Clin/Path Flashcards
1
Q
Congenital hypothyroidism (cretinism) clinical presentation
A
Usually asymptomatic at birth (rarely causes delayed meconium passage)
After maternal thyroxine wanes (weeks to months):
Lethargy, poor feeding
Enlarged/protruding anterior fontanelle
Protruding tongue, puffy face, umbilical hernia (all of these are due to accumulation of matrix substances cutaneously and internally)
Constipation
Prolonged jaundice
Dry skin
2
Q
Congenital hypothyroidism (cretinism) diagnosis
A
↑ TSH & ↓ free thyroxine levels
Newborn screening
3
Q
Congenital hypothyroidism (cretinism) treatment
what to avoid with it
A
Levothyroxine by 2 weeks old can normalize cognitive and physical development
Avoid co-administration with soy products, iron, or calcium.
4
Q
Congenital hypothyroidism (cretinism) prognosis if treated
A
No deficits if treatment started in neonatal period
So make sure to screen for this
5
Q
Congenital hypothyroidism (cretinism) prognosis if untreated
A
neurocognitive dysfunction (eg, ↓ intelligence quotient)
6
Q
Congenital hypothyroidism (cretinism) etiology
A
thyroid dysgenesis (agenesis, hypoplasia, or ectopy), and iodine deficiency is a common cause in areas endemic for iodine deficiency (eg, Europe).
TSH resistance due to a mutation in the TSH receptor gene
7
Q
T4 functions
A
essential for normal brain development and myelination during early life
stimulation of protein synthesis as well as carbohydrate and lipid catabolism in many cells
8
Q
Down syndrome
clinical
A
Hypotonia hypothyroidism upslanting palpebral fissures bilateral epicanthal folds single palmar crease
9
Q
Galactosemia etiology
A
galactose-1-phosphate uridyltransferase deficiency
10
Q
Galactosemia clinical
A
jaundice, vomiting, hepatomegaly, and lethargy after ingesting galactose in breast milk or formula in the first few days of life
11
Q
Hirschsprung disease etiology
A
abnormal migration of neural crest cells into the rectosigmoid colon
12
Q
Hirschsprung disease clinical
A
failed meconium passage and bilious emesis in a newborn due to lack of ganglion cells in rectosigmoid colon impeding gastrointestinal motility
13
Q
Phenylketonuria (PKU) etiology
A
phenylalanine hydroxylase deficiency resulting in hyperphenylalaninemia
14
Q
Phenylketonuria (PKU) clinical
A
developmental delay, light pigmentation, and a musty body odor
15
Q
DiGeorge syndrome (DGS) etiology
A
neural crest fails to migrate into the derivatives of the third (affects inferior parathyroid and thymus) and fourth (affects superior parathyroid) pharyngeal/branchial pouches
16
Q
DiGeorge syndrome (DGS) labs
A
hypocalcemia (due to parathyroid hypoplasia)
T cell deficiency (due to thymic hypoplasia)
17
Q
Hypocalcemia presents as:
A
increased neuromuscular excitability, which manifests as tetany, carpopedal spasms, or seizures.
Chvostek sign -
Tapping on the facial nerve usually elicits twitching of the nose and lips
Trousseau sign -
inflation of the blood pressure cuff leads to carpopedal spasm
18
Q
DiGeorge syndrome (DGS) imaging:
A
absence of thymic shadow (may be written as chest x-ray reveals decreased soft-tissue attenuation in the right anterior mediastinum) which reflects thymic hypoplasia
19
Q
What complication may thymic aplasia lead to and why?
A
absence reflects thymic hypoplasia, which leads to T cell dysfunction and results in recurrent viral, fungal, and protozoan infections.
20
Q
What microdeletion is associated with DiGeorge Syndrome?
A
22q11.2 microdeletion
21
Q
What is seen clinically in a DiGeorge syndrome patient when the first and second pharyngeal/branchial pouches are involved as well?
A
hypertelorism, short palpebral fissures, micrognathia, bifid uvula, and cleft palate
22
Q
Anencephaly etiology
A
neural tube defect due to failure of the anterior neuropore to close
23
Q
foramen cecum
A
depression on the tongue that represents the embryological remnant of the superior end of the obliterated thyroglossal duct
24
Q
thyroglossal cyst etiology
A
due to a persistent thyroglossal duct
25
thyroglossal cyst location
midline neck mass
26
Rathke pouch
invaginated oral ectoderm that eventually develops into the anterior pituitary
27
Craniopharyngiomas etiology
arise from remnants of the Rathke pouch
28
Craniopharyngiomas clinical
hypopituitarism, hydrocephalus, and diabetes insipidus
29
Persistence of second branchial cleft (ie, second pharyngeal groove)
This is normally obliterated in utero but persistence leads to a branchial cleft cyst between the angle of the mandible and sternocleidomastoid muscle.
30
Incretins
gastrointestinal hormones produced by the gut mucosa that stimulate pancreatic insulin secretion in response to sugar-containing meals. This response is independent of blood glucose levels, and typically occurs prior to any elevation in blood glucose level following a meal
31
Two hormones with incretin effects are
glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (glucose-dependent insulinotropic peptide, GIP).
32
Insulin-like growth factor-1 produced because?
produced by the liver in response to stimulation by growth hormone.
33
Insulin-like growth factor-1 function
It functions as a mitogen and as an inhibitor of apoptosis
34
Somatostatin is produced by
cells in the stomach, small bowel and pancreas ("delta cells")
35
Somatostatin function
decreases the secretion of secretin, cholecystokinin, glucagon, insulin, gastrin and growth hormone
36
Secretin produced because?
hormone produced in the duodenum in response to increased luminal acidity.
37
Secretin function
stimulates the release of bicarbonate-rich secretions from the pancreas, gallbladder and duodenum. It also increases the activity of cholecystokinin.
38
Cholecystokinin is produced by
duodenum in response to a fat or protein-rich meal.
39
Cholecystokinin functions
inhibition of further gastric emptying, stimulation of pancreatic enzyme secretion and stimulation of bile production and gallbladder contraction
40
Type 1 diabetes mellitus demographic
genetically susceptible individuals who are exposed to triggering environmental factors (eg, viral infections, environmental toxins, dietary components).
41
Type 1 diabetes mellitus etiology
autoimmune (cell-mediated) response against pancreatic beta cells that leads to progressive loss of beta cell mass (this causes low levels of low circulating islet amyloid polypeptide)
42
Type 1 diabetes mellitus clinical
develop once >90% of beta cells are destroyed
excessive thirst and polyuria
43
insulitis
Infiltration of islets by inflammatory cells in T1DM and is more prominent during the early stages of disease.
44
type 2 diabetes mellitus development risk factors
Abdominal visceral fat deposition and excessive body weight because they cause insulin resistance
45
Maturity-onset diabetes of the young genetics
autosomal dominant disease
46
Maturity-onset diabetes of the young etiology
mutations that impair glucose sensing and insulin secretion by pancreatic beta cells
47
Maturity-onset diabetes of the young clinical
non-insulin-dependent diabetes at a young age (<25) and accounts for <5% of all cases of diabetes mellitus
48
Islet amyloid polypeptide secreted from?
secreted along with insulin from pancreatic beta cells.
49
T2DM etiology
Insulin resistance accompanied by relative insulin deficiency is the main cause
50
T2DM histology
Amyloid deposition occurs in the islets
51
exogenous thyrotoxicosis etiology
abuse of thyroid preparations (eg, levothyroxine, porcine thyroid extracts) or inadvertently due to errors in treatment of hypothyroidism
52
exogenous thyrotoxicosis clinical
resemble endogenous hyperthyroidism and include weight loss, tremor, heat intolerance, and tachycardia/palpitations
53
exogenous thyrotoxicosis labs
suppressed TSH
suppressed RAIU
suppressed serum thyroglobulin (because thyroid metabolic activity is low)
elevated Triiodothyronine (T3) (because exogenous levothyroxine is readily converted to T3)
elevated free thyroxine (T4)
54
Radioactive iodine uptake (RAIU)
radioiodine tracer that is administered followed by scintigraphy of the thyroid gland
RAIU correlates with the organification of iodine and the synthesis of new thyroid hormone
55
Thyroglobulin
large glycoprotein in thyroid follicles that serves as a source of tyrosine residues for thyroid hormone synthesis
56
Graves disease labs
↓Serum TSH
↑Serum thyroglobulin
↑ Radioiodine uptake (due to excessive TSH receptor stimulation)
57
Graves disease etiology
due to autoantibodies that activate the TSH receptor and induce thyroid hormone production
58
subacute granulomatous thyroiditis
destruction of thyroid follicles and the release of preformed thyroid hormone
59
subacute granulomatous thyroiditis labs
Elevated thyroglobulin
elevated T3
decreased TSH
increased serum thyroglobulin
60
TBG levels in hyperestrogenic states
elevated
61
subacute granulomatous thyroiditis clinical
Painful** thyroid enlargement
| Transient hyperthyroid symptoms (due to release of stored thyroid hormone)
62
subacute granulomatous thyroiditis etiology
typically follows an acute viral illness and is thought to be due to a cross-reacting immune response against viral proteins or tissue antigens released during cellular injury
63
subacute granulomatous thyroiditis diagnosis
↑ ESR & CRP (serum acute phase markers)
| ↓ Radioiodine uptake (low TSH levels suppress synthesis of new thyroid hormone)
64
subacute granulomatous thyroiditis treatment
self-limited and resolves in <6 weeks, although patients may have a brief hypothyroid phase before returning to a euthyroid state
65
subacute granulomatous thyroiditis histology
initially characterized by a neutrophilic infiltrate with microabscess formation, which, as the disease progresses, is replaced by a more generalized inflammatory infiltrate with macrophages and multinucleated giant cells
66
Hashimoto thyroiditis etiology
Autoimmune etiology
67
Hashimoto thyroiditis clinical
Diffuse, painless thyroid enlargement
Predominant hypothyroid features (eg, fatigue, cold intolerance)
**most common cause of hypothyroidism
68
Hashimoto thyroiditis diagnosis
Positive TPO antibody**
| Variable radioiodine uptake
69
Hashimoto thyroiditis histology
Lymphocytic infiltrate with well-developed germinal centers
| Hürthle cells (eosinophilic epithelial cells)
70
Papillary thyroid cancer histology
branching papillary structures with concentric calcifications (psammoma bodies)
71
Papillary thyroid cancer gross
nodular enlargement
72
Riedel thyroiditis histology
extensive fibrosis of the thyroid gland that extends into surrounding tissues
73
Riedel thyroiditis gross
thyroid gland is rock-hard and nontender
74
Graves disease histology
Diffusely hyperplastic follicles with tall, crowded cells forming intrafollicular projections
75
Hashimoto thyroiditis aka
Chronic lymphocytic thyroiditis
76
secondary (central) hyperthyroidism labs
elevated TSH, elevated T3, T4
77
secondary (central) hyperthyroidism etiology
most commonly due to TSH-secreting pituitary adenoma
78
Hyperthyroidism clinical
fatigue, weight loss, and palpitations associated with elevated thyroid hormone levels. Hyperadrenergic signs (eg, lid lag, tremor) are also common
79
Hyperthyroidism labs
Low TSH, elevated T3 and T4
80
secondary (central) hyperthyroidism clinical
diffuse goiter (because excess TSH causes generalized hypertrophy of the thyroid gland)
81
Effect of estrogen on TBG and consequently the thyroid levels
Estrogen (eg, pregnancy, oral contraceptives) causes increased production of TBG, which lowers free thyroid hormone levels. A brief rise in TSH subsequently increases production of thyroid hormone to saturate the increased TBG binding sites, and the patient returns to a euthyroid state. Total T3 and T4 are elevated, but TSH and free hormone levels are normal
82
Painless thyroiditis histology
autoimmune destruction of thyroid follicles with release of preformed thyroid hormone
83
Thyroid cancer gross
hard, asymmetric goiter
84
Thyroid cancer clinical
Thyroid tissue adjacent to cancer may be compressed and nonfunctional, but the contralateral lobe can usually compensate and patients are typically euthyroid
85
Fecal occult blood testing
screens for colorectal cancer and improves mortality through earlier detection
86
Prostate-specific antigen
increased in some patients with prostate cancer but testing has not been shown to improve mortality from prostate cancer
87
Aspirin use significantly reduces the risk of
death from coronary heart disease in diabetic patients but is less effective than smoking cessation
88
most effective preventive intervention in almost all patients
Smoking cessation
89
Prolactinoma clinical in premenopausal vs postmenopausal woman
Premenopausal women: oligomenorrhea, amenorrhea (due to the inhibitory effect of prolactin on hypothalamic GnRH release), infertility, galactorrhea, hot flashes, decreased bone density
Postmenopausal women: mass-effect symptoms (headache, visual field defects)
90
Prolactinoma clinical in men
infertility, decreased libido, impotence, gynecomastia
91
Prolactinoma diagnosis steps
Serum prolactin (often >200 ng/mL)
Tests to rule out renal insufficiency (creatinine) & hypothyroidism (TSH, thyroxine)
MRI of the head/pituitary
92
Prolactinoma treatment
```
Dopamine agonist (cabergoline) (because of tonic inhibitory effect of dopamine on prolactin secretion)
Transsphenoidal surgery
```
93
Galactorrhea
abnormal secretion of breast milk not associated with pregnancy or breastfeeding
94
Galactorrhea etiology
most commonly due to excess prolactin, which directly stimulates milk secretion in the breasts
95
Prolactin regulation
prolactin is primarily under negative regulation by hypothalamic dopaminergic neurons via the pituitary stalk
96
Estrogen effect on galactorrhea
Estrogen stimulates prolactin gene transcription and secretion. Strongly estrogenic medications (eg, birth control pills) can potentially worsen rather than alleviate galactorrhea
97
Dopamine antagonists effect on galactorrhea
(eg, antipsychotics) directly increase prolactin secretion and can worsen galactorrhea
98
estrogen effect on prolactin
Estrogen stimulates prolactin gene transcription and secretion
99
TRH effect on prolactin
Thyrotropin-releasing hormone (TRH) stimulates secretion of prolactin by lactotrophs, although its role in regulating prolactin release is secondary to the inhibition of prolactin secretion by dopamine
100
Pulsatile Gonadotropin-releasing hormone (GnRH)
polypeptide that is normally released from the anterior hypothalamus in a pulsatile manner. GnRH is carried to the anterior pituitary via the portal circulation, where it stimulates FSH and LH production
101
FSH and LH function in ovaries
development of the dominant follicle in the ovaries. Optimal frequency and amplitude of GnRH pulses are crucial for FSH and LH release and subsequent ovulation
102
Anovulation due to hypogonadotropic hypogonadism clinical
common form of infertility
103
Anovulation due to hypogonadotropic hypogonadism treatment
pulsatile administration of GnRH and the ovulation occurs in most patients in 10-20 days
104
Signs of ovulation diagnosis
loss of a dominant follicle on ultrasound
surge in urine LH levels
rise in serum progesterone levels
rise in basal body temperature
105
Constant GnRH activity causes
down-regulation of the GnRH receptors on pituitary gonadotrophin cells, which suppresses LH and FSH secretion
106
When is long acting GnRH analog therapy used
when suppression of gonadal function is desired, such as in certain patients with prostate cancer, endometriosis, precocious puberty, or premenopausal breast cancer.
107
Hypercalcemia-induced constipation etiology
Primary hyperparathyroidism
Hypercalcemia of malignancy
Vitamin D toxicity
Milk-alkali syndrome
108
Hypercalcemia-induced constipation clinical
Decreased frequency/increased hardness of stools
Nausea, abdominal pain
Non-gastrointestinal symptoms: fatigue, polyuria, neuropsychiatric disturbance
109
Hypercalcemia-induced constipation pathophysiology
Inhibition of smooth muscle depolarization --> decreased intestinal contractility/motility
110
Primary hyperparathyroidism (PHPT) etiology
benign parathyroid adenoma that autonomously secretes parathyroid hormone (PTH), leading to increased bone resorption, increased renal calcium reabsorption, and increased intestinal calcium absorption (due to increased production of 1,25-dihydroxyvitamin D)
111
Hypercalcemia causes (pathology)
inhibits nerve depolarization by interfering with sodium movement through voltage-gated sodium channels, leading to impaired smooth muscle contraction and reduced colonic motility
112
Hypercalcemia clinical
constipation, crampy abdominal pain, and nausea. Other - acute pancreatitis (due to increased conversion of trypsinogen to trypsin) and peptic ulcer (due to increased release of gastrin).
113
Dyssynergic defecation pathology
altered passage of stool through the anorectum due to uncoordinated contraction and relaxation of pelvic floor muscles
114
Dyssynergic defecation etiology
obstetric complications during vaginal delivery
115
Dyssynergic defecation clinical
most patients have either anal sphincter dysfunction or the absence of perianal descent (this patient's rectal tone is normal)
116
Intestinal motor function is generally stimulated/inhibited by SNS/PNS
stimulated by the parasympathetic nervous system and inhibited by the sympathetic nervous system
117
Colon cancer clinical
intestinal obstruction, which can interfere with the passage of stool
118
Colon cancer labs
PTH suppression
| associated with hypercalcemia (bone metastasis)
119
Somatostatinoma clinical
hyperglycemia or hypoglycemia
steatorrhea (excessive fat in the feces)
gallbladder stones (because of poor gallbladder contractility, which is secondary to inhibition of cholecystokinin release)
120
Steatorrhea etiology
decreased secretion of secretin as well as a decrease in gastrointestinal motility
121
Hypochlorhydria etiology
decrease in gastrin release
122
Why cant somatostatin be used in clinical practice
because of its extremely short half-life
123
What to use instead of somatostatin in clinical practice
Somatostatin analogs (octreotide and lanreotide) have a longer plasma half-life
124
Syndrome of inappropriate antidiuretic hormone (SIADH) pathophysiology
Uncontrolled secretion of ADH
| Leads to water retention & impaired urinary water excretion
125
Syndrome of inappropriate antidiuretic hormone (SIADH) etiology
CNS disturbances (stroke, hemorrhage, trauma)
Medications (eg, carbamazepine, SSRIs, NSAIDs)
Lung disease (eg, pneumonia)
Malignancy (eg, small-cell lung cancer)
126
Syndrome of inappropriate antidiuretic hormone (SIADH) clinical
Nausea, forgetfulness (mild hyponatremia)
Seizures, coma (severe hyponatremia)
Euvolemia (eg, moist mucous membranes, no edema, no JVD)
**most common cause of hyponatremia following subarachnoid hemorrhage (SAH)
127
Syndrome of inappropriate antidiuretic hormone (SIADH) labs
Hyponatremia
Low serum osmolality
High urine osmolality
High urine sodium
128
11β-hydroxylase deficiency clinical
In genetically female infants, androgen excess leads to ambiguous genitalia, clitoral enlargement and partial fusion of the labioscrotal folds (virilization)
hypertension and hypokalemia
129
11β-hydroxylase function
converting 11-deoxycorticosterone to corticosterone and 11-deoxycortisol to cortisol
130
5α-reductase deficiency clinical
ambiguous genitalia in boys
Girls have normal genitalia
blood pressure and electrolytes are unaffected
131
5α-reductase deficiency causes
defective conversion of testosterone to dihydrotestosterone
132
17α-hydroxylase deficiency clinical
impaired sex steroid and cortisol synthesis, and increased production of mineralocorticoids
Girls are born with normal genitalia, but boys are born undervirilized (ambiguous genitalia)
hypertension and hypokalemia (mineralocorticoid excess)
do not undergo puberty (no sex steroids)
133
21-hydroxylase deficiency clinical
Girls are born with ambiguous genitalia (androgen excess) and frequently develop hypotension and hyperkalemia (mineralocorticoid deficiency)
134
21-hydroxylase deficiency labs
decreases glucocorticoid and mineralocorticoid synthesis and increases adrenal androgen production
135
Side-chain cleavage enzyme deficiency
Because this is the first enzyme in the steroidogenic pathway, deficiency impairs synthesis of all steroid hormones. Complete deficiency is lethal due to absent placental progesterone synthesis
136
Side-chain cleavage enzyme function
converts cholesterol to pregnenolone
137
Central hypothyroidism etiology
due to hypothalamic-pituitary dysfunction
```
Mass lesions (eg, pituitary adenoma)
Pituitary surgery, trauma, irradiation
Infiltrative disorders (eg, sarcoidosis, hemochromatosis)
Pituitary infarction (eg, Sheehan syndrome)
```
138
Central hypothyroidism clinical
Hypothyroid symptoms:
fatigue
hair loss
brittle nails
Mass-effect symptoms (eg, headache, visual field defects) if due to mass
139
Central hypothyroidism labs
Low free thyroxine (T4)
Low or inappropriately normal TSH
Other pituitary hormone deficiencies (eg, ACTH, prolactin, gonadotropins)
140
Central hypothyroidism vs primary hypothyroidism
Central hypothyroidism is much less common than primary hypothyroidism. However, when it occurs, other hypothalamic-pituitary systems may be affected and patients may develop deficiencies of other pituitary hormones (eg, low gonadotropin levels leading to amenorrhea).
141
Sheehan syndrome definition and etiology
ischemic necrosis of the pituitary gland and is typically caused by systemic hypotension during delivery.
142
Sheehan syndrome pathophysiology
During pregnancy, the pituitary gland enlarges due to estrogen-induced hyperplasia of lactotrophs, but the blood supply does not increase proportionally. Subsequent peripartum hemorrhage with hypotension can cause underperfusion of the pituitary gland with subsequent ischemic injury.
143
Primary hypothyroidism etiologies
```
Chronic autoimmune (Hashimoto) thyroiditis (MOST COMMON)
Postpartum thyroiditis
```
144
Postpartum thyroiditis
variant of Hashimoto thyroiditis that occurs within a year of pregnancy
145
Graves disease clinical
goiter and ocular manifestations (eg, proptosis, lid lag)
146
screening for Cushing syndrome
24-hour urinary cortisol assay
dexamethasone suppression test (for endogenous)
147
Initial tests for diabetes mellitus
fasting glucose, hemoglobin A1c, and oral glucose tolerance tests
148
initial evaluation of hereditary hemochromatosis
serum iron studies (eg, serum iron, ferritin, transferrin saturation)
149
hereditary hemochromatosis clinical
pituitary dysfunction with secondary (central) hypothyroidism, arthritis, diabetes mellitus, abnormal skin pigmentation, and hepatomegaly
150
blood supply to the thyroid and parathyroid glands
superior thyroid artery (a branch of the external carotid artery) and the inferior thyroid artery (a branch of the thyrocervical trunk)
151
cricothyroid muscle innervation
external branch of the superior laryngeal nerve course together in a neurovascular triad that originates superior to the thyroid gland and lateral to the thyroid cartilage
152
nerve most at risk of injury during thyroidectomy
The external branch of the superior laryngeal nerve is at risk of injury during thyroidectomy as it courses just deep to the superior thyroid artery
153
cricothyroid muscle O/I
originates on the cricoid cartilage and inserts on the lower border of the thyroid cartilage
154
cricothyroid muscle function/what will happen in an injury
tense the vocal cords, and denervation injury may cause a low, hoarse voice with limited range of pitch
155
DKA treatment
intravenous infusion of regular insulin, which allows for rapid adjustments in dose based on blood glucose levels. When given subcutaneously, regular insulin starts working within 30 minutes, peaks in 2-4 hours, and lasts 5-8 hours
156
Cushing syndrome clinical
weight gain, proximal muscle weakness, hypertension, and hyperglycemia
moon facies, enlarged fat pads, hypertension, and proximal muscle weakness
157
normal individuals - low-dose dexamethasone suppression testing results
suppress ACTH and cortisol levels through negative feedback
158
Cushing syndrome - low-dose dexamethasone suppression testing results
ACTH and cortisol levels are not suppressed
159
most common gluccocorticoid to cause cushing syndrome
most common with systemic agents (eg, prednisone), but can occasionally be seen with topical or inhaled glucocorticoids
160
LH function in males
LH stimulates the release of testosterone from the Leydig cells in the interstitium of the testicles
161
FSH function in males
FSH stimulates the release of inhibin B from the Sertoli cells in the seminiferous tubules of the testicles
stimulates the Sertoli cells to produce androgen-binding protein locally, within the seminiferous tubules
162
androgen-binding protein
responsible for the high local testosterone concentration
163
Which two hormones are necessary for spermatogenesis
High local levels of testosterone and FSH
164
Kartagener syndrome
autosomal recessive form of primary ciliary dyskinesia (PCD)
165
Kartagener syndrome etiology
wide variety of mutations that impair ciliary structure or function
166
Kartagener syndrome clinical
triad of situs inversus (due to impaired ciliary movement during embryogenesis), chronic sinusitis, and bronchiectasis (due to impaired mucociliary clearance)
may also see:
Infertility in men (impaired sperm motility) and women (immobility of fallopian tube cilia)
167
Deficiency of the C1 complement component causes
increased susceptibility to encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis) and also predisposes to developing systemic lupus erythematosus
168
cystic fibrosis defect
Epithelial cell chloride channels are defective
169
severe combined immunodeficiency disease (SCID) etiology
Defects in T-cell IL-2 receptors
170
hyper-IgM syndrome etiology
Immunoglobulin gene rearrangement is impaired
171
hyper-IgM syndrome pathology
B cells produce high amounts of IgM but are unable to switch production to other immunoglobulin classes
172
chronic granulomatous disease etiology
NADPH oxidase deficiency
173
Experimental studies
Randomized controlled trial
| Nonrandomized design
174
Randomized controlled trial
Random allocation into treatment & placebo groups
Can determine efficacy of the intervention
175
Nonrandomized design
Nonrandom allocation into treatment & placebo groups
Can determine efficacy of the intervention
176
Observational studies
Cohort
Cross-sectional
Case-control
Case
177
Cohort study
Data gathered from the same individuals over time (longitudinal)
Can assess risk factors or outcomes
178
Cross-sectional study
Data gathered at one point in time
| Can determine prevalence of an outcome in a population
179
Case-control study
Data gathered from individuals with the condition of interest (cases) & compared to individuals without the condition (controls)
180
Case study
Detailed information gathered about one individual (or a small group of individuals)
181
Meta-analysis Review
Data from multiple studies are statistically combined & analyzed
182
Why can HLA gene cluster be treated as an HLA haplotype
HLA genes are clustered within a short region of a single chromosome which results in a low rate of crossover
183
identical HLA match
1/4 chance of inheriting all the same HLA genes
184
haploidentical HLA match
1/2 chance of inheriting half of the same HLA genes
185
HLA mismatch
1/4 chance of inheriting none of the same HLA genes
186
What does the placentation of monozygotic twins depends on?
when zygote division occurs during embryonic development
187
dichorionic/diamniotic monozygotic twins
Early division (days 0-4) can result in monozygotic twins with 2 chorions and 2 amnions which may or may not be fused
188
monochorionic/diamniotic monozygotic twins
Division between days 4-8 is the most common outcome in monozygotic twins and results in 1 chorion (eg, shared placenta) but 2 amnions
189
monochorionic/monoamniotic monozygotic twins
Late division (8-12 days) results in 1 chorion and 1 amnion
190
Most commplications are assocaited with what chorion and amnion presentation and why
A monochorionic/monoamniotic pregnancy is associated with a high fetal fatality rate, due primarily to the increased risk of umbilical cord entanglement
191
monochorionic/monoamniotic conjoined twins
Division occurring after 13 days
192
Dizygotic twins occur due to
fertilization of 2 oocytes by 2 different sperm, can be different sexes, and almost always have 2 chorions and 2 amnions (eg, dichorionic/diamniotic)
193
adenomyosis clinical
regular (ie, cyclic), heavy, painful menses
194
Adenomyosis risk factors
women age >40, and risk factors include multiparity and prior uterine surgery (eg, cesarean delivery)
195
Adenomyosis gross
areas of dark red endometrial tissue (abnormal presence of endometrial glands and stroma) within the myometrium
globular, uniformly enlarged uterus (due to ectopic endometrial glands inducing myometrial hyperplasia and hypertrophy)
196
Why do women with Adenomyosis have painful menses/dysmenorrhea
With each menstrual cycle, the endometrial tissue proliferates and sheds but the bleeding is confined within the uterine wall, causing dysmenorrhea
197
Adenomyosis treatment
Definitive treatment is with hysterectomy
198
Chronic endometritis etiology
intrauterine polymicrobial infection
199
Chronic endometritis clinical
constant pelvic pain with irregular bleeding
200
Chronic endometritis gross
Gross pathology may reveal intrauterine adhesions due to chronic intrauterine inflammation
**Because the disease process is intracavitary, there is no associated uterine enlargement.
201
complete hydatidiform mole clinical
amenorrhea or irregular, first-trimester bleeding
202
complete hydatidiform mole labs
markedly elevated β-hCG levels (ie, >100,000 mIU/mL).
203
complete hydatidiform mole gross pathology
uterine enlargement with numerous edematous intrauterine chorionic villi
204
Endometriosis clinical
dysmenorrhea due to ectopic implantation of endometrial glands and stroma in the abdominopelvic cavity causing chronic pain
Dysuria or suprapubic tenderness and dyschezia (pain with defecation) can be caused by implants on the bladder and rectovaginal septum, respectively. Bowel symptoms commonly worsen with menses
Other common clinical features include an adnexal mass (endometrioma) and cervical motion tenderness
because the ectopic implants are extrauterine, patients do not have uterine enlargement or heavy menses
205
Endometriosis gross
black powder–burn lesions or ovarian cysts
Rectovaginal nodularity is highly characteristic of endometrial implants and fibrosis of the posterior cul-de-sac
206
Uterine leiomyomas (definition and clinical)
benign, uterine smooth muscle cell tumors that can cause regular, heavy menses
207
Uterine leiomyomas gross
irregularly enlarged uterus with discrete tumors
208
Uterine sarcomas
malignant uterine tumors
209
Uterine sarcomas clinical
irregular, postmenopausal bleeding
210
Uterine sarcomas gross
discrete uterine mass.
211
Invasive breast carcinoma gross
irregularly shaped, adherent breast mass most commonly in the upper outer quadrants
212
Invasive breast carcinoma pathology
Malignant infiltration of suspensory ligaments of the breast (ie, Cooper ligaments) causes fibrosis and shortening, leading to traction on the skin with distortion in breast contour.
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most common site of metastasis for breast cancer
Axillary lymph nodes
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metastasis for breast cancer pathophysiology
As malignant cells spread through the lymphatics, they can block cutaneous lymphatic flow, causing peau d'orange (thickened, dimpled skin like an orange peel) and is associated with discoloration and swelling of the breast
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Paget disease of the nipple etiology
Malignant spread of ductal carcinoma to the nipple surface
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Uterus position in endometriosis
The uterus is often immobile and fixed in a retroverted position due to scarring from continued cyclic shedding of ectopic endometrial tissue that has no outlet
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Colorectal hamartomas
benign colonic tumors
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Colorectal hamartomas clinical
may cause abdominal pain due to mass effect
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Endometrial intraepithelial neoplasia etiology
atypical overgrowth of the intrauterine endometrial lining
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Endometrial intraepithelial neoplasia risk factors
women with obesity, chronic anovulation
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Endometrial intraepithelial neoplasia clinical
abnormal uterine bleeding or postmenopausal bleeding
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Invasive urothelial carcinoma clinical
dysuria, but patients typically have painless hematuria
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Serous epithelial ovarian carcinoma clinical
typical presentation is bloating or ascites in a postmenopausal patient with an adnexal mass.
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Posttransplantation lymphoproliferative disorder pathophysiology
Immunosuppression following solid-organ or hematopoietic stem cell transplantation → suppressed cytotoxic T-cell immunosurveillance → Epstein-Barr virus–encoded proteins drive unchecked B-cell growth/expansion
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Posttransplantation lymphoproliferative disorder clinical
Mononucleosis-like symptoms (eg, fever, night sweats, hepatosplenomegaly, lymphadenopathy)
Extranodal mass in approximately 50%
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Posttransplantation lymphoproliferative disorder biopsy
polyclonal or monoclonal B-cell proliferation
large, atypical B cells completely effacing the lymph node architecture
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Posttransplantation lymphoproliferative disorder etiology
proliferation of Epstein-Barr virus (EBV) in donor or host cells due to reduced cytotoxic T-cell immunosurveillance from high dose immunosuppressive therapy.
228
Risk factors for cervical cancer
```
Infection with high-risk HPV strains (eg, 16, 18)
History of sexually transmitted diseases
Early onset of sexual activity
Multiple or high-risk sexual partners
Immunosuppression
Oral contraceptive use
Low socioeconomic status
Tobacco use
```
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neonatal Graves disease etiology
Transplacental transfer of TSH receptor–stimulating antibodies in a mother with Graves disease
230
neonatal Graves disease clinical and labs
tachycardia and irritability, and laboratory evaluation would show high T4 and low TSH
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Polycystic ovary syndrome clinical
Androgen excess (eg, acne, male pattern baldness, hirsutism)
Oligoovulation or anovulation (eg, menstrual irregularities)
Obesity
infertility
Polycystic ovaries on ultrasound
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Polycystic ovary syndrome labs
↑ Testosterone levels
| ↑ Estrogen levels leading to a LH/FSH imbalance
233
Polycystic ovary syndrome pathophysiology
FSH remains low relative to LH, there is no maturation and release of a single, dominant ovarian follicle (ie, anovulation). Instead, multiple, smaller follicles accumulate fluid to cause the classic appearance of bilateral, enlarged, polycystic ovaries
234
atrophic endometrium labs
low estrogen (eg, menopause)
235
Cushing syndrome etiology
cortisol excess, usually due to a hyperfunctioning adrenal adenoma (which causes compensatory contralateral, not bilateral, adrenal atrophy) or an ACTH-producing pituitary adenoma
236
Polycystic kidney disease inheritance
inherited condition with juvenile and adult forms
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Polycystic kidney disease clinical
hypertension, flank pain, hematuria, and renal insufficiency
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Bradykinin
component of the kinin system. It is a short-lived peptide that causes vasodilation, increases vascular permeability, stimulates endothelial smooth muscle dilation, and mediates pain.
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Erythropoietin
growth factor for erythrocyte precursors in the bone marrow. It is produced by peritubular cells of the kidneys in response to hypoxia
240
Leukotriene B4
metabolite of arachidonic acid. Its main function is to stimulate neutrophil migration to the site of inflammation.
241
Platelet-activating factor
released by endothelium, platelets, and immune cells, and is involved in leukocyte function (eg, endothelium attachment, phagocytosis, degranulation), platelet stimulation, and changes to vascular tone and permeability.
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Thromboxane A2
one of the products of the cyclooxygenase pathway. It is synthesized by platelets and causes platelet activation and aggregation. It does not cause erythrocyte aggregation or rouleaux formation.
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Protein synthesis process
1. Transcription of DNA into pre-mRNA within the nucleus
2. Posttranscriptional modification (ie, pre-mRNA processing), including splicing of introns and the addition of a 5' cap and poly-A tail
3. Translation of mRNA to protein at the ribosomes
4. Folding of the amino acid chain into a protein structure
5. Posttranslational modification and trafficking to the correct destinations
244
Inclusion cell (I-cell) disease
defect in posttranslational modification in the Golgi body where defect in a phosphotransferase enzyme prevents phosphorylation of mannose (aka tagged with mannose-6-phosphate)
Lysosomal acid hydrolases are therefore transported inappropriately to the extracellular space, causing an increase in serum concentration and a decrease in intracellular concentration
Without acid hydrolases to degrade cellular debris within lysosomes, the waste products (eg, mucolipids, mucopolysaccharides) accumulate and form inclusion bodies characteristic of the disease.
245
I-cell disease clinical
skeletal abnormalities (eg, coarse facial features), developmental delay, cloudy corneas, and recurrent respiratory infections. I-cell disease is generally fatal in childhood.
246
DNA methylation
silences gene transcription so that the affected protein would be completely absent
247
pathologic example of DNA methylation
inhibition of tumor suppressor genes as a mechanism for cancer development.
248
cystic fibrosis etiology
defect in CFTR protein folding resulting in abnormal protein functioning
249
Splicing mutations
result in inappropriate removal of exons or persistence of introns; this creates aberrant mRNA that is presented for translation and results in production of an abnormal protein
250
ultraviolet light exposure causes what change in DNA?
Pyrimidine dimers are formed in DNA as a result of ultraviolet light exposure. They are recognized by a specific endonuclease complex that initiates the process of repair by nicking the damaged strand on both sides of the pyrimidine dimer. The damaged segment is then excised, and replacement DNA is synthesized by DNA polymerase
251
pyrimidine dimers
formation of abnormal covalent bonds between adjacent thymine or cytosine residues
252
xeroderma pigmentosum etiology
Mutations that impair the components involved in nucleotide excision repair
253
xeroderma pigmentosum clinical
severe photosensitivity and the development of skin cancers at a young age.
254
ionizing radiation (Xrays and gamma) exposure causes what change in DNA? and how can this be fixed?
double-strand DNA breaks. The fractured ends can be joined by nonhomologous end joining
255
Deamination of DNA bases etiology and corrected by?
can occur spontaneously or secondary to chemical exposure. These errors are corrected by base excision repair
256
base excision repair process
abnormal bases are recognized and removed by specific glycosylases without disruption of the phosphodiester backbone. The apurinic and apyrimidinic residues are then removed by specific endonucleases and replaced with the correct base by DNA polymerase.
257
Vesicovaginal fistula defintion and etiology
abnormal connection between the bladder and vagina that most commonly occurs due to bladder injury from surgical or obstetric complications
258
Vesicovaginal fistula clinical
continuous urinary dribbling rather than intermittent urinary leakage, and pelvic examination shows leakage of urine from the vagina (not the urethra)
259
intraductal papilloma clinical
unilateral, bloody nipple discharge with no associated breast masses, skin changes, or axillary lymphadenopathy
**most common cause of pathologic nipple discharge
the bloody discharge results from twisting of the vascular stalk of the papilloma in the duct.
260
intraductal papilloma histology
epithelial and myoepithelial cells lining fibrovascular cores forming papillae within a duct or cyst wall
261
Vaginal adenosis
persistence of glandular columnar epithelium in the vagina and is a precursor for clear cell adenocarcinoma of the vagina. Female offspring exposed to diethylstilbestrol in utero are at increased risk and may present with vaginal discharge or vaginal cysts/fleshy colored lesions.
