon-breast deformity (inward bending of ribs, with anterior protrusion of the sternum)
2) Frontal bossing (enlarged forehead)
3) Rachitic rosary (knobs at the costochondral joints)
4) Bowing of the legs
*Clinical features 1-3 are due to the inappropriate deposition of osteoid in these locations
Card 334
What laboratory findings are seen in osteomalacia (4)?
Answer
1) Decreased serum calcium
2) Decreased serum phosphate
3) Increased PTH
4) Increased alkaline phosphatase (marker of osteoblast activation - in the absence of mineralization, osteoblasts just keep putting down osteoid; perhaps due to disruption of some feedback loop)
Card 335
What is osteoporosis?
Answer
Reduction in trabecular bone mass that results in porous bone and increased risk for fracture
Card 336
What are the lab findings in osteoporosis?
Answer
Totally, completely, 100% normal
Card 337
Why does Paget disease of bone occur?
Answer
It is due to imbalance of osteoclast and osteoblast function. The exact etiology is unknown, though thought to be viral (potentially related to measles exposure).
Card 338
What are the 3 distinct stages of Paget's disease of bone? What is the end result? What does the biopsy reveal?
Answer
1. Osteoclastic (bone resorbed)
2. Mixed osteoblastic and osteoclastic (osteoblasts react to osteoclastic activity)
3. Osteoblastic (osteoblast overreact)
The end result is thick, sclerotic bone that fractures easily.
Biopsy reveals a "mosaic pattern of lamellar bone".
Card 339
What are the clinical features of Paget's disease of bone and what causes each (5)?
Answer
1) Bone pain - microfractures
2) Increasing hat size - skull affected
3) Hearing loss - bone impingement on CN VIII
4) Lion-like facies - craniofacial bone involvement
5) Isolated elevated alkaline phosphatase
*Paget's is the single most common cause of isolated elevated alk phos in the over-40 patient population
Card 340
What are the treatments for Paget's disease of bone and how do they work (2)?
Answer
Calcitonin - inhibits osteoclast function
Bisphosphonates - induces osteoclast apoptosis
Card 341
What are the (2) complications of Paget's disease of bone?
Answer
1) High output cardiac failure (due to the formation of arteriovenous shunts in bone)
2) Osteosarcoma
Card 342
What are the causes and seeding patterns of osteomyelitis in children and adults?
Answer
Child: seeds in metaphysis, cause by transient bacteremia
Adult: seeds in epiphysis, caused by open wound bacteremia
Card 343
What common causes of osteomyelitis should be suspected in/in relation to:
a) overall
b) sexually active young adults
c) Sickle cell disease
d) Diabetics or IV drug users
e) Associated with cat/dog bites/scratches
f) Vertebral involvement
Answer
a) Overall: S. aureus
b) sexually active young adults: N. gonorrhoeae
c) Sickle cell disease: Salmonella
d) Diabetics or IV drug users: Pseudomonas
e) Associated with cat/dog bites/scratches: Pasteurella multocida
f) Vertebral involvement: tuberculosis ("Pott Disease")
Card 344
Where does an osteoma most commonly occur? What syndrome is it associated with?
Answer
It most commonly arises on the surface of facial bones. It is associated with Gardner syndrome.
*This is a benign tumor
Card 345
In whom does an osteoid osteoma typically present?
Answer
Young adults, < 25 years of age, more common in males.
Card 346
Compare and contrast osteoid osteoma with an osteoblastoma:
Answer
Osteoid osteoma is small (< 2 cm), arises in cortex of long bones, and responds to aspirin.
Osteoblastoma is larger (> 2 cm), arises in the vertebrae, and does not respond to aspirin.
Card 347
What type of bone tumor presents on imaging as a bony mass with a radiolucent core? Why does it appear this way?
Answer
Osteoid osteoma
Central osteolasts produce osteoid (cartilage) that is more radiolucent than the surrounding rim of reactive bone.
Card 348
What is the most common benign tumor of bone? What is its characteristic gross feature?
Answer
Osteochondroma; possesses an overlying cartilage cap
Card 349
What part of the bone gives rise to an osteochondroma?
Answer
It arises from a lateral projection of the growth plate (metaphysis); bone is continuous with the marrow space
Card 350
What part of the bone gives rise to an osteosarcoma (osteogenic sarcoma)? Which bones are most commonly afflicted?
Answer
Arises in the metaphysis of long bones, usually the distal femur or proximal tibia (region of the knee)
Card 351
What part of the bone gives rise to Giant cell tumor (osteoclastoma)?
Answer
Arises in the epiphysis of long bones, usually the distal femur or proximal tibia
*This is practically the only tumor type that arises in the epiphysis
Card 352
Which bone tumor has characteristic "soap bubble" appearance on imaging?
Answer
Giant cell tumor (osteoclastoma)
Card 353
How does osteosarcoma appear on imaging?
Answer
Has a classic "sunburst" appearance with a lifting of the periostium known as "Codman's triangle"
Card 354
Which bone tumor is associated w/ the (11:22) translocation?
Answer
Ewing sarcoma
Card 355
Which bone tumor has a characteristic "onion-skin" appearance on imaging?
Answer
Ewing sarcoma
Card 356
What type of cell does Ewing sarcoma arise from?
Answer
Ewing sarcoma represents a malignant proliferation of poorly-differentiated cells derived from neuroectoderm
Card 357
What is the most common benign bone tumor?
Answer
Osteochondroma
Card 358
Where does a chondroma typically arise? A chondrosarcoma?
Answer
1) Chondroma typically arises in the medulla of small bones of the hands and feet
2) Chondrosarcoma typically arises in the medulla of the pelvis or central skeleton
Card 359
Which type of metastatic tumor produces osteoblastic lesions (in contrast to all other bone mets, which produce osteoclastic leasions)?
Answer
Prostate carcinoma
Card 360
What type of collagen is found in cartilage?
Answer
Type II (hyaline cartilage)
Card 361
What is the most common benign soft tissue tumor in adults? What is the most common malignant soft tissue tumor in adults?
Answer
Lipoma; liposarcoma
Card 362
What is the characteristic cell of a liposarcoma?
Answer
the lipoblast
Card 363
What is the most common malignant soft tissue tumor in children?
Answer
Rhabdomyosarcoma
Card 364
Rhabdomyoblasts (characteristic cell of rhabsomyosarcoma) classically stains positive for which cellular marker?
Answer
Desmin ("rhabdo" = muscle)
Card 365
Where does rhabdomyosarcoma classically present in a young girl? Where is the overall most common presenting site?
Answer
The vagina (this is "sarcoma botryoides")
Head and neck is most common site otherwise.
Card 366
What pathologic process is evident in this X-ray?
Answer
Osteopetrosis, note how thick the bone has become
Card 367
What histological finding does this slide present us with?
Answer
"Mosaic pattern" of lamellar bone - characteristic of Paget's
Card 368
What pathology can be seen in this image?
Answer
Bony mass with radiolucent core - this is osteoid osteoma (benign tumor of osteoblasts)
Card 369
This is a gross specimen of what pathology?
Answer
Osteochondroma - lateral projection of bone plate, contiguous with marrow space
Card 370
What type of tumor does this histological specimen depict?
Answer
Osteosarcoma - note the large pleiomorphic cells producing osteoid
Card 371
What pathology does this histological specimen depict?
Answer
Giant cell tumor - take note of the multinucleated giant cells
Card 372
What pathology is depicted in the histological specimen below?
Answer
Ewing Sarcoma - small round poorly differentiated cells
Card 373
Though achondroplasia is considered to be an autosomal dominant inherited disease, how do most patients acquire the mutation?
Answer
Most mutations seen in achondroplasia are sporadic and assoicated with increased paternal age.
*Note that if two parents with achondroplasia both pass on a mutant allele, the homozygous child rarely lives past the first few months of life.
Card 374
Compare and contrast endochondral and intramembraneous bone formation:
Answer
Endochondral bone formation is characterized by formation of a cartilage matrix which is then replaced by bone. Long bones (appendicular skeleton) form this way.
Intramembraneous bone formation is characterized by bone formation without a pre-existing cartilage matrix. Flat bones (axial skeleton) form this way.
Card 375
How does vitamin D deficiency result in defective bone mineralization?
Answer
Osteoblasts normally produce osteoid, which is then mineralized with calcium and phosphate to form bone. Low vitamin D results in low levels of calcium and phosphate, so the osteoid is unable to be mineralized.
Card 376
Where do humans obtain their vitamin D?
Answer
85% is synthesized in the skin upon exposure to sunlight
15% is obtained in the diet
Card 377
How is the inactive form of vitamin D activated (2 steps, be specific)?
Answer
1) 25-hydroxylation by the liver
2) 1-a-hydroxylation by the proximal tubule cells in the kidney
Card 378
In what 3 places does vitamin D act to raise serum calcium and phosphate?
1) Decreased sun exposure
2) Poor diet
3) Malabsorption
4) Liver failure (no 25-hydroxylation)
5) Renal failure (no 1-a-hydroxylation)
Card 380
How is the the risk of osteoporosis estimated?
Answer
1) Based on peak bone mass (achieved by 30 years - 1% loss each year thereafter)
2) Lack of weight-bearing exercise, poor diet or decreased estrogen all contribute additional risk.
Card 381
What are the 2 forms of osteoporosis?
Answer
Senile and postmenopausal
Card 382
Clinical features of osteoporosis? Where specifically can fractures occur?
Answer
1) Bone pain
2) Kyphosis
3) Fractures in weight-bearing areas such as the vertebrae, hip, and distal radius
Card 383
How is bone density measured?
Answer
DEXA can
Card 384
What are 2 approved treatments for osteoporosis? One debated treatment? One contraindicated therapeutic?
Answer
1) Exercise, vitamin D, and calcium - limits bone loss
2) Bisphosphonates - induce osteoclast apoptosis
3) Estrogen replacement therapy is debated
4) Glucocorticoids contraindicated
Card 385
How are lytic foci described in cases of osteomyelitis (2 important "vocabulary words")?
Answer
Lytic focus is surrounded by sclerosis of bone.
The lytic focus is called the sequestrum, and the sclerosis is called the involucrum.
Card 386
How is the osteomyelitis diagnosis made?
Answer
Blood culture
Card 387
Avascular/aseptic necrosis (ischemic necrosis of the bone) can be caused by what 5 things?
Answer
1) Trauma
2) Fracture
3) Steroids
4) Sickle cell anemia
5) Caisson disease (decompression sickness, i.e. "the Bends")
Card 388
What are the 2 major complications of avascular (aseptic) necrosis of the bone?
Answer
Osteoarthritis and fracture
Card 389
What is a rare but highly undesirable complication of osteochondroma?
Answer
Progression of the overlying cartilage plate to chondrosarcoma
Card 390
What is an osteosarcoma (what is the malignant cell)?
Answer
A malignant proliferation of osteoblasts
Card 391
What are the risk factors for developing an osteosarcoma (4)?
Answer
1) Age - peak incidence in teens
2) Familial retinoblastoma
3) Paget disease
4) Radiation exposure
Card 392
How does osteosarcoma most typically present?
Answer
As a pathologic fracture (patients come in with broken bone following minor trauma or no recollection of trauma) or
bone pain with swelling
Card 393
In whom do giant cell tumors typically occur?
Answer
Young adults
Card 394
In whom does Ewing sarcoma typically arise? Where does it arise?
Answer
Male children < 15 years of age
Diaphysis of long bones
Card 395
Describe the anatomy of the articular surface of a synovial joint (3 aspects):
Answer
1) Articular surface of adjoining bones is made of hyaline cartilage
2) is surrounded by a joint capsule
3) Capsule lining (synovium) secretes fluid rich in hyaluronic acid.
Card 396
What is the most common type of arthritis?
Answer
Osteoarthritis
Card 397
What are 3 major risk factors for the development of osteoarthritis?
Answer
Age, obesity, trauma
*Note that "weight bearing exercise" is not really considered a risk factor
Card 398
What joints are affected by osteoarthritis?
Answer
Hips, lower lumbar spine, knees, DIPs, PIPs.
*Wrists and ankles tend to be spared
Card 399
What is the classic presentation of osteoarthritis?
Answer
Joint stiffeness in the morning that worsens over the course of the day.
Card 400
What are 3 pathologic features of osteoarthritis?
Answer
1) Disruption of the cartilage that lines the the articular surface; floating fragments are called "joint mice"
2) Eburnation (polishing) of the subchondral bone
3) Osteophyte formation (reactive bony outgrowths)
Card 401
In cases of osteoarthritis, in what joints do osteophytes typically arise?
Answer
In the DIPs and PIPs
Card 402
In whom does rheumatoid arthritis typically arise? What HLA type is it associate with?
Answer
Women of late child-bearing age; HLA-DR4
Card 403
What is the hallmark pathology of rheumatoid arthritis?
Answer
Proliferative synovitis leading to formation of inflamed granulation tissue; leads to destruction of cartilage and ankylosis (fusion of the joint)
Card 404
What are two key ways in which osteoarthritis and rheumatoid arthritis can be distinguished?
Answer
In RA, morning stiffness improves with activity; it worsens in OA.
In RA, the DIPs are usually spared (and the wrist may be involved)
Card 405
What joints are classically involved in rheumatoid arthritis?
What are rheumatoid nodules? What is the classic histological description?
Answer
Little nodules of necrosis surrounded by pallisading epithelioid histiocytes that arise in skin and visceral organs. Found in patients with rheumatoid arthritis.
Card 407
What is a Baker cyst?
Answer
Swelling of the bursa behind the knee. It is a potential symptom of rheumatoid arthritis.
Card 408
What is rheumatoid factor?
Answer
Nonspecific marker of rheumatoid arthritis: an IgM antibody against the Fc portion of IgG.
It can be used to monitor disease activity.
Card 409
What are the 3 seronegative spondyloarthropathies?
In whom does ankylosing spondylitis present? How does it present (3 symptoms)?
Answer
Young males.
Presents with lower back pain (fusion of the vertebrae) - uveitis and aortitis also both possible
Card 412
In whom does Reiter syndrome typically present? How does it present?
Answer
Young males, following GI or Chlamydia infection.
Presents with conjuncitivitis, urethritis, and arthritis. "Can't see, can't pee, can't climb a tree."
Card 413
In whom does psoriatic arthritis commonly present? How does it present?
Answer
Presents in 10% of patients with psoriasis.
Frequently involves DIPs of the hands and feet, leading to "sausage" fingers and toes.
Card 414
What are two major causes of infectious arthritis?
Answer
1) Gonorrhea - young adults, most common cause
2) S. aureus - older children and adults
Card 415
What type of crystals are deposited in gout?
Answer
Monosodium urate (MSU) crystals.
Card 416
What is the etiology of hyperuricemia in primary gout? How do gout attacks occur?
Answer
Trick question - we don't know how the hyperuricemia occurs.
The mechanism behind the inflammation is that neutrophils phagocytose urate crystals, release chemotaxic inflammatory mediators, then lyse and release the crystals in a postive feedback loop that amplifies the inflammatory response.
Card 417
Secondary gout is seen in what 3 conditions?
Answer
1) Leukemia/myeloproliferative disorders - this includes things like polycythemia vera, because increased cell turnover; also "tumor lysis syndrome"
2) Lesch-Nyhan - XLR defect in HGPRT
3) Renal insufficiency
Card 418
What is podagra?
Answer
Common presenting symptom of gout - exquisitely painful arthritic toe
Card 419
What are two potential triggers of gout?
Answer
Meat and alcohol
Card 420
What are two sequelae of long-term gout?
Answer
1) Development of tophi (white, chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in soft tissue and joints)
2) Renal failure - urate crytal deposition in kidney tubules
Card 421
What laboratory findings would you expect in gout?
Answer
Synovial fluid aspirate shows needle-shaped crystals with negative birefringance
Card 422
What is pseudogout?
Answer
Resembles gout clinically, but is due to deposition of calcium pyrophosphate dihydrate (CPPD) crystals, not MSU. Synovial fluid will show rhomboid crystals with weakly positive birefringance under polarized light.
Card 423
What makes birefringance "positive" or "negative" ?
Answer
"Negative" refers to crystals having a red/yellow coloration when their long axis is parallel to a polarized red filter, and blue when perpendicular. Positive is the opposite.
Card 424
What causes dermatomyositis?
Answer
Unclear - some cases associated with carcinoma, specifically ovarian carcinoma
Card 425
What are the 3 clinical features of dermatomyositis?
Answer
1) Bilateral proximal weakness (can't comb hair)
2) Rash of the upper eyelids (heliotrope rash); malar rash may also present
3) Red papules on elbows, knuckles, knees (Gottron papules)
Card 426
What are 3 lab findings in dermatomyosits? (Be detailed)
Answer
1) Increased creatinine kinase
2) Positive ANA and anti-Jo-1 antibody
3) Perimysial inflammation with perifasicular atrophy on biopsy (CD4+ mediated)
*Note that dermatomyositis can in some instances be a paraneoplastic syndrome associated with ovarian cancer
Card 427
What is the treatment for dermatomyositis?
Answer
Corticosteroids
Card 428
What are three key ways in which dermatomyositis and polymyositis are distinguished?
Answer
1) Polymyositis is an inflammatory process of the skeletal muscle only; dermatomyositis involves skin as well.
2) Polymyositis involves endomysial inflammation, whereas dermatomyositis is perimysial
3) Polymyositis is CD8+ mediated, dermatomyositis is CD4+
Memory Tips:
CD4⁺ T cells in dermatomyositis ellicit an autoimmune response all over—'around' the fibers, and in the skin as well.
CD8⁺ T cells in polymyositis ellicit a local autoimmune response in the muscle, 'within' the fibers.
Card 429
X-linked muscular dystrophy can arise spontaneously - why?
Answer
The X-linked muscular dystrophies involve deletions and mutations of the dystrophin gene (dystrophin anchors muscle cytoskeleton to the ECM). This is the single largest gene in the human body, and is, as such, prone to mutation.
Card 430
How does Duchenne muscular dystrophy clinically present (3 features)?
Answer
1) Proximal weakness beginning at 1 year of age (pelvic girdle usually involved first - Gower maneuver)
2) Calf pseudohypertrophy (replacement of muscle with fibrofatty tissue)
3) Elevated serum creatinine kinase
Card 431
How do Duchenne patients die?
Answer
Cardiac or respiratory failure (heart or diaphragm gives out)
Card 432
Against what target are antibodies in myasthenia gravis directed?
Answer
The postsynaptic acetylcholine receptor at the NMJ
Card 433
How does MG present clinically?
Answer
Muscle weakness that worsens with use; affects eyes (ptosis and diplopia);
improves with administration of anticholinesterases
Card 434
What underlying pathologies can MG be associated with?
Answer
Thymic hyperplasia or thymoma
*Note that thymectomy can improve symptoms
Card 435
Against what target are antibodies in Lambert-Eaton syndrome targeted?
Answer
Presynaptic voltage-gated calcium channels of the NMJ
Card 436
What pathology is Lambert-Eaton usually associated with?
Answer
It is a paraneoplastic syndrome usually seen in small cell carcinoma of the lung
Card 437
What are the clinical features of Lambert-Eaton?
Answer
Proximal weakness that improves with use; eyes are usually spared; anticholinesterases do not improve symptoms
*Important to note: the reason anticholinesterases do not improve symptoms is because they act on the wrong target. In LE, the presynaptic calcium channels, which must allow influx of calcium in order for secretory ACh vesicles to fuse with membrane and release contents, are blocked.
Card 438
What are the 5 layers of the epidermis? What features are unique to each?
Answer
1) Corneum (keratin and anucleate cells)
2) Lucidem (thin layer of clear cells)
3) Granulosum (granules in keratinocytes)
4) Spinosum (desmosomes)
5) Stratum basalis (stem cells)
Card 439
What is the pathogen that is associated with acne vulgaris? How does it cause acne?
Answer
Propionibacterium acnes infection produces lipases that break down sebum, releasing proinflammatory fatty acids
Card 440
How does psoriasis present?
Answer
Well-circumscribed, salmon-colored plaque with silvery scale, usually on extensor surfaces and the scalp.
Card 441
Why does psoriasis occur; what cell in the epidermis is involved?
Answer
Possible autoimmune etiology; associated with HLA-C. Excessive keratinocyte proliferation.
Card 442
What are the 4 histological features of psoriasis?
Answer
Auspitz sign:
bleeding when the scale is picked off - exposure of dermal papillae.
Parakeratosis:
Hyperkeratosis with retention of keratinocyte nuclei in the corneum
Munro microabscesses:
collections of neutrophils in the stratum corneum
Acanthosis:
hypertrophy of the stratum spinosum
Card 443
What is a pruritic, planar, polygonal, purple plaque suggestive of?
Answer
Lichen planus
Card 444
Lichen planus shows what on histologic examination?
Answer
Inflammation of the dermal-epidermal junction with "saw-tooth" appearance.
Card 445
What virus is associated with lichen planus?
Answer
Hepatitis C (chronic infection)
Card 446
What disease is associated with autoimmune destruction of desmosomes between keratinocytes?
Answer
Pemphigus vulgaris
Card 447
What is the specific autoantibody in pemphigus vulgaris?
Answer
IgG antibody against desmoglein (type II hypersensitivity)
Card 448
What derm pathology shows a "tombstone" appearance on histology?
Answer
Pemphigus vulgaris - basal layer cells remain attached to to the basement membrane via hemidesmosomes.
Card 449
What derm pathology shows a "fish net" patterns on immunofluoresence?
Answer
Pemphigus vulgaris
Card 450
Which derm pathology (pemphigus vulgaris or bullous pemphigoid) is more likely to involve the oral mucosa?
Answer
Pemphigus vulgaris
Card 451
Which derm pathology is due to IgG antibody against dystonin?
Answer
Bullous pemphigoid
*Note: dystonin (DST) = Bullous pemphigoid antigen 1 (BPAG1), a component of hemidesmosomes (HD).
Antibodies against BP180 (also an HD component) are also possible.
Card 452
Between pemphigus vulgaris and bullous pemphigoid, which presents with tense and which with flaccid bullae?
What derm path that is a cup-shaped tumor filled with keratin debris that arises rapidly and regresses spontaneously?
Answer
Keratoacanthoma
Card 462
Keratinocytes contain melanin pigmentation. How is it produced?
Answer
Melanocytes in the basal layer produce melanosomes, and pass them on to the keratinocytes above them.
Card 463
Which embryonic cell type are melanocytes derived from?
Answer
Neural crest cells
Card 464
Name the disease caused by autoimmune destruction of melanocytes.
Answer
Vitiligo
Card 465
Which disorder is a congenital defect of an enzyme needed for melanin production? What enzyme is this usually? What cancers are these patients at increased risk for?
Answer
Albinism;
Tyrosinase;
SCC, BCC and melanoma
Card 466
Why does a freckle (ephelis) look tan-dark brown and darker when exposed to sunlight?
Answer
It has an increased number of melanosomes (melanocytes are NOT increased).
Card 467
What toxins of Staph aureus cause Staphylococcal Scalded Skin Syndrome?
Answer
Exfoliative A and B toxins - results in epidermolysis (sloughing of the stratum granulosum)
Card 468
What causes molluscum contagiosum? What is the name of the cytopasmic inclusion?
Answer
Poxvirus
Cytoplasmic inclusion = molluscum bodies
Card 469
Diagnosis?
Answer
Molluscum contagiosum
Card 470
What is depicted in this histological specimen?
Answer
Bullous pemphigoid: note how there is complete separation of layers between the basal cells and underlying basement membrane (no "tombstone" histology)
Card 471
Skin Biopsy. What condition is this?
Answer
Basal Cell Carcinoma
Palisading of cells at the periphery
Card 472
What is depicted in the histology specimen pictured below?
What are the (2) treatments for acne and how do they work?
Answer
Benzoyl peroxide (antimicrobial)
Vitamin A derivatives (reduce keratin production)
Card 477
What is erythema multiforme?
Answer
A hypersensitivy reaction (type IV) characterized by targetoid rash and bullae.
Card 478
What are the 4 causes of erythema multiforme?
Answer
1) Infection (HSV or mycoplasma)
2) Drugs (penicillin and sulfonamides)
3) Autoimmune disease
4) Malignancy
Card 479
Erythema multiforme with mucosal involvement and fever is termed what?
Answer
Stevens-Johnson Syndrome
Card 480
What is toxic epidermal necrolysis and what is it most commonly caused by?
Answer
Severe form of Stevens Johnson syndrome (SJS) with diffuse sloughing of the skin:
most often due to an adverse drug reaction.
Card 481
What is the most common cutaneous malignancy? How is it treated?
Answer
Basal cell carcinoma. Surgical excision - nothing else is needed, it rarely metastasizes.
Card 482
What are the 3 common risk factors for both basal cell and squamous cell carcinoma?
Answer
1) Exposure to sunlight
2) Albinism
3) Xeroderma pigmentosum
Card 483
What is the significance of actinic keratosis?
Answer
Precursor lesion to squamous cell carcinoma. Presents as a scaly plaque on the face, back, or neck.
Card 484
Melanin is synthesized from what amino acid precursor?
Answer
Tyrosine
Card 485
A "mask like" hyperpigmentation of the cheeks is known as what? What is it associated with?
Answer
Melasma. Associated with pregnancy and oral contraceptive use.
Card 486
What is a nevus?
Answer
A benign neoplasm of melanocytes
Card 487
What is the difference between a congenital and acquired nevus?
Answer
Congenital nevi are present at birth and usually grow hair.
Acquired nevi occur later in life and do not produce hair.
Card 488
How does a junctional acquired nevus become an intradermal nevus?
Answer
1) Nest of melanocytes exists in the dermal/epidermal junction (this is a junctional nevus)
2) Grows by extension into the dermis (compound nevus)
3) Junctional component is lost, resulting in an intradermal nevus.
Card 489
What is a melanoma?
Answer
A malignant neoplasm of melanocytes
Card 490
What is dysplastic nevus syndrome?
Answer
An autosomal dominant inherited condition that predisposes an individual to developing many dysplastic nevi. These may progress to melanoma.
Associated with mutations on chromosome 9p21 (CDK2NA), which causes loss of p16 (tumor suppressor).
Card 491
Describe the "ABCDE" growth of melanoma:
Answer
1) Asymmetrical
2) Borders are irregular
3) Color not uniform
4) Diameter > 6 mm
5) Evolution
Card 492
Describe the two growth phases of melanoma:
Answer
1) Radial growth - horizontal growth along the epidermis and superficial dermis
2) Vertical growth into the deep dermis
Card 493
What is the most important factor in prognosticating the metastatic potential of melanoma?
Answer
The Breslow thickness, i.e. the distance from the superficial epidermal granular cell layer to the deepest intradermal tumor cells
Card 494
What are the 4 variants of melanoma? What is a unique feature of each?
Answer
1) Superficial spreading - early radial growth (great prognosis)
2) Lentigo maligna - radial growth (also good prognosis)
3) Nodular - early vertical growth (poor prognosis)
4) Acral lentiginous - arises on palms and toes, not associated with UV exposure
Card 495
What are risk factors for cellulits?
Answer
Recent surgery,
trauma, or
insect bite.
Card 496
Distinguish the sloughing seen in scalded skin syndrome and Stevens Johnson syndrome/toxic epidermal necrolysis:
Answer
In scalded skin syndrome, seperation of dermal layers occurs at the level of the stratum granulosum.
SJS/TEN represents a separation at the dermal/epidermal junction.
Card 497
What is verruca? What is the characteristic feature?