2. Dermatologic manifestations of systemic disease
(e.g. neoplasia, inflammatory bowel disease, meningococcemia, systemic lupus
erythematosus)
From
various sources:
|
Café au lait spots |
Neurofibromatosis |
|
hyperpigmentation |
Addison’s disease |
|
Koplik spots |
measles |
|
Erythema chronicum migrans |
Lyme disease |
|
myxedema |
Hypothyroidism |
|
Palpable purpura on
legs/buttocks |
Henoch-Schonlein purpura |
|
Port wine stain |
hemangioma |
|
Rash on palms and soles |
Secondary syphilis
Rocky Mountain spotted
fever meningococcemia |
|
Malar rash, discoid rash |
Lupus (SLE) |
|
“slapped cheeks” |
Fifth disease (erythema
infectiosum) |
|
Osler’s nodes, Janeway
lesions |
Bacterial endocarditis |
|
Erythema marginatum
(distinctive migratory and transient pink rash with pale centers) |
Rheumatic fever |
|
Raynaud’s phenomenon |
Buerger’s disease,
CREST (scleroderma) |
|
Caput medusae |
Portal HTN |
|
Erythema nodosum, pyoderma
gangrenosum |
Ulcerative colitis |
|
|
|
|
|
|
|
|
|
|
|
|
From lecture (12/21/00):
Neoplasia
|
Cutaneous metastasis
|
-75% are first sign of
extranodal spread -common primaries: breast,
lung, GI and skin -firm papules/nodules, often
bound down; ulcers |
|
Leukemia cutis |
-localized or disseminated
skin infiltration by leukemic cells -diffuse, small pinkish,
non-tender papules -herald presence of leukemia
cells in peripheral circulation |
|
|
Paraneoplastic pemphigus |
-autoimmune blistering
condition affecting skin and mucosa -indirect
immunofluorescence: binding to simple, columnar and transitional epithelia (chicken wire staining) -vermillion border
involvement is characteristic -associated w/ CLL, large
cell lymphoma, non-Hodgkin’s, Waldenstrom’s macroglobulinemia |
|
|
Bullous neutrophilic
dermatosis |
-rapidly expanding painful,
ulcerative nodule -looks like bad infection,
but aseptic w/ hemorrhagic border -lesions form after trauma
(Pathergic response) -associated w/ lymphoreticular
system malignancies -treat w/ steroids or
immunosuppressive agents |
|
|
GI |
Peutz Jehgers
|
-autosomal dominant
polyposis w/ hyperpigmented macules -hyperpigmentation of lips,
buccal mucosa, palms/soles, periorbital -hamatomatous polyps in
small intestine mainly -Sx: recurrent attacks of
severe abdominal pain (intussusception, obstruction, rectal prolapse, GI
bleeding) -rarely associated w/ gondal
tumors, breast carcinoma |
|
Acrodermatitis
enteropathica |
-disorder of zinc
absorption – genetic or
acquired -triad: acral dermatitis
(hands/feet, face, anogenital), alopecia, diarrhea -dry, scaly eczematous
patches and plaques |
|
|
Glucagonoma syndrome |
-excessive production of
glucagons by a-cell tumor of pancreas -lesions w/ central clearing
and blistering/crusting edges -periorificial and
intertriginous dermatitis/erythema -glossitis and angular
chelitis also seen |
|
|
Gardner’s syndrome |
-autosomal dominant
intestinal (colonic) polyposis -high rate of malignant
transformation -multiple epidermoid cysts,
esp of face, scalp and trunk -osteomatosis of maxilla,
mandible and cranial bones -fibrous tumors of skin and
subcutaneous tissue |
|
|
Muir-Torre syndrome |
-sebaceous tumors most often
on face and trunk -assoc. w/ visceral
neoplasms, esp colon, also larynx
& endometrium |
|
|
Endocrine & Metabolic |
Necrobiosis lipoidica
diabeticorum |
-sharply circumscribed
atrophic plaques w/ yellowish-brown color -classical location:
anterior and lateral surfaces of lower legs -2/3 have overt diabetes
mellitus |
|
Pretibial myxedema |
-bilateral indurated plaques
and nodules (orange peel-like) -pretibial region of lower
extremities -occurs w/ Grave’s
disease, recovery from
“thyroid storm” |
|
|
Acanthosis Nigrican |
-diffuse velvety thickening
and hyperpigmentation -typically on axilla, other
body folds, knuckles -associated w/ endocrine
disorders (IDDM, acromegaly, Cushing’s, Addison’s), drugs, paraneoplastic (adenocarcinoma) |
|
|
Cowden’s disease |
-multiple wart-like lesions
around mouth, nose, ears -multiple popular lesions
(“cobblestones”) on mucosal membranes -increased risk of breast
and thyroid cancers |
4. Renal failure: acute versus chronic, features of
uremia
Acute |
Chronic |
|
-quicker onset -usually reversible |
-progressive -usually irreversible w/
scarring -leads to end stage renal
disease |
Causes of renal failure
|
prerenal |
renal |
postrenal |
|
-hypovolemia -cardiac failure -hepatorenal syndrome -NSAIDs -ACE inhibitors |
-vascular disorders -glomerulonephritis -interstitial nephritis -tubular necrosis |
-extrarenal obstruction -bladder rupture |
Uremia – signs and symptoms of toxin accumulation when
kidney fails. Clinical characteristics:
BRS Pathology, lecture
(12/6/00)
5. Acid-base disturbances, including renal tubular
acidosis
|
|
pH |
PCO2 |
[HCO3-] |
causes |
Compensatory response |
|
|
Respiratory acidosis |
< 7.4 |
> 40 mmHg |
|
COPD, airway
obstruction |
Renal [HCO3-]
reabsorption |
|
|
Respiratory alkalosis |
> 7.4 |
¯ < 40 mmHg |
¯ |
High altitude,
hyperventilation |
Renal [HCO3-]
secretion |
|
|
Metabolic acidosis (check anion gap) |
¯ < 7.4 |
¯ < 40 mmHg* |
¯ |
DKA, diarhhea, lactic
acidosis, salicylate OD, acetazolamide OD, renal failure |
hyperventilation |
|
|
Metabolic alkalosis |
¯ > 7.4 |
> 40 mmHg* |
|
vomiting |
hypoventilation |
|
|
* with compensation |
|
|||||
|
|
|
|||||
Metabolic acidosis: Anion gap = Na+ - (Cl- + HCO-3)
= 8-12 mEq/L
|
Elevated |
Normal |
Decreased |
|
|
|
-sodium concentration falls
while the chloride plus bicarbonate concentrations are unchanged -serum sodium concentration
remains normal while the serum chloride plus bicarbonate concentrations are
increased |
|
-methanol -uremia -diabetic ketoacidosis -paraldehyde -phenformin -Iron -INH -lactic acidosis -ethanol, ethylene glycol -salicylates (MUDPILES) |
I. Renal Causes A. Bicarbonate loss Proximal renal
tubular acidosis (RTA), type II (can be part of Fanconi’s Syn) Dilutional
acidosis Carbonic
anhydrase inhibitors Primary
hyperparathyroidism B. Failure of bicarbonate
regeneration Distal RTA, type
I Distal RTA, type
IV Diuretics:
amiloride, spironolactones II. Gastrointestinal
Causes Diarrheal states Small bowel drainage Ureterosigmoidostomy III. Acidifying Salts Ammonium chloride Lysine hydrochloride Arginine hydrochloride Parenteral hyperalimentation |
-multiple myeloma (IgG) -hypoalbuminemia -rarely: lithium
intoxication, hypermagnesemia, and hypercalcemia |
Lecture (11/29/00),
Cecil’s
6. Wound repair
-begins
in early stages of inflammation
-initiated
by liquefaction and removal of dead cellular material and other debris
-highly
vascular, newly formed connective tissue consisting of capillaries and
fibroblasts
-fills
defects created by liquefaction of cellular debris
-collagen
produced by fibroblasts progressively increases
-tissue
becomes progressively less vascular and cellular
-contraction
of wound occurs, can result in deformity of original structure
BRS Pathology; Cecil’s
8. Menstrual disorders (e.g. amenorrhea, abnormal
uterine bleeding)
·
Average age of menarche
is 12 yrs; 9-16 is normal range
·
Cycle averages 28 days: 14 days of follicular phase,
ovulation and 14 days of luteal phase
o
Normal range is 25-34
days
o
Polymenorrhea: cycle less that 21 days
o
Oligomenorrhea: cycle longer than 45 days
·
Normal menstral flow
lasts 5 days; range is 2-8 days
o
Hypomenorrhea: very short and scant menses
o
Hypermenorrhea/Menorrhagia:
long periold of flow or heavy amount
of fluid
o
40 ml average flow. >
80 ml abnormal. Ask about # and frequency of pad/tampon use instead
·
Symptoms associated w/
normal menstration
o
Mittleschmertz (middle pain): small pain sometimes felt during
ovulation. May be from abdominal irritation from fluid release @ ovulation.
o
Molimina: the variety of symptoms experienced before menstration.
Includes weight gain, breast tenderness, edema, and irritability. Pre-Menstral
Syndrome (PMS) if exaggeraged or troublesome.
o
Dysmenorrhea: menstral cramping. Usually mild, well treated w/
NSAIDs. In some women, cramping is excessive and limits activity.
|
Compli-cations of pregnancy |
-one of most common causes
of abnormal bleeding -1st trimester
bleeding causes: ectopic pregnancy, miscarriage (see below), trophoblastic
disease Threatened abortion: uterine bleeding, but cervix remains closed Inevitable abortion: uterine bleeding and dilated cervix Incomplete abortion: uterine bleeding where some by not all tissue passed.
Often requires surgical intervention (D&C) Complete abortion: uterine bleeding with passage of all uterine
contents (Missed abortion: no viable pregnancy, seen on US, but no abnormal
S/Sx) |
||
|
Organic lesions |
Leiomyomas
|
-distort and exaggerate
surface area of the endometrium
-cause heavier bleeding at
usual time of menses |
|
Cervical carcinoma
|
-irregular,
unpredictable bleeding
|
||
Vulvular/vaginal carcinoma
|
-irregular,
unpredictable bleeding
|
||
Endometrial/ endocervical polyps
|
-benign overgrowths of
endometrium or cervical epithelium
-spotting (inter-menstral
bleeding), post-coital bleeding |
||
Pelvic infection
|
-all types of infections
can cause (cervicitis, endometritis, PID)
-usually between menstral
cycles |
||
|
Hormonal disorders |
Disruption in HPO Axis can cause hormonal imbalance -causes intermittently
shedding endometrium -normal physiology:
ovulation is critical to normal pattern of bleeding. Estrogen in follicular
phase lead to endometrial proliferation. Progesterone in luteal phase (and
decreased estrogen) allows normal endometrial shedding -estrogen w/o progesterone -> constant state of
proliferating endometrium, starts to partially and intermittently shed,
causing abnormal bleeding |
||
|
Anovulaotry states or intermittently ovulatory states -seen near extremes of
menarche and menopause (beginning and end) -lack of ovulation causes
irregularly paced periods and irregular patterns of endo sloughing |
|||
Exogenous estrogen use w/o progesterone
-usually seen with estrogen
replacement or oral contraceptives -balance exogenous estrogen
w/ exogenous progesterone to provide normal bleeding pattern |
|||
|
Constitu-tional disorders |
Bleeding disorders
|
-heavy menses can be
presenting complaint of young women w/ von Willebrand’s Disease |
|
|
Hypothyroidism |
-can lead to anovulation and
abnormal bleeding |
||
|
Hyperprolactinemia |
-can cause amenorrhea -can be caused by
prolactinoma, breast feeding, or certain meds (e.g. antipsychotics) |
||
|
Liver disease |
-severe disease: hormones
not degraded properly -> imbalanced hormone levels and abnormal bleeding
patterns |
||
DIAGNOSIS AND MANAGEMENT OF
ABNORMAL UTERINE BLEEDING
|
General |
H&P: very important in all patients Labs: Pap smear, CBC, pregnancy test, endometrial biopsy,
hormonal testing (estrogen, progesterone, FSH, LH, prolactin, etc) |
|
Adolescent |
Anovulation: often due to immaturity of hypothalamic pituitary
axis -tx: birth control pills to
exogenously impose regular cycles, self-regulation occurs in time Pregnancy: ask (confidentially) if they are sexually active Pelvic exam: on kids and non-sexually active can be traumatic.
Use ultrasound instead. Blood dyscrasias: can be cause of primary heavy bleeding problems Management for most adolescent disorders is hormonal to
regulate cycle Endometrial sampling is usually not indicated for this age
(hyperplasia/neoplasia rare) |
|
Childbearing/
Reproductive age |
Pregnancy complications
and organic lesions: check TSH and
prolactin (Sx can be subtle) Endometrial biopsy or D&C:
indicated for age 30-35 due to risk of hyperplasia/malignancy Management is primarily hormonal manipulation (combo or
progesterone pill) NSAIDs for menorrhagia for pain and reducing bleeding (¯ prostaglandin ® ¯ bleeding) Surgical intervention: hysterectomy or endometrial ablations
to control bleeding; also removal of fibroids |
|
Peri-menopausal |
Rule out
malignant/pre-malignant conditions of cervix and uterus: risk with age -Pap smears and endometrial
biopsy become important Hormonal management ONLY if pt has non-malignant condition -Oral contraceptives NOT
used for women smokers > 35 (risk of clotting problems) Surgical tx indicated if medical tx fails -D&C: primarily diagnostic, also therapeutic for some
endometrial polyps -Hysterectomy: therapeutic for many bleeding etiologies -Endomentrial ablation: to remove endometrium and control bleeding Transition from normal cycling to menopause: frequency often
decrease, can increase - need to rule out if just transition or pathology
(e.g. cancer) |
Primary amenorrhea
|
-Definition: lack of menses
by age 16 -takes ~ 2 yrs from start of
growth of pubic hair to start of menses |
Secondary amenorrhea
|
-Definition: cessation of
menses for a period of time (usually 3 cycles) -pregnancy or hormonal imbalance etiologies most likely -causes: disruption of
HPaxis, anorexia, excessive exercise, some drugs, stress |
|
Differential diagnosis |
Physiologic: pregnancy, breastfeeding, menopause
|
|
Anatomic: anatomic dysfunctions on any level of system -Uterovaginal anomalies,
ovarian anomalies -pituitary dysfuction - due
to tumors, irradiation, surgery or Sheehan’s syndrome (infarction) -hypothalamic or CNS -Hypothyroidism: TSH also stimulates prolactin release |
|
Diagnosis |
-Primary amenorrhea: where is pt in rest of sexual
development (breast buds, axillary/pubic hair?) -Excessive exercise: can
become hypoestogenic ® reduced bone density -Embryology: lower 2/3 of
vagina formed from urogenital sinus, upper 1/3 from fused mulerian ducts. If
structures don’t form correctly or fuse properly, pt can have
imperforate hymen or vaginal atresia. |
|
Imperforate hymen: pts menstrate but don’t experience external
bleeding -experience cyclic symptoms
of menstration, but present w/ 1° amenorrhea -PE: imperforate hymen that
is usually bulging outward w/ blood -Tx: correct surgically by
making X-shaped incision, will menstrate normally -higher risk for endometriosis
due to retrograde menstral flow |
|
|
Congenital absence of
uterus and vagina: failure of
mulerian ducts to form properly. -have functional ovaries and
normal hormonal function -Associated renal and pelvic
abnormalities -blind vaginal dimple
(remnant from urogenital sinus) -create vagina by stretching
pouch w/ direct pressure using dilator over several months -once sexually active,
dilator no longer needed (use periodically if not) |
|
|
Androgen insensitivity: genotypically male, phenotypically female; lack of
testosterone receptor -have normal breast
development, sparse axillary/pubic hair and a vaginal dimple -have testes, not ovaries
– need to be removed surgically due to risk of malignancy -aka testicular
feminization or male
pseudohermaphroditism (think Jamie Lee Curtis) |
|
Turner’s Syndrome: 45 XO or mosaic genotype
-characteristic webbed neck,
shield chest, cubitus valgus, sexual infantilism -do not have functioning
ovaries, do no menstrate properly |
|
Polycystic Ovarian Syndrome: obesity, hirsutism, and acne are
classic triad w/ amenorrhea
-tend to be hyperandrogenic,
exact etiology unknown -anovulation and
oligomenorrhea or amenorrhea -begin to put on weight in
teens or early 20’s -losing weight helps
condition, but difficult for pts to do (insulin resistance contributes?) |
|
|
Work-up |
Ultrasound: used to examine ovaries |
Labs:Serum prolactin and TSH, pregnancy test, karyotyping,
androgen levels, FSH/LH
|
|
|
MRI: used to image pituitary to look for tumors (e.g.
prolactinoma) |
|
|
Progesterone challenge: adminster progesterone for 5 days, followed by
withdrawal of progesterone. Induces menses if uterus and outflow tracts are
normal |
|
|
Endometrial sampling: using biopsy or D&C to check if lining of
uterus is appropriately proliferative or secretory, presence of
hyperplasia/carcinoma |
|
Treatment
|
-dependent on cause Hormonal imbalance: cyclic progestational agents to mimic luteal phase
and regulate menstration or complete exogenous regulation w/ combo OCPs Goals: correct hypoestrogenism, prevent endometrial hyperplasia,
correct elevated prolactin levels -can include surgical
“reconstruction”, hormonal manipulation, nutrition/exercise
counseling |
Lecture (4/16/01)
9. Cell injury and death
·
Ischemic cell injury
o
Causes: Obstruction of
arterial blood flow, Anemia, CO poisoning, decreased perfusion, poor
oxygenation of blood
o
Early stages –
mitochondria affected, decreased oxidative phosphorylation and ATP synthesis
§
Failure of cell membrane
pump – hydropic change, swelling of ER, swelling of mitochondria
§
Disaggregation of
ribosomes and failure of protein synthesis
§
Stimulation of
phosphofructokinase activity – increased glycolysis, lactate,
acidification
o
Late stages –
membrane damage, reversible
§
Myelin figures –
whorl-like, from damaged membranes
§
Cell blebs – from
disorderly fxn of cytoskeleton
o
Cell death
§
Irreversible damage to
mito and cell membranes – massive Ca++ influx
§
AST, CPK, and LDH into
blood are indicators of injury to heart muscle
§
Vulnerability varies w/
tissue type: neurons (3-5 min), myocardial cells and hepatocytes (1-2 hrs),
skeletal muscle (many hrs)
·
Free radical injury
o
Generation by normal
metabolism, oxygen toxicity (e.g. ARDS, retrolental fibroplasias), ionizing
radiation, drugs and chemicals, reperfusion after ischemic injury
o
Free radical degradation
occurs by intracellular enzymes (glutathione peroxidase, catalase, superoxide
dismutase), endogenous substances (ceruloplasmin, transferring), spontaneous
decay
·
Chemical cell injury (e.g. liver cell membrane damage by CCl4)
o
Processed by P-450s to
make highly reactive CCl3·
o
CCl3· initates lipid peroxidation of intracellular
membranes
§
Disaggregation of
ribosomes -> decreased protein synthesis, accumulation of intracellular
lipids (fatty change)
§
Plasma membrane damage
-> cellular swelling, massive influx of Ca++, mitochondrial
damage
·
Necrosis
o
Coagulation necrosis
§
Sudden cutoff of blood
supply to organ (esp. heart, kidney)
§
Preservation of tissue
architecture in early stages
§
Increased cytoplasmic
eosinophilia due to protein denaturation
§
Marked nuclear changes
·
Pyknosis – chromatin clumping, shrinking w/ increased
basophilia
·
Karyorrhexis – fragmentation
·
Karyolysis - fading
·
Disappearance of
stainable nuclei
o
Liquefaction necrosis
§
Softening of tissue
§
From ischemic injury to
central nervous system by autolysis, suppurative infections
o
Caseous necrosis
§
Combine coagulation and
liquefaction necrosis
§
Cheese-like on gross
exam
§
Amorphous eosinophilic
appearance
§
Part of granulomatous
inflammation (e.g. TB)
o
Gangrenous necrosis
§
Most often lower
extremities or bowel
§
Secondary to vascular
occulusion
§
“Wet” when
complicated by infective heterolysis and liquefaction necrosis
§
“Dry” when
mostly coagulation necrosis w/o liquefaction
o
Fibrinoid necrosis
§
Immune-mediated vascular
damage
§
Deposition of
fibrin-like proteinaceous material in arterial walls
o
Fat necrosis
§
Traumatic: following severe injury to tissue w/ high fat
content (e.g. breast)
§
Enzymatic: complication of acute hemorrhagic pancreatitis
·
Pancreatic enzymes
diffuse into tissue, digest parenchyma
·
Liberated fatty acids
form calcium salts (saponification)
·
Vessels eroded ->
hemorrhage
o
Apoptosis – programmed cell death
§
Shrinkage and increased
acidophilic staining
§
Physiologic process for
removal of cells during embryogenesis, programmed cell cycling
BRS Pathology
10. Malabsorption (e.g. celiac sprue, bacterial
overgrowth, disaccharide deficiency)
Disease |
morphology |
other |
|
Celiac sprue |
-Flat mucosal surface w/
villous atrophy -increased lymphocytes and
plasma cells in lamina propria |
-Immune-mediated gluten
sensitivity -associated w/ HLA-B8 and HLA-DW3 -can lead to B-cell
lymphoma in small intestine -weight loss, weakness,
diarrhea -pale, bulky, frothy
foul-smelling stool |
|
Tropical sprue |
-histological finding vary
(can be like celiac) |
-probable infectious origin -often responds to
antibiotics |
|
Whipple’s disease |
-PAS-positive macrophages
in intestinal mucosa -bacteria-like inclusions
by EM |
-may affect any organ |
|
Disaccharidase deficiency |
-no histological changes |
-deficiency in brush border
disaccharideases -Lactase deficiency: milk
intolerance, most frequent -flatus, osmotic diarrhea |
|
Bacterial overgrowth |
-colon-like growths and
populations of bacteria in small bowel |
-occurs in areas of stasis
(causes: surgery, fistula, diverticuli, strictures, etc) |
|
abetalipoproteinemia |
-circulating acanthocytes
suggest diagnosis |
-hereditary deficiency of
apoprotein B |
|
Intestinal lymphangiectasia |
-generalized dilation of
small intestinal lymphatics |
-gastrointestinal protein
loss -hypoproteinemia,
generalized edema |
|
Chronic pancreatitis |
-destruction and fibrosis
of pancreas |
-impaired secretion of
pancreatic enzymes, fluid, HCO3 -often due to long-standing
alcohol use -weight loss, poor
appetite, oily bulky stools, edema, hypoproteinemia |
BRS Pathology; lecture
(1/10/01)