Pathology - part 2 Respiratory, GI, etc Flashcards
PH (pulmonary hypertension)
cause, mechanism, patho,
mean PA pressue > 25/30 mm Hg at rest/exercise
mechanism 2° PH: respiratory acidosis/hypoxemia → vasoconstriction PAs
MCC 2° PH: left-sided valvular disease
Patho: atherosclerosis in main PAs
MC sym: exertional dyspnea
tapering PAs/RVH (right ventricular hypertrophy) on chest X-ray: cor pulmonale (= PH + RVH, 肺心病）
Goodpasture syn
cause? presentation?
Ab attack basement membrane in pulmonary cap and glomerular cap (type II hypersensitivity)
hemoptysis (咯血）followed by renal failure
RLD (restrictive lung disease)
defination? cause? 表现？
defination: ↓ TLC (total lung capacity)
cause: chest wall disorders (ie: kyphoscoliosis, mesothelioma, obesity, acute/chronic ILDs - interstitial lung diseases. ILD的一种，idiopathic pulmonary fibrosis: most MCC of RLD; sarcoidosis)
dry cough, inspiratory crackles (湿罗音）in lower lung fields, exertional dyspea
favor shallow, fast breath to ↓ work of breathing
Pathogenesis of interstitial fibrosis? Dx?
earlist manifestation: alveolitis [leukocytes release cytokines → fibrosis] → interstitial fibrosis
↓ compliance (↓ expansion during inspiration)
↑ elasticity (↑ recoil during expiration
Pulmonary function test: all volumes and capacities are equally ↓; normal to ↑ FEV1/FVC ratio (normal is 80% = 4L/5L), respiratory alkalosis (PCO2 < 33 mmHg）， ↓PaO2
X-ray: diffuse bilateral reticulonodular infiltrates
silicosis: X-ray特征改变？
胸片见egg-shell calcification in hilar nodes
MC occupational disease
opacities contain collagen and quartz (highly fibrogenic)
↑ risk for lung cancer/TB [differentiate: CWP (coal worker’s pneumoconiosis): no risk for lung cancer/TB]
if lung is encased, likely Rx?
mesothelioma (arise from pleura serosa)
no relationship with smoking
sarcoidosis:
etio? patho? Dx?
immune regulation disorder: CD4 Th cells interact with unknown Ag
noncaseating granulomas: Dx is exclusion (rule out other granulomas diseases)
lung is the target organ: dyspnea is the MC sym [patho: granulomas contain multinucleated giant cells]
UW case: 35-yr black woman, arthralgias+tender, deep nodules on legs, hepatomegaly (scattered granulomas), chest X-ray: enlarged hilar lymph nodes, serum ACE ↑[note: important lab for sarcoidosis]
Caplan syn?
cavitating rheumatoid nodules in the lung + pneumoconiosis
emphysema 肺气肿
patho?
how can smoking produce emphysema?
MCC: smoking; α1-AAT (α1 antitrypsin: antielastase) deficiency
patho: ↑ compliance, ↓ elasticity (能张开，但是无法recoil)
inbalance between elastase vs. antielastases; free radicals vs. GSH
cigarette smoke: chemotactic to neutrophils and macrophages ➞ release free radicals ➞ inactivate AAT/GSH
分为centriacinar vs. panacinar:
centriacinar: destruction of distal terminal bronchioles /upper lobe; panacinar: entire respiratory unit, lower lobe, no α1-globulin peak on serum protein electrophoresis
early dyspnea + late hypoxia (take time to destruct respiratory unit)
X-ray: ↑ hyperlucency, ↑ anterior-posterior diameter, vertically oriented heart, depressed diaphraghms
↑ TLC, RV; ↓ FEV1/FVC
↓ PaO2, normal to ↓ arterial PCO2 (pink buffer)
bronchial asthma
extrinsic (most, autoimmune) vs intrinsic (nonautoimmune)
extrinsic: type I HSR: allergen stimulates CD4 TH2 cells ➞ release IL4, IL-5 ➞ IL-4 stimulates isotype switching to IgE (release histamine, etc from mast cells）, IL-5 stimulates production and activation of eosinophils （major basic protein and cationic proteins to damage epithelial cells)
other mediators: leukotrienes (LTC-D-4， acetylcholine)
intrinsic (ie, viral infection, etc): normal IgE, negative skin tests to allergens
Bronchial asthma: alkalosis or acidosis?
initially: respiratory alkalosis (work hard to expell air, 过度通气）
If bronchospasm is not relieved, progress into respiratory acidosis
[normal pH or acidosis: indicates need for intubation !!!!]
FEV1 is the best measure of severity
MCC of bronchiectasis?
In US: CF
worldwide: TB
CF: cause? symptoms?
AR, MC fatal heretidary disorders in whites in US
3-nucleotide deletion in chr#7， coding for Phenylalanine: mutation causes defective protein folding in CFTR (CF transmembrane conductance regulator)➞ degraded in Golgi
CFTR is regulated by cAMP/ATP
CF: loss of NaCL in sweat (for Dx) /luminal secretion (dehydrated, thickened secretion)
nasal polyps in children, respiratory infections (MCC death in CF), chronic pancreatitis producing malabsorption, type I DM), infertility in males,
3 (patho/histological) types of pneumomia?
- bronchopneumonia: locally, involve lower or right middle lobe; pathy areas of consolidation
- interstitial pneumonia: inflammatory infiltration is confined to the alveolar walls
- lobar pneumonia: involve an entire lung lobe
stages and patho characteristics of lobar pneumonia?
- congestion (充血）：< 24 hrs [vascular dilation, alveolar exudate contains mostly bacteria], affected lobe is red, heavy and boggy
- red hepatization: 2-3 days [alveolar exudate contains RBCs, neutrophils and fibrin]; red, firm lobe, liver-lie consistency
- grey hepatization: 4-6 days [RBCs distegrate, alveolar exudate contains neutrophils and fibrin]
- resolution: enzymatic digestion of the exudate, restore the normal architecture
work of breathing change in obstructive vs. restrictive pulmonary disease?
obstructive (asthema, COPD): compliance ↓, airflow resistance ↑: favor lower rate/higher TV (tidal volumes): show, deep breath
restrictive (fibrosis, asbestosis): elasticity ↓, elastic resistance ↑: favor faster rate/low TV: fast, shallow breath
most sensitive test to rule out asthma?
Bronchial challenge test: test bronchial hypersensitivity. Give an aerosolized bronchoconstrictive substance required to produce a 20% ↓ in FEV1
usually use Methacholine
this test is sensitive but not specific. Used to exclude asthma
complication of give premature newborns concentrated O2?
retinopathy of prematurity: concentrated O2 ⇒ VEGF ↑ ⇒ abnormal retinal neovascularization
asbestosis: sym? light microscope? cancer related?
formation of fibrocalcific plaques on the parietal pleura, Subsequent diffuse pleural thickening and fibrosis of the lower lung lobes,
clinic: dyspnea, ↓ lung volumes (restrictive lung disease)
light microscope: interstitial fibrosis, asbestos bodies (ferruginous bodies， 铁锈色体): asbestos fibers coated with protein-iron matrix
risk for bronchogenic carcinoma ↑↑↑, MC cause of death; the 2nd leading cause of death is mesothelioma
TB: 病原体隐藏在what kind of cells? virulence factor? 肺部病理表现（分为primary vs, reactivation TB)?
organisms reside in phagasomes of alveolar macrophage! Produce ‘cord factor” (a protein to prevent fusion of lysosomes with phagosomes)
[note: humoral immunity plays no role in TB, because TB is an intracellular parasite in macrophages！】
TB特征：strict aerobe (like to be in upper /apex lobe), acid-fast 抗酸
primary TB: upper part of lower lobes, or lower parts of upper lobes; Ghon focus (= casecous necrosis: yellow-tan subpleural granuloma); Ghon complex (冈氏病灶）：caseous necrosis in hilar nodes
secondary (reactivation) TB: in immunosuppressed patients (HIV, corticoids, etc): upper lobe cavitary lesions (due to release of cytokines from memory T cells)
cough, hemoptysis, weight loss;
acid-fast bacillion a sputum culture, cavitary upper love pulmonary lesion on X-ray:
Dx？
reactivation TB
lung cancer histology: ovoid cells smaller than resting lymphocytes, immunostaining positive for chromogranin: Dx?
small cell carcinoma
strongly associated with smoking, centrally located;
round or oval cells with scant cytoplasm and large hyperchromatic nuclei; resemble lymphocytes, but smaller
Goodpasture syn?
IgG directed against basement mem. in pulmonary cap and glomerular ca. (type II HSR)
clinic: hemoptysis followed by renal failure
Churg-strauss syn?
autoimmune medium and small vessel vasculitis.
It usually (but not always) manifests in three stages. The prodromal stage is marked by airway inflammation: almost all patients experience asthma and/or allergic rhinitis; the second stage is characterized by hypereosinophilia: abnormally high numbers of eosinophils, which causes tissue damage — most commonly to the lungs and the digestive tract. The third and final stage consists of vasculitis, which can eventually lead to necrosis and is potentially life-threatening.
Dx: insidious-onset progressive exertional dyspnea, restrictive pulmonary function test, extensive interstitial fibrosis, “honeycomb lung”
Dx: idiopathic pulmonary fibrosis
Kaposi sarcoma口腔累及部分？caused by which virus?
hard palate; HHV-8
Behcet syndrome: cause? clinic? patho?
cause: enviromental + genetic factor (HLA-B51, HLA-B27 associated) 多见于土耳其人，地中海地区
clinic: triad (recurrent aphthous ulcers 口疮, uveitis 眼色素层炎，genital unclers)
patho: immune complex systemic small vessel vasculitis
can be fatal due to aneurysms or severe neurological complications
treatment: antiinflammatory medications, corticosteroids
Wickham striae: associated with?
丘疹表面形成的网状灰色线
squamous dysplasia/SCC
dentigerous cyst: associated with?
3rd molar, ameloblastoma (成釉细胞瘤）
benign tumors of the oral cavity?
squamous papillomas 鳞状细胞乳头状瘤：MC benign tumor in oral cavity
ameloblastoma 成釉细胞瘤）
oral SCC metastasis site?
superior jugular node (tonsillar node)
TE (tracheoesophageal) fistula 气管食管瘘
proximal esophagus ends blindly, and the distal esophagus arises from the trachea.
polyhydraminos (羊水过多；swallowed amniotic fluid can’t be reabsorbed in the small intestine); NB with stomach distention/feeding problem
VATER syn
verterbral abnomalities
A: anorectal
TE: tracheoesophageal fistula
R: renal disease + absent radius
Plummer- Vinson syn
chronic iron deficiency
intermittent dysphagia for solids
due to esophageal web (食管蹼）or stricture （狭窄）
↑ risk for SCC: pre-malignant condition
Zenker diverticulum (憩室）
MC pulsion diverticulum (食管压入性憩室）， mucosa/submucosa, located in upper esophagus, area of weakness is the cricopharyngeus muscle (环咽肌）
painful swallowing, halitosis （口臭）
Dx: surgery
define “Barrett esophagus”? complication?
seen in GERD (Gastro-esophageal reflux disease)
glandular (intestinal) metapliasia in distal esophagus due to acid injury
↑ risk for distal adenocarcinoma, stricture
Boerhaave syn: defination? cause? Dx?
rupture of distal esophagus
caused by retching/bulimia (贪食)/endoscopy (~ 75%)
air in the subcutaneous tissue in anterior mediastinum, crunching sound in physical exam; pleural effusion contains food, acid, amylase
Hematemesis; ↓ BP
Diagnosis: Often can be seen on X-Ray
Achalasia: cause? presentation?
MC neuromuscular disorder of esophagus, ↑ risk for esophageal cancer;
failure to relax LES (low esophageal spinkler): ↓ NO, VIP (vasoactive intestinal peptide)
Autoimmune destruction of myenteric (肠肌层）nerve fibers/inhibitory neurons in myenteric plexus
症状：1)nocturnal regurgitation undigested food; 2)dysphagia for solids + liquids (from High LES Opening pressure and uncoordinated Peristalsis leading to Aperistalsis)
3) chest pain, heartburn
4) nocturnal cough from aspiration
Dx: barium swallow shows “birds-beak”：narrowed esophagogastric junction
MC esophagus cancer in US?
distal adenocarcinoma
Barret esophagus is precursor lesion (not involve smoke)
MC primary esophageal cancer in developing countries?
SCC
MCC: smoke cigarettes
Alcohol abuse, lye strictures
dysphagia for solids + weight loss
tracheal invasion: dry cough + hemoptysis
hoarseness (invasion of recurrent laryngeal nerve)
hypercalcemia (↑PTH)
MCC for hematemesis (呕血，与咯血区别！！）
PUD (peptic ulcer disease)
esophageal varices (静脉曲张）
hemorrhagic gastritis
melena (黑粪症）: cause? indicator of?
Hb converted into hematin (black pigment) by acid，
signify bleed proximal to duodenojejunal junction (controlled by ligament of Treitz)
sign for upper GI bleed
Gastric analysis:分析什么指标？
BAO/MAO ratio (normal is 0.2 ： 1）
BAO： basal acid output (acid output of gastric juice collected via nasogastric tube over 1 hr on an empty stomach
MAO: maximal acid output (acid output collected over 1hr after pentagastrin stimulation)
gastroparesis: cause?
胃轻瘫
↓ stomach motility: autonomic neuropathy (eg: DM)
early satiety (饱满感),vomit undigested food
acute hemorrhagic gastritis: MC cause? clinic findings? treatment?
MCC: NSAIDs; alcohol second
H. pylori
smoking; burns (“Curling ulcers); CNS injury (“Cushing ulcers”)
Clinics: hematemesis, melena, iron deficiency
H. pylori
mechanisms of injury
Type B chronic atrophic gastritis
gram-negative rod; live in the mucus overlying the epithelium of the gastric antrum and fandus; produce urease (convert amino groups in protein to ammonia) - rapid test, turn urea solution (with pH indicator) into pink (pH ↑, due to more alkaline produced: urea converted into CO2 and ammonia)
colonizeds mucous layer, noninvasive
tests:
1) urea breath test: does NOT distinguish active vs. old infection
2) stool Ag test: positive = active infection; negative: no infection
3) gastric biopsy to detect urease: gold standard
H.pylori-associated antral gastritis ➞ somatostatin (inhibit gastrin) -producing antral cells ↓ ⇒ gastrin ↑ ⟹ histamine ↑ ⟹ gastric parietal cells secret more acid
NOTE: acid ⟹ duodenal ulceration, NOT gastric ulceration! H.pylori-associated gastric ulceration results from its destruction of the local mucous layer and the local inflammatory response; normal acid level is sufficient to cause ulcer if the mucus is degraded.
PUD (peptic ulcer disease): MCC?
MCC: H.pylori
duodenal > gastric
duodenal ulcers never malignant (do not need to biopsy)
gastric ulcers: small percentage malignant ➞ biopsy
4 layers in sequence are noted in histologic section of ulcers: necrotic debris ➞ inflammation (predominance of neutrophils) ➞ granulation tissue ➞ fibrosis
ZE syn (Zollinger-Ellison syn)
malignant tumor: ↑ gastrin, ↑ acid (loss of negative feedback)
duodenum MC site (NOTE: in distal, not proximal duodenum, different from most duodenum ulcer), pancreatic islets 2nd; single or multiple ulcers
PUD+diarrhea, family history of MEN type I syn (parathyroid or pituitary tumors), or PUD without H.pylori or history of NSAIDs
epigastric pain + weight loss, heartburn from GERD, peptic ulceration, acid hypersecretion with diarrhea, maldigestion of food (acid interferes with pancreatic E activities)
Lab: ↑BAO/MAO, ↑ serum gastrin
Dx: ulcer in distal duodenum or other atypical location, multiple ulcers, refractory to therapy, recurrence of ulcers after acid-reducing surgery
1° stomach adenocarcinoma: types? association with H.pylori?
2 types:
1)intestinal type of gastric adenocarcinoma (MC, due to H.pylori: most important; nitrosamines, smoked foods in Japan)
lesser curvature pylorus /antrum MC sites
2） diffuse type of gastric adenocarcinoma: NOT associated with H.pylori; “linitis plastica” 皮革胃，
signet ring cells infiltrate the stomach wall ➞ Krukenberg tumor of ovaries
metastasis to left supraclavicular (Virchow) node; acanthosis nigricans (黑色棘皮症）; seborrheic keratoses (脂溢性角化症; Leser-Trelat sign)
signet ring cells
diffuse type of gastric adenocarcinoma: mucin produced by the cancer cells pushes the nucleus to the periphery
spreads to both ovaries hematogenously
MCC for extranodal malignant lymphoma?
stomach: low-grade B-cell lymphoma, related to H.pylori
types of diarrhea? differentiate?
invasive (pathogens invade enterocytes); secretory loss of isotonic fluid - laxative), osmotic (hypotonic: lactase deficiency: disaccharidase deficiency in brush border)
to diff: 1) fecal smear for leukocytes (+ for invasive)
2) stool osmotic gap: normal = 300 mOsm/kg
< 50 mOsm/kg from normal: isotonic loss: secretory
> 100 mOsm/kg from normal: hypotonic - osmotic
MCC for pancreatic insufficiency
in adults: alcohol
in children: CF
malabsorption of fat + proteins, but NOT carbohydrates （amylase in salivary glands, disaccharidases in brush border epi cells in intestine)
pancreatic lipase: hydrolyzed TG to MGs (monoglycerides) + FAs
tests to differentiate sites of malabsorption
D-Xylose [zailouse] screening test: ↓ indicates small bowel disease (does NOT involve pancreatic E for absorption)
serum immunoreactive trypsin: specific for pancrease
↓ in chronic pancreatitis (note: ↑ in early CF)
Celiac disease
autoimmune to gluten in wheat
greatest association with dematitis herpetiforms (疱疹样皮炎）
Patho: multiorgan autoimmune disease; T-cell and IgA-mediated response against gluten in genetically predisposed people
tTG (tissue transglutaminase) plays pivotal role ⟹ atrophy/flattened intestinal villi, lengthening of crypts, inflammation infiltration
Dx: ↑ anti-tTG IgA, EMA-IgA (antiendomysial IgA， antigliadin IgA, IgG
clinics: steatorrhea, weight loss, fail to thrive (in children)
Whipple disease
caused by Tropheryma Whipplei
Whipple病是一种罕见的传染性疾病，Tropheryma whipplei是一种革兰氏染色阴性的细菌，也是基因组最小的细菌。它所引起的Whipple病主要症状包括体重减轻、腹泻、关节疼痛等。此外，Whipple病无孔不入，心、肺、神经系统均有累及。归类在malabsorption中。
Dr. Whipple因为发现肝脏在恶性贫血中的作用而获得1934年的诺贝尔生理学奖。
microscope: blunting of villi, foamy macrophages in lamina propria (特征性形态，和Neiman picks鉴别）
Clinic: steatorrhea, fever, polyarthritis, generalized lymphadenopathy, ↑ skin pigmentation
Rx: antibiotics
direct hernia： location?
triangle of Hesselbach (黑塞尔三角）
area of the anterior abdominal wall bounded by the inferior epigastric vessels （腹壁下AV), inguinal ligament （腹股沟韧带）and the lateral border of the rectus abdominis （腹直肌）. Direct inguinal hernias leave the abdomen through this triangle.
area blood supplied by SMA (superior mesenteric artery)? IMA (inferior mesenteric A)?
SMA: most of small bowel + ascending and transverse colon up to the splenic flexture
IMA: descending and sigmoid colons + proximal rectum + upper half of the anal canal
SMA and IMA junction: watershed area (splenic flexture)
causes for acute ischemia of small bowel?
- Acute mesenteric ischemia:1) embolism from left side of heart to the SMA (AF: MC predisposing arrhythmia); 2) thrombosis of the SMA
- nonocclusive ischemia:
1) hypotension (2° to HF)
2) hypovolemic shock
3) taking digitalis - mesenteric vein thrombosis
SB (small bowel) infarction: clinic? radiographic?
sudden onset of diffuse abdominal pain (全腹痛）， bloody diarrhea, absent bowel sounds, distention, NO rebound tenderness （反跳痛，腹膜炎体征）early in infarction
on CT: 1） “thumbprint sign” -edema in bowel wall
2) bowel distention with air-fluid levels similar to bowel obstruction
ischemic colitis: location? clinic?
splenic flexture pain (SMA ends and LMA begins: watershed of blood supply)-mesenteric angina after eating ➞ fear of eating and weight loss; bloody diarrhea
Barium study shows thumbprinting of the colonic mucosa
angiodysplasia: location? clinics?
dilation of cecal (盲肠的；cecum) submucosal venules; hematochezia (便血）， 2nd MMC hematochezia (1st MCC is sigmoid colon diverticula)
more likely to bleed if genetic/required vWD present
Meckel diverticulum:
vitelline （卵黄的) (omphalomesenteric 脐肠系膜的) duct remnant
Most common congenital anomaly of the GI tract
5 2’s: 2 inches long, 2 feet from ileocecal (回盲肠）valve, 2% of the population, Presents in first 2 years of life, Can have 2 types of epithelium (gastric and pancreatic - maybe even endometrial)
BUZZWORDS: Contains Ectopic Gastric, Pancreatic or Endometrial Tissue
Kid with massive anal bleeding with no obvious upper GI, colon or hemorrhoid cause; NB with fecal material in umbilical area
clinically can’t distinguish from acute appendicitis
Dx: 99mTc (technecium, 鍀）nuclear scan identifies parietal cells in ectopic gastric mucosa
Sigmoid colon diverticular disease
herniation mucosa/submucosa thru muscularis (sigmoid colon is the most common site for diverticula in the entire GI): mesenteric border; area of weakness where vasa recta penetrate.
MCC; constipation
MC complication: diverticulitis
clinic: fever, initial diarrhea ➞ constipation, left lower quadrant pain (“left-sided appendicitis”)
best Dx: CT-scan
MC for hematochezia and fistulas
IBS (irritable bowel syn)
intrinsic colonic motility disorder, responsible for > 50% referral to gastroenterologists
alternating constipation/diarrhea; ↑ mucus in stool
Rx: adequate fiber intake
carcinoid tumor
MC SB tumor, malignant neuroendocrine tumors
depending on the location and size, they either invade or metastasize
MC location: vermiform （蠕虫样）appendix （bright yellow)-rarely metastasize
If in terminal ileum: metastasis to liver➞ cause carcinoid syn.
症状全是由liver代谢serotonin产生的5’-HIAA引起：
5’-HIAA is excreted in the urine ➞ for Dx
clinic: 1) flushing (serotonin ➞ vasodilation in skin)
2) diarrhea (serotonin ➞ bowel motility ↑)
3) wheezing, dyspnea (serotonin ➞ bronchospasm)
4) tricuspid regurgitation, pulmonary stenosis (serotonin ➞ collagen production in the valves)
5) facial telangiectasia
Dx: ↑ urine 5’-HIAA, CT scan of liver, Scanning for 1° location and metastasis
acute appendicitis
patho:
1) children: lymphoid hyperplasia 2° of a viral infection
2) in adults: fecalith obstruction (similar to acute diverticulitis)
pathogens: E coli, Bacteroides fragilis
特征性疼痛（转移）：initially colicky periumbilical pain (afferent C fibers on viseral pertitoneal surface: refer pain to midline) ➞ then shifts to RLQ in 12-18 hrs (Aδ fibers localize pain)
pain PRECEDES nausea and vomiting (important to Dx children！！）
MC complication: periappendiceal abscess
pyelophlebitis (肾盂静脉炎）：infection of the portal vein, danger of portal vein thrombosis
-subphernic abscess: persistent postoperative fever
Dx: spiral CT
congenital pyloric stenosis (CPS)
may associated with genetic factors (if parents affected, ↑ risk for child); male > famale baby
patho: caused by progressive hypertrophy of the muscles in the pyloric sphincter (↓ NO synthase)
NOT present at birth: occurs at 3-5 wks
projectile vomiting of non-bile-stained fluid; hypertrophied pylorus can be palpated in the epigastrium, “olive-sized” mass if felt in the right upper abdomen
chronic mesenteric ischemia: cause? characteristics? Dx?
atherosclerosis, ↓ blood flow (patho similar to angina pectoris)
特征性症状：
1） epigastric (上腹部）or periumbilical pain, 30-60 min after meals: very severe pain, patients fear to eat, but no findings on physical exams
2) weight loss
Abetalipoproteinemia: cause? clinics? microscope?
microscope: normal intestinal mucosal architecture, but the enterocytes contain clear or foamy cytoplasma prominent at the villi tips: accumulation of lipids (此病特征）；
cause: impaired formation of ApoB-containing lipoproteins
AR, loss-of-funciton of MTP gene (microsomal triglyceride transfer protein， chaperon for ApoB folding and tranfer lipids to chylomicrons and VLDL). Lipids absorbed by the SB can’t be transported to blood, so accumulate in the intestinal epithelium ⟹ enterocytes with clear or foamy cytoplasm
lab: very low serum TG and cholesterol; absent chylomicrons, VLDLs, apoB
clinic: < 1yr发病，malabsorption （abdominal distention, foul-smelling greasy stool); ↓ fat-soluble vit ⟹ acanthocytes, neurological abnormalities
adenoma-to-carcinoma sequence
adenomatous polyps: premaligant
> 50 yr patients, mutation of APC gene
stepwise progression with gene mutation: PAC inactivation ⟹ COX2 overexpression ⟹ K-ras acivation, DCC, p53 inactivation
↑ COX2 activity in some colon adenocarcinoma, and in inherited polyposes syn; Aspirin (COX inhibitor) can ↓ adenomas
Mallory-Weiss syn
longitudinal mucosal tear in esophagus-gastric junction
due to severe retching, often associated with alcoholism or bulimia (暴食）. tear occur 2° to rapid ↑ of intraabdominal /intraluminal gastric pressure
hematemesis
differentiate ulcerative colitis vs Crohn’s diease
both can have bloody diarrhea (both are inflammatory bowel disease). They are inherited as a complex, multigenic disorder (non-Mendelian manner). Candidate genes: HLA association (HLA-DR1/DQW5 in Crohn’s, HLA-DR2 in ulcerative colitis) and NOD2 (triggers NF-kB pathway ⟹ cytokines)
ulcerative colitis:
1) rectum always involved
2) inflammation: limited to mucosa and submocosa ONLY
3) mucosal damage is continous
4) . bloody diarrhea, with or without pain, is HALLMARK
collection of neutrophils within crypt lumina
Crohn’s disease:
transmural inflammation, perianal fistulae, non-caseating granuloma
serological findings for HAV: IgM? IgG?
anti-HAV IgM: infeciton
anti-HAV IgG: recovery/vaccination
Reye Syn
associated with Aspirin+ infection (chickenpox, influenza, etc): reason not to give Aspirin to children!!! fatal, damage liver and brain; usually in children < 4 yr
Postinfectious triad: encephalopathy, microvesicular fatty change of liver, ↑ transaminases, bilirubin, PT, ammonia, ↓ glucose (hypoglycemia)
cause for hepatic artery infarction?
liver transplantation
PAN (polyarteritis nodosa)
portal vein thrombosis: cause? clinic?
cause: 1) pylephlebitis (门静脉炎）： MC due to acute appendicits, air in the portal v from bacterial gas;
2) polycythemia vera 真性红细胞增多: hyperviscosity of blood
3) hepatocellular carcinoma
clinic: ascites, PH, air in PV, splenomegaly, NO HEPATOMEGALY!!
Budd-Chiari syn
Hepatic vein thrombosis
MCC: 1)polycythemia vera
2) hypercoagulable state; 3) hepatocellular carcinoma
painful hepatomegaly, splenomegaly, fever, PH, ascites
Dx: Pulse Doppler Ultrasound, MRI
Alcoholic hepatitis病理？
acetaldehyde damages hepatocytes
fatty change, neutrophil infiltration, mallory bodies (ubiquntinaited cytokeratin intermediate filaments in inclusions in hepatocytes)
Dx for acute cholecystitis?
Nuclear medicine hepatobilitary scans (HIDA scan): fail to visualize gallbladder
If Dx with US: distended gallbladder, thickened wall, pericholecystic fluid, positive sonographic Murphy sign
mechanism for E2 to affect gallstone?
E2 ↑ hepatic HMG-CoA reductase: this enzyme ↑ synthesis of cholesterol ⟹ cholesteral gallstone formation
effect of 7α-hydroxylase on gallstone formation?
7α-hydroxylase converts cholesterol into bile acids ⟹ ↓ cholesterol within the bile
suppress this enzyme by fibrate medications ↑ concentrations of cholesterol in the bile
function of β-glucuronidase in gallstone formation
β-glucuronidase de-conjugates bilirubin. The resulting free bilirubin complexes with calcium ⟹ precipitates in the bile
↓ activity of β-glucuronidase ⟹ ↓ pigmented gallstones
types of gallstone?
- cholesterol gallstones: yellow, radiolucent
- pigmented gallstones:
1) black: sign of chronic extravascular hemolytic anemia (sickle cell anemia, hereditary spherocytosis)
2) brown gallstones: (Asians, infection in CBD): infection de-conjugates CB, ⟹ ↑UCB in bile, cause the brown pigment stones
MC benign tumor of liver?
cavernous hemangioma 海绵状血管瘤
先天性，和hyperplasia, hypertention无关。不能活检，引起大出血
which liver tumor can regress with the discontinuation of OCP (oral contraceptives)?
hepatic ademonas (note: 与cavernous hemangioma区分！后者不受避孕药影响）
PBC (primary biliary cirrhosis)
autoimmune destruction (CD8+ T cell) of bile ducts in triads female dominant, associated with other autoimmune disease (ie, Sjogren Syn)
↑ anti-mitochondrial Ab (AMA), ANA, IgM
precirrhotic stage: interlobular bile ducts are destroyed by granulomatous inflammation; heavy portal tract infiltrate of macrophages, lymphocytes, plasma cells, and eosinophis - similar to GVHD
late stage: necrosis, generalized cholestasis; gross: liver stains green + uniformly micronodular
Cx: early pruritus, late jaundice
Budd-Chiari syn
Hepatic vein thrombosis
MCC: polycythemia vera
hypercoagulable state: ie OCP, protein C and S deficiency, hepatocellular carcinoma
Cx: enlarged, painful liver; PH, ascites, splenomegaly
BUZZWORDS: Seen with Hepatic (Posthepatic) Venous Thrombus that occludes Hepatic Vein or IVC
Wilson disease
AR, mutation in ATP7B gene in chr#13: copper metabolism disorder: ↓incorporation copper into ceruloplasmin (血浆铜蓝蛋白， protein synthesized in the liver, contains copper) , ↓ excretion copper into bile ⟹ precipitate in cornea (Kayser-Fleischer ring， detected by slit lamp) and basal ganglia (PD-like syn)
young patients (3 -40), liver and brain damaged
acute, fulminate, chronic hepatitis, PH, cirrhosis;
PD-like tremor, slurry speech, depression,
hemolytic anemia, renal disease (damage proximal tubule ⟹ Fonconi syn)
Dx: liver biopsy finding quatitative liver copper > 250 mcg/g, ↓ serum ceruloplasmin
Rx: Penicillamine (Cu chelator)
Acute hepatitis B 症状？
“serum sickness-like” (malaise， fever, skin rash, pruritis, joint pain) first; after these sym are gone, surge of ALT and AST (ALT > AST), ⟹ then ↑ bilirubin, Alkaline phosphatase
hereditary hemochromatosis
AR, male dominant
missense mutations in HFE gene on chr 6, ⟹ mutation in sensor for circulaiting iron in basallateral epi in intestine ⟹ unrestricted iron reabsorption by duodenum ⟹ iron stimulates production of hydroxyl free radicals ⟹ liver damage
“bronze diabetes” (skin hyperpigmentation + DM + cirrhosis with hepatomegaly) , malabsorption, restricted cardiomyopathy, degenerative arthritis
↑ serum iron, % saturation, ferrintin, ↓ TIBC (total iron binding capacity)
Rx: % saturation is the best screen
serum ferritin used to follow Rx
gene testing best for screening relatives
liver cirrhosis and hepatocellular carcinoma are the 2 most ominous potentail complications
women tend to present later due to the blood loss during menstruation and pregnancy
How does HBV cause hepatocyte damage?
HBV itself has NO cytotoxic effect itself. The presence of viral HBsAg and HBcAg on cell surface, with MHC-I, stimulates the host’s cytotoxic CD8+ T cells to destroy infected hepatocytes.
stages of alcohol-associated hepatic injury? Px?
3 stages: steatosis (reversible), alcoholic hepatitis (resersible), cirrosis (irreversible)
hepatocyte damage (ALT, AST, etc） ⟹ loss of hepatic function (↑ PT, ↓hypoalbuminesia: indicator of liver failure and poor Px)
acute acalculous cholecystitis
无结石胆囊炎
common in hospitalized patients; arise secondary (after sepsis, immunosuppression, major trauma, burns, infection, etc) to gallbladder stasis and ischemia
与胆结石引起的胆囊炎区别：无结石胆囊炎有jaundice and palpable right upper quandrant mass (胆囊突出肋骨缘）
结石胆囊炎：Murphy sign
porcelain gallbladder indicate?
a rim of calcium deposits outline the gallbladder; associated with gallbladder carcinoma;
markers for?
AFP CEA (carcinoembryonic antigen) CA-125 prostate-specific Ag acid phosphatase human chorionic gonadotrophin
AFP - hepatocellular carcinoma
CEA (carcinoembryonic antigen) - colon cancer
CA-125: ovarian cancer
prostate-specific Ag: screen for prostate cancer
acid phosphatase: 2° prostate cancer Ag, also in active osteoclast-initiated bone resorption
human chorionic gonadotrophin: gestational trophoblastic disase
viral hepatitis on liver biopsy?
panlobular lymphocytic infiltrations, ballooning hepatocytes, necrosis, apoptosis
Apoptotic hepatocytes form round acidophilic bodies (Councilman bodies, or apoptotic bodies)
pathogenesis of alcohol-induced hepatic steatosis
alcohol DH (dehydrogenase), aldehyde DH ⟹ ↑ NADH production ⟹ ↓ FA oxidation ⟹ accumulation of TG in hepatocellular cytoplasm
black gallstone is associated with?
intravascular hemolysis (sickle cell anemia, β-Thalassemia, hereditary spherocytosis) - when circulating unconjugated bilirubin ↑; often seen in rural Asian populations
gallstone types: cholesterol, black, brown (infection)
patho for brown gallstone
infection damages hepatocytes ⟹ release of β-glucoronidase, ⟹ hydrolysis of bilirubin glucuroninides ⟹ ↑ unconjugated bilirubin in bile
azotemia: types? cauases?
azotemia: ↑ serun BUN + creatinine (Cr)
urea: filtered; partly reabsorbed in proximal tubules
creatinine: filtered
serum BUN/Cr ratio: normal = 15
1) prerenal azotemia: ↓ CO (hypoperfusion of kidney), ↓ GFR, ↑ BUN: ratio > 15
2) renal azotemia: intrinsic renal disease, extra loss of urea: ratio ≤ 15
3) postrenal azotemia: obstruction past kidneys (stone, cancer, etc); initially ratio > 15; ≤ 15 if obstruction persists to damage parenchymal
Linear immunofluoresence in kindey: indicate what disease?
Granular IF?
fusion of podocytes?
linear IF: anti-GBM disease (e.g: Goodpasture Syn)
granular IF: immunocomplex deposition in the glomerulus (if do this under EM: dense deposits: the normal BM has a light grey apprearance)
fusion of podocytes: nephrotic syn
Nephritic syn vs. nephrotic syn
Nephr(i)tic syn (肾病综合症）：neutroph(i)l-related injury to glomerul(i)
Cx: HT due to salt retention; periorbital puffiness/pitting edema, ↑ plasma hyrdostatic pressure, oliguria (~ 400 mL/day, due to ↓ GFR in inflamed glomeruli), moderate proteinuria (150 mg ~ 3.5 g/24 hr), hematuria, dysmorphic RBC, neutrophils are present in the urine sediment. Tubular function is intact!
Key to Rx: RBC casts
Nephr(o)tic Syn: cyt(o)kine injury p(o)docytes; negative charge on GBM is lost, etc ⟹ ↑ permeability of glomerular cap, MASSIVE protein loss (特征）, ↑ liver synthesis of albumin can’t compensate ⟹ ↓ colloid osmotic pressure ⟹edema ⟹ decreased intravascular volume ↓ renal perfusion pressure ⟹ 1) activation of renin-AngII- aldoesterone, 2) secrete antidiuretic hormone, both cause water and sodium retention
Key Rx: proteinuria > 3.5 g/24 hr, fatty casts (特征：蛋白尿和脂肪尿显著）
Generalized pitting edema and ascites due to hypoalbuminemia ⟹ ↓ plasma oncotic pressure
hypercoagulable (lose antithrombin III), hypercholesterolemia, hypogammaglobulinemia
Diabetic glomerulopathy
MCC for CRF in US, type I DM > type II
non-enzymatic glycosylation of the GBM and tubular BM: ↑ permeability to protein
hyaline arteriolosclerosis, involve efferent arterioles before afferent arterioles;
glucose is converted by aldose reductase to sorbitol ⟹ ↑ osmotic damage
microangiopathy: ↑ deposition of type IV collagen
1st lab sign: microalbuminuria (Rx: ACE inhibitor)
patho of BNS (benign nephrosclerosis)
hyaline arterioslcerosis
kidney of essential HT
Malignant HT: preexisting BNS MCC
hyperplasic arteriolosclerosis (onion skin lesion); > 210/120 mmHg, encephalopathy, RF
Rx: IV nitroprusside
renal cell carcinoma: MCC?
smoking MCC
Von Hippel-Lindau disease： AD, chr3; translocation with loss of VHL suppressor gene (if see upper pole mass with cysts and hemorrhage: reminder of VHL)
bright yellow tumor with renal vein invasion; cancer derives from proximal tubular cells
microscope: clear cells contain lipid
invade renal vein, inferior vena cava （extend to right heart) ⟹ poor Px
metasize to lung, bone, regional nodes
RCC triad: hemauria, flank pain, abdominal mass
ectopic secretion of EPO (⟹ 2° polycythemia) and PTH-related peptide (hypercalcemia)
mechanism of Enalapril on GFR?
- Enalapril (依那普利）：ACE inhibitor: inhibit Ang II
- Ang II: 1) systemic vasocontriction; 2) preferentially constrict efferent arteriole; 3) ↑ adrenal cortical aldosterone secretion
Enalapril acutely ↓ systemic vascular and efferent arteriolar resistance, both ⟹ ↓ GFR
tumor lysis syn: happen in which segment of kidney?
distal tubules and collecting ducts
in chemo for lymphomas, leukemia, etc （rapid cell turnover and high sensitivity to chem）： rapid destruction of cells during chemo ⟹ release intracellular ions and uric acids are released into blood
the lowest pH along the nephron is in distal tubules and collecting ducts ⟹ uric acid precipitation
risk of tumor lysis syn can be ↓ by urine alkalinization and hydration
IgA nephropathy can be caused?
1) HSP (Henoch-Schonlein purpura) 2) Berger disease
both: mesangial proliferation and crescent formation, 看肾脏无法区分
HSP: triad (abdominal pain + joint pain + palpable purpura on buttocks and lower extremities); hemauria
Berger disease: children + young adults; painless hematuria 2-3 days after upper RT infection; hematuria lasts for several days and subsides, but return every few months.
RBC casts: Dx?
fatty casts?
RBC casts: nephritic syn (IHC: “starry sky”)
fatty casts: nephrotic syn
PSGN (poststrepococcal glomerulonephritis
BUZZWORDS: Kids after Pharyngeal or Skin Infection (Mosquito Bite);
usually group A beta-hemolytic streptococci (impetigo, 脓疱病）
Immune Complex Mediated; - nephritic syn一种（RBC cast)
Cx: periorbital edema, cola-colored urine, oligouria, HT; ↑ anti-streptococcal Ab, ↓ serum C3
IHC: “starry sky”: granular deposits of IgG, IgM, C3 in GBM and mesangium
EM: subepithelial humps (electron-dense deposit of Ag-Ab complexes at the epithelial surface)
光镜：hypercellular glomerulus
Important factor for Px: age (if in adults: poor Px, 40% will become chronic GN)
linear deposits of Ig： Dx?
anti-GBM = Goodpasture Syn
deposit: IgG (anti-Type IV col), C3 [important: GBM is composed of type IV collagen]
Differential: IgM and C3 deposits are found in focal segmental glomerulosclerosis, but no linear deposit of Ig
特征Dx for Goodpasture Syn?
crescents in the glomeruli on light microscopy +
under fluorescence: see linear deposits
Cx: pulmonary (hemoptysis) + kidney (hematuria)
属于type I RPGN (rapid progressive glomerulonephritis),
Dx: crescent formation under light microscopy?
RPGN (rapid proliferative/crescentic glomerulonephritis)
fibrin deposits是crescent formation关键一步
types and characteristics of RPGN (rapid progressive GN)?
All have crescent formation, fibrin deposition
Type I: anti-GBM Ab (Goodpasture); linear IgG and C3
Type II: immune complex-mediated: “lumpy bumpy” granular pattern; (SLE, HSP, IgA nephropathy/Berger’s, PSGN)
Type III: pauci-immune (no Ig or complement deposits on BM): anti-ANCA (anti-neutrophil cytoplasmic Ab) [Wegener’s or idiopathic]
Dx: circulating IgG4 Ab to the PLA2R (phospholipase A2 receptor)?
idiopathic membranous nephropathy
Dx: ARF sym (oligouria) + ballooning, vacuolar (空泡样）degeneration of proximal renal tubules + oxalate crystals in tubular lumen
ethylene glycol (乙二醇）中毒
earliest detection for diabetic nephropathy?
patho change?
albumin (microalbuminuria)
光镜特征：nodular glomerulosclerosis (Kimmelstiel-Wilson disease): round/oval shape, laminated and eosinophilic on HE stain, PAS+
Dx: elder man, gross hematuria, history of smoking or occupational exposure to rubber, plastics, dyes, textiles, or leather?
transitional cell carcinoma of the bladder
Which cells in the kidney will go hypertrophy and hyperplasia in kidney hypoperfusion?
SMCs in JG (juxtaglomerular) apparatus of the afferent or efferent arterioles
hypoperfusion ⟹ JG SMCs secrete renin ⟹ convert Ang I to Ang II ⟹ ↑ aldosterone release and vasocontriction ⟹ retension of sodium and water
Why is anti-CD3 Ab used in treating acute rejection in kidney, liver, heart transplatation?
acute rejection: mediated by CD4+ Th mononuclear cells (MHC class II receptor +/IL-2 receptor +)
CD3 is required for proper function of CD4+ Th cells
Cx for Wegener’s disease?
polyangiitis + granulomatosis
累及upper respiratory tract (sinusitis, nasal ulcer),
pulmonary (hemoptysis) , kidney (RPGN: oligouria)
Diff with Goodpasture (累及肺和肾脏）: Wegener’s associated with c-ANCA (anti-neutrophil cytoplasmic Ab)
major pathophysiologic abnormality caused by pain killers (NSAID, Cox-2 inhibitor, etc)?
chronic interstitial nephritis
kids with recent upper RI infection ⟹ nephronpathy
如何鉴别是PSGN vs. Berger disease?
timing of the renal syn/ C3 level helps to differentiate:
PSGN: a few weeks to develop renal syn / ↓ C3 level
Berger： a few days / normal C3
Berger’s Dx is made by the detection of IgA deposits in the mesangium of glomeruli on IFM
Dx: cystic dilatations of the medullary collecting ducts?
medullary sponge kidney (MSK)
MC complication: kidney stone
Dx: renal biopsy shows eosinophilic casts?
multiple myeloma - Bence Jones protein (light chain)
why use mesna when giving cyclophosphamide?
cyclophosphamide: chemotherapy for cancer or autoimmune diseases
美司钠在临床上用于降低环磷酰胺和异环磷酰胺化疗引起病人出现血尿及出血性膀胱炎的可能性。环磷酰胺和异环磷酰胺在膀胱中会被转化成丙烯醛，而后者具有对膀胱上皮细胞的高度性，能够引起出血性膀胱炎，甚至膀胱癌。[1][2] 美司钠的巯基部分能够与丙烯醛的碳碳双键反应，生成无毒无反应活性的硫醚复合物并排泄出人体，从而在不影响疗效的情况下起到了泌尿系统保护剂的作用。[3][4] 同时它还有抗氧化剂的作用，而这进一步保护了泌尿系统，使其免受化疗药物代谢产物的伤害
zones of prostate? BPH happens where?
peripheral (MC site for prostate cancer) transitional zone (MC for the glandular component of BPH) periurethral zone (MC for the fibromuscular/stromal component of BPH)
patho: ↑ sensitivity to DHT
stromal cells contain 5a-reductase; are the site of DHT synthesis
BPH is NOT a risk factor for prostate cancer!
obstructive uropathy is an early sign for BPH, but not for prostate cancer （发现常是晚期，locate in peripheral zone)
prostate cancer“ patho? Cx? metastasis? Lab?
patho: DHT-dependent
generally silent until advanced; obstructive uropathy indicates extension into the bladder base;
放射痛：lower back, pelvic, inguinal
metastases：血行转移最常见为骨转移： lumbar spine, pelvic bones (via Batson vertebral venous plexus) ⟹ compression of the spine cord
Lab: ↑ serum ALP, ↑ PSA (prostate specific Ag, sensitive but not specific for cancer - could be ↑ in BPH: if > 10 ng/mL: highly indicate cancer);
Diff between BPH: ↑ free PSA: consider BPH
↑ bound PSA: consider cancer
Dx: transrectal needle core biopsy, imaging (radionuclide bone scan
function in male: FSH? LH? T? SHBG (sex hormone-bindng protein)?
FSH: + spermatogenesis, negative feedback with inhibin (synthesized by Sertoli cells 睾丸支持细胞）
LH: + T synthesis in the Leydig cells in the testes; T negative feedback to LH
SHBG: bind to both T and E2;
major synthesis site: liver; in male T also + synthesis in Sertoli cells; E2 ↑ liver synthesis
↑ SHBG causes ↓ free T; ↓ SHBG causes ↑ free T
primary hypogonadism: types? Cx?
1) due to Leydig cell dysfunction (Leydig cell: 睾丸里生成T的细胞）： ↓ T, sperm count; ↑ LH (没有了T的negative feedback; normal FSH - Sertoli cells not affected) = hypergonadotropic hypogonadism
2) due to Leydig cell dysfunction + seminiferous tubule (细精管）dysfunction: 和1）一致： ↓ T, sperm count, ↑ LH; 不一致：↑ FSH (loss of inhibin feedback to FSH)
Kallmann Syn?
AD, maldevelopment of olfactory bulb and GnRH-producing cells in the anterior pituitary (GnRH stimulates FSH and LH) ⇒ ↓ GnRH, FSH, LH, T, sperm count, delayed puberty + anosmia (嗅觉缺失）
MCC impotence in men > 50 yr?
vascular insufficiency
Leriche syn: aortoiliac atherosclerosis ⟹ ↓ penal blood flow, calf claudication and atrophy, ↓ femoral artery pulse
控制erection vs ejaculation的神经节段？
Parasympathetic for erection: S2 - S4
sympathetic for ejaculation: T12 - L1
mechanism for Sildenafil?
Viagra: inhibit the breakdown of cGMP by type 5 phosphodiesterase ⟹ ↑ cGMP, cause vasodilation in corpus cavernosum (海绵体）
pap smear: location? findings?
have to sample TZ (transformation zone for the potential SCC): presence of metaplastic squamous cells or mucus-secreting columnar cells indicating proper sampling; absence of these cells means the Pap smear must be repeated
Superficial cells: indicate adequate E2 intermediate cells: indicate adequate P4 parabasal cells (atrophoic): lack of E2 or P4
normal nonpregnant adult: 70% superficial + 30% intermediate
normal pregnant: 100% intermediate
elderly: 100% parabasal, inflammatory cells
patho characteristics for HPV?
associated with CIN (cervical intraepithelial neoplasia) - precursor for SCC
HPV type-6, 11: low risk
HPV type-16, 18: high risk
病理特征：koilocytosis in squamaous cells (clear halo/pyknotic nucleus)
CIN classification
cervical intraepithelial neoplasia/dysplasia
CIN I: mild, lower 1/3 of the epithelium (can reverse to normal)
CIN II: moderate, lower 2/3 of the epithelium
CIN III: severe, involve the full thickness
10 yrs for CIN I to CInN III
10 yrs for CIN III to cervical cancer
Krukenberg tumor
signet ring cells, implicate diffuse cancer of the stomach or breast as the primary site
bilateral; multinodular outer appearance
Lab findings in Klinefelter Syn?
47 XXY; MCC for gynecomastia (男子女性型乳房）
histology: some or all of the testicular tubules atrophied/ replaced by pink, hyalinized tissues
Lab: ↑ FSH, E2, ↓ T; E2: T ratio determines the extenf of feminization
function:
aromatase?
21- or 17-hydroxylase?
5a-reductase?
HMG CoA reductase?
aromatase: T → E2 in ovaries, testes, placenta and other peripheral tissues; and androstenenone → estrone
21-hydroxylase: a cytochrome P450 enzyme that is involved with the biosynthesis of the steroid hormones aldosterone and cortisol
deficiency: MC type of congenital hyperplasia (CAH); Cx: ambiguous genitalia in the female fetus, salt wasting, hypotension, hyponatremia, hyperkalemia
17-hydroxylase: rare form of CAH: sodium retention, HT (和21-hydroxylase缺乏相反）， sexual infantilism in females
5a-reductase:
fever, maculopapular rash + acute renal failure 1-3 wks after treatment with β-lactam antibiotics (ampicillin)， NSAIDs, diuretics: Dx?
AIN (acute interstitial nephritis)
important Dx clue: peripheral eosinophilia and eosinophiluria (drug-induced hypersensitivity reactions are the cause)
Symptoms resolve completely after cessation of the medication
Parinaud syndrome
tumors in pineal gland: pinealoma
Paralysis of Conjugate Vertical Gaze
Brain Lesion in Superior Colliculus/Pretectal Area
Presentation:
Paralysis of Upward Gaze (setting-sun sign)
Bilateral Papilledema if causing noncommunicating Hydrocephalus by blocking Cerebral Aqueduct
Accommodation, but lack of Pupillary Light Reflex
the pineal region is the most common location of brain germinomas. Histologically very similar to testicular seminomas. Clinically: precocious puberty,
MCC of hypopituitarism in children?
craniopharyngioma (颅咽管瘤）
benign tumor derived from Rathke pouch remnants; Rathke pouch is derived from the oral ectoderm, and develops into the anterior lobe of the pituitary gland;
tumor extends into the sella turcica (蝶鞍）and destroys the gland; compress optic chiasm ⇒ bitemporal hemianopia (偏盲）；
may cause CDI (central diabetes insipidus, 尿崩症）
DiGeorge Syn
3rd/4th pharyngeal pouches undevelpped:
3rd: superior parathyroid
4th: inferior parathyroid + thymus
Cx: hypoparathyroidism + no thymus shadow
Waterhouse-Friderichsen syn (WFS)
N. meningitidis sepsis ⇒ endotoxic shock, release of tissue thromboplastin, damage the endothelial cells ⇒ DIC ⇒ bilateral adrenal hemorrhage (infarction)
cause acute adrenocortical hypofunction
Addison disease
“A” - chronic “a”drenal insufficiency
- “a”utoimmune destruction: MCC in US
- military TB: MCC of addison disease in developing countries
- MCC in children: adrenogenital syn
Cx: weakness and hypotension (Na+ loss from mineralocorticoid and glucocorticoid deficiency), diffuse hyperpigmentation (↑ plasma ACTH stimulates melanocytes)
Lab: ↓ Na+, cortisol, bicarbonate; ↑ K+, ACTH (醛固酮促进肾脏Na-K交换；缺乏醛固酮引起metabolic acidosis）；hypoglycemia (↓ cortisol, which is gluconeogenic), eosinophilia, lymphocytosis, neutropenia (due to ↓ cortisol)
MCC for adrenogenital syn?
classic 21-hydroxylase deficiency: (P4 converted to mineralocorticoid/cortisol)
impaired mineralocorticoid/cortisol production: salt loser, ↑ androgens
MEN type I
MEN like 3P:
Parathyroidism (hyper)
Peptic ulcer due to gastrin-secreting tumor in pancrease;
Pituitary adenoma
diff. Cushing syn
- pituitary Cushing: ↑ ACTH, ↑ cortisol (can be suppressed by high-dose dexamethasone, DXM)
- adrenal Cushing: ↓ ACTH, ↑ cortisol
- ectopic Cushing: ↑↑ ACTH, ↑ cortisol (MCC: small cell carcinoma of lung; thymus, thyroid)
Cx: truncal obesity (↑insulin), thin extremeties (↑ cortisol, muscles breakdown), purple stria
weight gain: due to hyperinsulinism from hyperglycemia: insulin ↑ fat deposit in adipose and retain Na+
Does hypernatremia happen in mineralocorticoid excess?
No - although Aldoesterone ↑ Na+ /H2O retention, excrete K+ and H+, increased Na+/H2O also ↑ renal BF and GFR ⟹ ↑ Na+ excretion; ↑ intravascular volume also ↑ release of ANP ⟹ natriuresis, so 虽然醛固酮保钠排钾，却很少在病人中见到高钠血症
Cx for aldosterone ↑： HT, hypokalemia, matabolic alkalosis, without marked hypernatremia
Cx: MEN 1, MEN 2A, MEN 2B?
MEN 1: 3P (AD, tumors of the parathyroid gland, pituitary, pancreas)
MEN 2A: medullary carcinoma of the thyroid, pheochromocytoma, oral/intestinal mucosal neuromas, parathyroid hyperplasia TPPGI (踢PP的胃肠道）
MEN 2B: Cx for 2A WITHOUT parathuyroid hyperplasia
Cause of amenorrhea in anorexia nervosa?
Loss of pulsative secretion of GnRH from the hypothalamus (not the pituitary or ovary!)
Low E2 for long-term can cause osteoporosis
Paget’s disease of the bone
Osteitis Deformans
Increased Osteoblast and Osteoclast activity (with Osteoclast predominating) causing abnormal Bone Architecture (Inc Resorption an replaced with poorly mineralized matrix - looks woven)
BUZZWORDS: Mosaic Pattern of Bone Marrow Replacement; High-Output Cardiac Failure; Bigger Hat/shoe Size
Cause: Possibly due to Paramyxovirus
Phases:
Osteolytic Phase, Osteoblastic Phase
Presentation:
Often Polyostotic (Skull, Pelvis, Femur, Vertebrae, possibly Humerus)
Bone Pain (especially affects Spine and Calvarium)
Bone Enlargement (Skull enlargement with Frontal Bossin) - Need bigger hat size, or shoe size
Hypervascular Bone - warms overlying skin
Fracture
Arthritis
Hearing Loss due to Auditory Foramen narrowing
Diagnosis:
Normal Calcium, Phosphorus and PTH levels - BUT Very Inc Alkaline Phosphatase
Mosaic Bone Pattern (Enlarged, inc bone density with cortical thickening, Radiolucent Bones) with irregular cement line and thick bony trabeculae - seen later on
Chalk-Stick Fractures in Long Bones
Complications:
Can lead to Osteogenic Sarcoma
High-Output Heart Failure from inc blood flow from increased Arteriovenous Shunt
diffenrential between RA and OA (osteoarthritis)
RA: morning stiffness IMPROVEs with use, last > 30 min and may linger for hours; involves MCP (metacarpophalangeal) and PIP joints, not DIPs
OA: use-dependent joint pain in weight-bearing joints, impoves with rest, could have morning stiffness but < 30 min, involve DIP and PIP
bullous pemphigoid 大疱性类天疱疮 特征
elderly patients, autoimmune (Ab against hemidesmosomes along the basement membrane of the dermal-epidermal junction)
blister (>2 cm in diameter) on inner thighs, flexor asepects of the forearms, axillae (腋下），groin, lower abdomen
Diff: rubeola vs. rubella
rubeola (regular measles):
caused by RNA paramyxovirus (副粘液v), prodrome (前驱症状）3Cs (cough, coryza - 鼻炎，conjunctivitis); koplik spots appear first, then rash; confluent on face and truck, but discrete on extremitis;
complications: giant cell pneumonia, acute appendicitis in children, encephalitis
NOT TERATOGENIC
rubella (German measles) 德国鬼子比较凶残
caused by RNA togavirus (批盖病毒），3-day measles, at first: dusky red spots on palate, then maculopapular rash begins at hairline and rapidly spreads cephalocaudally: NOT confluent, 特征性painful postauricular lymphadenopathy (耳后淋巴结肿痛）
TERATOGENIC!
roseola infantum: cause? Cx?
HHV-6 (human herpesvirus 6), MC viral exanthem (皮疹）in children < 2yrs old
erythematous macules develop on soft palate 48 hrs BEFORE rash;
high fever, then 3-7 days LATER: abruptly develop maculopapular rash；
may precipitate a febrile convulsion (热性惊厥）
与rubella (German measles)鉴别的重要要点：tender cervical and/or posterior occipital (枕骨）lymphadenopathy is the key!!! (rubella: 耳骨后疼痛性淋巴结肿大）
Paralysis of upward gaze: ? syn
“locked-in” syn indicates?
Symptoms for cerebellar lesions?
Parinaud syn (Dorsal midbrain syn) - tumor in pineal region, such as germinomas (malignant germ line tumor, cause precocious puberty in boys)
locked-in syn: pontine hemorrhage or tumor
Cerebellar lesions: gait and limb ataxia (can’t walk), intention tremor, nystagmus (眼球震颤）
ataxia + dysarthria, degeneration of the posterior columns + spinocerebellar tracts: Dx?
VE deficiency or Friedreich ataxia
ischemic stroke后按时间段的病理变化？ 24-48 hr？ 3-5 days? 2 wks?
first 48 hrs: neuron death (red neurons), neutrophils migrate into the area
3-5 days: microglia, phagocytosis of lipids (from breakdown of myelin)
2 wks: gliosis: astrocytes migrate and proliferation
VDRL tests what?
syphilis
(venereal disease research lab test)
If VDRL + in CSF: neurosyphilis
MC neoplasm of childhood, and microscopic presentation?
MC #1: pilocytic astrocytoma 毛细胞性星形细胞瘤
located in cerebellum (diff vs. medulloblastoma), see pilocytic astrocytes and Rosenthal fibers; prognosis better than medulloblastoma
MC #2: medulloblastoma, part of a group called PNETs (primitive neuroectodermal tumors); in cerebellum (⟹ ataxia, gait instability); sheets of small cells with deeply basophilic nuclei and scant cytoplasm (small, round, blue cells); abundant mitosis
MC #3: ependymomas 室管膜瘤
arise in the walls of ventriculi, can hamper CSF flow to cause hydrocephalus; form gland-like “rosettes”
Dx between dementia: early presentation of gait disturbance + urinary incontinence?
NPH (normal pressure hyrdocephalus)
can progress into dementia, loss of short-term memory, emotional blunt (Diff vs. AD)
Cranial tumor， S-100 positive, biphasic (dense/loose) pattern, elongated (spindle) cells with regular, oval nuclei: Dx?
Schwannoma;
melonoma is also S-100 +: both are from neural crest
Horner’s syn
交感神经损伤； 副交感activity ↑
ipsilateral
1) partial ptosis (drooping of upper eye lid): denervation of the sympathetically controlled Muller muscle of the upper lid
2) miosis (缩瞳）：interruption of the sympathetic fibers to the dilator pupillae muscle
3) anhydrosis (impaired sweating)
causes: MC lung adenocarcinoma (compress the brachial plexus causes ipsilateral shoulder pain, hand muscle atrophy, loss of deep tendon reflexes)
can also be caused by lesions in the spinal cord and brain stem
Dx: proximal muscle weakness + pre-existing tumor + ↑ muscle response on repetitive motor nerve stimulation
Lambert-Eaton Syn, （Ab against presynaptic Ca2+ channel); diff vs. myasthenia gravis (Ab agaisnt Ach R)
Dx: brain watershed infarcts (bilateral wedge-shaped bands of necrosis over the cerebral convexity, just a few cm lateral to the interhemispheric fissure)
caused by global cerebral ischemia (= ischemic-hypoxic encephalopathy）
can be caused by extensive MI (not cardiac embolism, which leads to infarcts in different vascular territories)
Dx: skull fracture, loss consciousness quickly and regain it, feel well for hours (lucid interval) and then loss consciousness again
epidural hematoma: life-threatening
(blood between skull bone and dura mater)
diff vs. subdural hematoma (bleed from bridging cortical veins, gradual onset of headache and confusion). vs. subarachnoid hemorrage (aneurysm, severe headache)
define:
neuron cell body rounding, peripheral displacement of the nuclei, dispersion of Nissl substance to the periphery of the cells
“axonal reaction”, after sever of axon from the neuronal body. Severed axon is digested by Schwann cells. Neuronal cell body shows cellular edema (round, swollen, nuclei to the peripheral, Nissl substrance dispersed through the cell body - indicating increased synthesis of proteins to regenerate axon)
MS
年轻人， 双视，动眼神经障碍，反复发病，中间有几个月-1年间隙，
MS: neuronal demyelination, depletion of oligodendricytes, Dx by MRI, ↑ CSF IgG (autoimmune), which shows up as “oligoclonal bands” on protein electrophoresis
VB12-deficient neurodegeneration:
Cx?
affect the following 3 in spinal cord
1) dorsal column (bilateral loss of position/vibration sensation: gait abnormality - can’t walk, especially when eyes closed)
2) lateral CS (corticospinal) tracts: UMN signs (spastic paresis 痉挛性轻瘫), hyperreflexia, patholigic reflexes (Barbinski sign)
3) PNS axonal degeneration: numbness, parethesias
与ALS区别：ALS involves both UMN and LMN (lower motor neuron）
CN III function?
CN III: oculomotor nerve
2 types of fibers (with different blood supply) 2 functions:
1) somatic component: 受损lead to ptosis ; “down and out” gaze
2) parasympathetic fibers: sphincter of the iris and the ciliary muscle. Paralysis of these fibers causes a fixed, dilated pupil
pathway for pain/temperature sensation
1st N: DRG → 2nd N: dorsal horn , axon decussate in the ventral white commissure, ascend in the contralateral lateral funiculus → 3rd N: thalamus → 4th N: somatosensory cortex in the parietal lobe (顶叶）
Dx: young adult, slow relaxation of muscles (can’t release hands after hand-shaking, can’t release doornob), + cataracts, frontal boldness + gonadal atrophy
myotonic muscle dystrophy (肌强直性肌萎缩），
除了Ducchenne之外第二MC的肌萎缩
CTG trinucleotide repeats, AD, anticipation
Pick’s disease
profound atrophy of frontal /and temporal lobes,
diff vs. AD; dementia, inappropriate behavior, impaired judgement, lost problem-solving skills, dysarthria (构音障碍， damage of Broca’s speech area in frontal lobe)
lung cancer compresses which nerve to cause:
1。hiccups + dyspnea
2. shoulder pain
3. Horner’s syn
- phrenic N (膈神经， C3-C5)
- lung cancer at apex can invade the rami of the branchial plexus to cause shoulder pain
- Horner’s： ipsilateral miosis, ptosis, anhydrosiss; oculosympathethic nerve (眼交感神经）
opsoclonus (眼阵挛）- myoclonus (肌阵挛）syn is associated with ?
neuroblastoma, (N-Myc), MC extracranial neoplasma in children (~2 yrs)
Dx: cerebellum and/or retina angiomatoma, + cystic mass in the kedney, liver or pancrease
Von Hippel-Lindau disease
Sturge-Weber Syn
encephalotrigeminal angiomatosis (脑三叉神经血管瘤病,瑟志-韦伯综合征)颜面血管瘤综合征
congenital neurocutaneous disorder: cutaneous facial angioma, skin involvement overlies V1 and V2 area of the trigeminal N.
associated with mental retardation, seizures, hemiplegia, skull radiopacities (X光不透性）
TS or TBC (tuberous sclerosis)
AD, caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors,
特征：cutaneous facial angiofibromas (“butterfly lesion”)
visceral cysts in kidney, liver and pancrease; HAMARTOMAS (not angiomatous lesions! Dx from von Hipple-lindau). 心脏表现也为错构瘤
Seizures are a major clinic complication
paraneoplastic syn: caused by?
autoimmune
Mechanism for neuromuscular sym in CF?
recurrent pancreatitis → ↓ fat-soluble Vit (A, D, E, K) reobsorption → ↓ of Vit E antioxidative function → cell membrane damage, most prominent in neurons with long axons and RBC
↓ proprioception, hyporeflexia over the longer extremities, mild hemolytic anemia
Guillian-Barre syn
吉利刀片划伤了外周神经
autoimmune-mediated acute demyelination of the peripheral nerves. often preceded by a febrile illness and is strongly associated with Campylobacter jejuni (空肠弯曲杆菌）infection.
Cx: ascending muscle weakness and areflexia
Dx: pulmonary histology change
- Transudate in the alveolar lumen , 漏出液： Cardiogenic acute pulmonary edema (acute M
- scattered necrosis with alveolar Hemorrhage I)
- Pulmonary hemorrhage syndromes, Such as Goodpasture syndrome Wegener’s syndrome
