QB - DISEASES Flashcards
Burkitt lymphoma
t(8;14)
c-myc
CML
t(9;22) - Philadelphia chromosome
bcr-abl “enable things to occur rapidly = increase TYROSINE KINASE activity”
tyrosine kinase = initiator of many processes
ELEVATED WBCs and platelets
Mantle cell lymphoma
t(11;14)
cyclin D1 - promoter of G1 to S-phase transition of cell cycle (cancer!!)
CLL
Deletion of 13q
AML
M3 variant of AML
Auer rod
t(15;17)
Follicular lymphoma
t(14;18)
BCL2 - antiapoptosis
Li-Fraumeni
Autosomal dominant
mutation of p53 (tumor suppressor gene)
Sarcomas
Tumors = breast, brain, adrenal cortex
Wiskott-Aldrich (triad)
- eczema
- Recurrent infections
- Thrombocytopenia
Hemolytic Uremic Syndrome (HUS) symptoms; what organisms cause HUS?
- Microangiopathic hemolytic anemia (conjunctival pallor = anemia)
- Thrombocytopenia
- Acute renal failure
Due to Shiga toxin-producing organisms: Shigella dysenteriae or E. coli O157:H7
Aplastic anemia
Bone marrow damaged - deficiency in all 3 blood cell types
Chloramphenicol use
Sickle cell disease (parvovirus B19)
DiGeorge syndrome
Maldevelopment of 3rd & 4th pharyngeal pouches
Hypoplasia of thymus & parathyroids
Cardiac & aortic arch abnormalities
Characteristic facies
Chediak-Higashi syndrome
Oculocutaneous, hair, skin albinism
Peripheral neuropathy
Immunodeficiency (phagocyte-phagosome-lysosome fusion defect) –> recurrent pyogenic infections
Ataxia-telangiectasia syndrome
Progressive ataxia w/ telangiectasia + immunodeficiency (combined defect of B&T-lymphocytes)
CO poisoning
No effect on PaO2 (partial pressure of oxygen dissolved in plasma)
Reduces O2 unloading from Hgb and prevents O2 binding to Hgb
Multiple Myeloma
Plasma cells infiltrate bone marrow - “clock face” nuclear chromatin
Features:
1. Anemia (due to infiltration of plasma cells and inadequate hematopoiesis)
2. Bone resorption (IL-1 activates osteoclasts), IL-6
3. Hypercalcemia (due to bone destruction)
4. Susceptibility to infection (M protein, Ig light chains BENCE JONES protein); Hyperimmunoglobulinemia –> Rouleaux formation –> increased ESR
5. AL amyloid (“apple-green birefringence w/ Congo red stain)
6. Renal failure (deposition of amyloids in kidney tubules, heart, tongue, nervous system)
Diarrhea (parasitic – eosinophilia seen)
- Strongyloides
- Ancylostoma
- Ascaris
- Toxicara
- Trichura
- Trichinella
Diarrhea (bacterial)
EIEC or Shigella – pus + RBC
EHEC (O157:H7) – NO pus - ONLY RBC!
Mycoplasma pneumoniae
“Walking pneumonia”
Anemia due to RBC lysis via COLD agglutinins (share antigens similar to RBCs)
Stevens-Johnson syndrome + joint pain sequelae
Requires cholesterol to grow (doesn’t have peptidoglycan layer)
Chest CT looks like severe pneumonia even though patients don’t seem as sick
CMV
DS-DNA enveloped virus
Opportunistic
Transplant patient
Enlarged, centrally located epitherlial cell + INTRANUCLEAR CYTOPLASMIC inclusions
Haemophilus influenza
Require Factor X (hematin) and V factor (NAD+) to survive
Can be grown on medium w/ S. aureus or on chocolate agar
Diff. btwn Staph and Strep
Catalase + –> STAPH
Corynebacterium diphtheriae
AB exotoxin
Toxin-mediated disease
E. coli
Conjuation via bacterial pili
Grows on MacConkey and EMB (eosin methylene blue) agar
Gram -
Neonatal meningitis (K-1 antigen)
Group B Strep (GBS)
1 Cause of neonatal meningitis
Others:
Listeria
Klebsiella
H. influenzae (type b)
E. coli
Enterobius vermicularis
Scotch tape test
Perianal itching (at night)
Albendazole/Mebendazole
Pyrantel pamoate (pregnant pts.)
Loa loa
Wuchereria bancrofti (lymphatic filaris)
Diethylcarbamazine
Strongyloides sterocoralis (strongyloidiasis)
Onchocerca volvulus (onchocerciasis)
Ivermectin
Trypanosoma cruzi (Chagas disease)
Nifurtimox
Schistosoma (schistosomiasis)
Clonorchis sinensis (clonorchiasis)
Paragonimus westermani (paragonimiasis)
Praziquantel
Hemolytic Uremic Syndrome (HUS)
E. coli 0157:H7
Occurs in children UNDER 10
Shiga like toxin
Contaminated ground BEEF
Bloody diarrhea
Diarrhea (FOOD consumption)
S. aureus - custard/mayo/processed salted meats
Preformed toxins - WATERY diarrhea (not bloody) - RAPID symptoms due to preformed toxins (resolves in 24hrs)
Bacillus cereus - fried rice
Vibrio parahaemolyticus - raw oysters - HIGH VOLUME, WATERY diarrhea (like cholera)
Salmonella - raw egg/raw chicken
Clostridium botulinum - improperly canned foods
Histoplasmosis in HIV patient
Pulmonary infiltrates w/ HILAR LYMPHADENOPATHY
Oval/round yeasts within macrophages (bone marrow slide)
Sabouraud’s agar = hyphae
HEPATOSPLENOMEGALY = likes reticuloendothelial system
Histoplasmosis - Mississippi & Ohio River Valley
Coccidioides immitis
Southwest US (Arizona) - San Joaquin Valley fever
Spherules rupture –> release endospores
Lung disease -> meningitis (HIV pts.)
Cryptococcus neoformans
Pigeon droppings
MENINGITIS + pulmonary infections (HIV pts.)
Budding yeasts w/ thick capsules
Stains red on mucicarmine stain - use bronchopulmonary washings
Opportunistic
CSF findings w/ India ink - confirms diagnosis
Peripheral clearings “halos” due to think polysaccharide capsules
Aspergillus fumigatus
Colonize old lung cavities (TB patients)
Hemoptysis
Opportunistic mycoses
Candida albicans
A. fumigatus
Mucor & Rhizopus
Clostridium perfringens
Gram + lives in soil
Anaerobic environment
Toxin = phospholipase that attacks cell membranes
Myonecrosis - GAS GANGRENE
Late-onset food poisoning: Transient watery diarrhea
Polyarthritis
Gonorrhea
Rheumatic fever
Strep pyogenes (group A)
Meningitis
M. tuberculosis
Acanthamoeba
Cryptococcus neoformans
Strep penumoniae
Lobar consolidation on CXRay
Klebsiella pneumoniae
Alcoholic coughing up “currant jelly sputum”
L. pneumophilia
Needs L-cysteine-supplemented agar
Coxiella burnetii
Q fever
Mild pneumonia symptoms
Contaminated animal hides
Pneumocystis jiroveci
Fungus in HIV+ patients
Ground glass infiltrates on CXRay
Herpes simplex 2
Multinucleated giant cells
Pinkish-purple intranuclear inclusions (Cowdry type A bodies)
Treat w/ Acyclovir, Valacyclovir, Famciclovir
Treponema pallidum
Gram - spirochete
Chancre that heals without treatment within few weeks
Haemophilus ducreyi
Tender, red papule on external genitals - PAINFUL!
Chlamydia trachomatis
Lymphogranuloma venerum (LGV)
PainLESS ulcers –> painful inguinal lymphdenopathy & ulceration (later progression)
Actinomyces israelii
Cervicofacial actinomycosis following dental procedure (oral trauma)
Slow growing/firm feeling abscess in face/neck region
Forms “sulfur granules”
Penicillin + surgical debridement
Rocky Mountain Spotted Fever
Palmoplantar erythematous macules - petechial eruption
Headache, fever, conjunctival hyperemia
Doxycycline
Cutaneous anthrax
Local edema + papule at inoculation site
Painless necrotic wound + black eschar
Ciprofloxacin
Pasteurella multocida
Oral flora of cats + dogs (humans get infected w/ cat bite)
Strep penumoniae (virulence factors)
MAJOR: polysaccharide capsule that INHIBITS phagocytosis by macrophages + PMN leukocytes
“Quellung reaction” - antibodies to capsule causes capsules to swell –> destruction of capsules renders S. pneumonia NONvirulent
Additional factors: pneumolysin - suppresses phagocyte’s oxidative burst; adhesin
Alpha-hemolytic (incomplete “green” hemolysis on blood agar)
Aspergillus fumigatus
Mucormycosis - diabetes mellitus + diabetic ketoacidosis
Immunocompromised (opportunistic infection)
Herpes simplex 1 (HSV-1)
CHILDREN - 1 to 3 yrs
Gigivostomatitis (swollen gums, ulcerative lesions)
Lymphadenopathy
Intranuclear inclusions
Enveloped DS DNA virus
Measles also infect this age group and lesions also have intranuclear inclusions but have BLUISH-GRAY KOPLIKE spots on buccal mucosa
IntraAbdominal abscess
B. fragilis
E. coli
—-
S. aureus - abscess on skin
Actinomyces - abscess in cervicofacial region/abdominal cavity
Candida albicans - perforation of proximal bowel (peptic ulcer)
E. histolytica - amebic liver abscess
Borrelia burgdorferi
Lyme disease - Ixodes tick
Red macules that are ring-shaped w/ CENTRAL clearing - ERYTHEMA CHRONICUM MIGRANS
Treponema pallidum
Condyloma lata - generalized macular eruption
Leptospira interrogans
Weil’s syndrome: hepatic dysfunction –> conjugated hyperbilirubinemia, renal dysfunction, thrombocytopenia, bleeding
Bartonella henselae
Cat scratch fever
Lymphadenopathy, malaise, fever
Antibiotic resistance
Penicillin binding protein (PBP) - MRSA
Resistance including penicilinase-stable penicillins (oxacillin, nafcillin, methicillin)
Mutation in RNA polymerase - Rifampin resistance
Decrease in levels of drug accumulation (decreased uptake/increased efflux) = Tetracycline + Sulfonamides
Mutation in DNA gyrase = quinolone resistance
Clostridium botulinum
Spore forming ANAEROBIC bacillus
Botulinum toxin prevents presynaptic release of Acetylcholine (Ach) –> muscular relaxation
Toxin used as therapy to treat focal dystonias, achalasia (lower esophageal sphincter), and muscle spasms
Hypervariable pili
Neisseria meningitidis
N. gonorrhoeae
Staph aureus
IgG binding outer membrane protein (protein A)
Protein A binds Fc portions of IgG –> prevents opsonization, phagocytosis, complement fixation
Corynebacterium diphtheriae
Intracellular polyphosphate granules
Respiratory tract infections (CHILDREN)
- Nasopharyngitis (Rhinovirus, Influenza, Coronavirus)
Congestion, discharge, sneezing, sore throat - Laryngotracheitis/Croup (Parainfluenza)
Barking cough, stridor - Diphtheria (Corynebacteriu diphtheriae)
Pseudomembrane - Epiglottitis (H. influenzae)
Dysphagia, drooling - Bronchiolitis (RSV)
Wheezing
Togavirus
German measles (Rubella)
Eastern & Western equine encephalitis
Parvovirus
Aplastic crises in sickle cell anemia
Erythema infectiosum (5th disease)
Huydrops fetalis
Calicivirus (Norwalk virus)
Viral gastroenteritis
Parainfluenza virus
Brassy, BARKING cough (CROUP)
Viral laryngotracheitis
Paramyxoviridae
Toxoplasma gondii
Obligate intracellular
HIV patients
Encephalitis - multiplenecrotizing brain lesions
Ring-enhancing lesions in both hemispheres
Pyrimethamine & sulfadiazine
HIV - gag, pol, env
gag = nucleocapside proteins p24 and p7
pol = reverse transcriptase
env = envelope and gp120 and gp41
CMV vs EBV
EBV = mononucleosis
Symptoms: fever, malaise, myalgia, atypical lymphocytosis, elevated liver transaminases, heterophil antibodies (causes RBC to agglutinate)
CMV = similar symptoms to EBV except…
Don’t see heterophil antibodies
CMV in immunocompromised:
Severe retinitis, pneumonia, esophagitis, colitis, and/or hepatitis.
Parvovirus
Erythema infectiosum (fifth disease) in children
Bright red rash on cheeks 5-7 days after fever
In adults: arthritis resembing rheumatoid arthritis – but it resolves spontaneously
Rheumatic fever
migratory pain/swelling in large joints
fever, carditis, choreaform movements, erythema marginatum
occurs a few weeks after STREP pharyngitis
SLE
Malaise, weight loss
MALAR facial rash
arthralgias in young women
Anthrax
Widened mediastinum (hemorrhagic mediastinitis)
Wool-sorting business
Gram + rods
Antiphagocytic D-glutamate capsule
Serpentine/medusa head on appearance
Intracellular polyphosphate granules
Loeffler medium stain w/ methylene blue
Corynebacterium diphtheriae
Pertrichous flagella
Proteus mirabilis
Cat Scratch disease
Bartonella henselae
Focal lymphadenopathy
Bacillary angiomatosis in immunocompromise pts. (red-purple papular skin lesions)
Hemolytic Uremic Syndrome (HUS)
E. coli O157:H7
Microangiopathic hemolytic anemia
Thrombocytopenia
Renal insufficiency
Reiter’s syndrome
HLA-B27 positive reactive arthritis
Urethritis
Conjunctivitis
Chlamydia, Salmonella, Shigella, Yersinia, Campylobacter infections
Condylomata acuminata
Genital warts
HPV 6 + 11
Xeroderma pigmentosum
Pigmented dry skin
Lack of DNA excision repair - can’t repair DNA in skin following UV damage
Erythema, scaling, hyperpigmnetation, lentigo (pigmented papules)
Related: Fanconi anemia, Bloom syndrome (hypersensitivity to UV damage and chemo agents)
Granulomatous diseases (10)
- Mycobacterium tuberculosis
- Histoplasmosis, Coccidiodomycosis
- Treponema pallidum (syphilis)
- M. leprae (leprosy)
- Bartonella henselae (Cat scratch disease)
- Sarcoidosis
- Crohn’s disease
- Granulomatosis with polyangiitis (Wegener’s)
- Churg-Strauss syndrome
- Berylliosis, silicosis
Granulomatous disease mechanism
TH1 cells –> gamma-interferon secretion –> activates macrophages –> produces TNF-alpha –> granuloma formation
Anti-TNF drugs cause sequestering granulomas to break down –> disseminated disease
Tuberous Sclerosis
Facial angiofibroma
Seizures
Mental retardation
Tuberous Sclerosis (associated neoplasms)
Giant cell astrocytoma
Renal angiomyolipoma
Cardiac rhabdomyoma
Small cell lung carcinoma
Paraneoplastic syndrome
Cushing’s (ACTH), ADH (SIADH), Anti-Ca2+ channels (Lambert-Eaton)
PKU
Mental retardation
Hypopigmentation (skin, eyes, basal ganglia – substantia nigra, locus ceruleus, vagal nucleus dorsalis)
“Mousy” or musty odor
Phenylalanine cannot be converted to tyrosine; lack of phenylalanine hydroxylase or cofactor tetrahydrobiopterin (BH4)
Accumulation of phenylalanine in brain
Mental retardation
Seizures
Disease seen in PKU (fair skinned, blonde hair, blue eyes, musty odor pt.)
Chvostek’s sign
Facial muscle contraction elicited by tapping on facial nerve (anterior to ear) – occurs when Ca2+ levels LOW (less than 7.0mg/dL)
Primary hypoparathyroidism = loss of parathyroid tissue during thyroidectomy
Polycystic ovarian syndrome
PERSISTENTLY elevated estrogen, androgen, LH levels
Hyperandrogenism, Anovulation, Oligomenorrhea, multple ovarian cysts
Theca cell hyperplasia –> excess androgens (acne, hirsutism, male pattern balding, virilization)
Obesity, insulin resistance, dyslipidemia –> increase risk of diabetes and cardiovascular disease
Excess estrogen - thickened endometrium - increase risk of developing endometrial hyperplasia & carcinoma
Treatment w/ weight loss & oral contraceptives
Addison’s disease
Primary defect in adrenal coritosl – NO feedback inhibition of anterior pituitary pro-opiomelanocortin (POMC)
POMC continues to make ACTH and MSH (melanocyte stimulating hormone) –> hyperpigmentation
TRH (thyroid releasing hormone) defect
Lack of TSH and prolactin
Lechithinase (alpha toxin)
C. perfringens
destroys lecithin (cell phospholipid membrane)
destruction of cells –> necrosis/hemolysis, cell death
Gestational diabetes mellitus
HUMAN PLACENTAL LACTOGEN
Similar to GH and prolactin - causes INCREASE in insulin resistance to increase serum glucose; increase serum glucose shunted to developing fetus for increasing energy requirements
Fracture of midshaft of humerus
Radial nerve + deep brachial artery damage
Loss of extensors in forearm and at wrist
Fracture to surgical neck of humerus
Axillary nerve + Anterior circumflex humeral a.
Fracture to supracondylar humerus
Brachial artery
Primary adrenal insufficiency vs. Secondary/Tertiary (pituitary/hypothalamus)
Primary - hyponatremia, hyperkalemia, hypochloremia, metabolic acidosis
Secondary/Tertiary - do NOT have hyperkalemia or metabolic acidosis; WILL respond with serum cortisol production when exogenous ACTH is administered
Hyponatremia, hypokalemia, hypochloremia w/ metabolic alkalosis
Diuretic use (contraction alkalosis – increased bicarb absorption)
Positive Trendelenburg
Superior gluteal n. = weakness in gluteus medius and minimus; walk w/ waddling gait/characteristic limp
Difficulty rising from seated position
Difficulty climbing stairs
Inferior gluteal nerve (gluteus maximus)
Lambert-Eaton myasthenic syndrome and myasthenia gravis also have proximal muscle weakness
Deficit in thigh adduction
Obturator nerve
Loss of knee reflex (extension of leg at knee)
Loss of anterior thigh sensation
Femoral n.
Knee flexors (hamstrings)
Sciatic n.
21-hydroxylase deficiency
MOST COMMON congenital adrenal hyperplasia
Can’t make aldosterone or cortisol (get buildup of 11-deoxycorticosterone and 11-deoxycortisol)
ACTH is elevated bc there’s not feedback inhibition from cortisol (cortisol isn’t being made)
Test for 17-OH progesterone (buildup of precursor products)
Accumulating aldosterone and cortisol precursors shunted to androgen pathway –> females have AMBIGUOUS genitalia (VIRILIZATION)
Males have normal genitalia - have symptoms later w/ SALT-WASTING or precocious puberty
Desmolase
Conversion of cholesterol to pregnenolone (absence of this enzyme results in complete absense of steroid hormones) = INCOMPATIBLE w/ life
17-hydroxylase deficiency
Can’t make androgens - everything diverted to make mineralcorticoids (aldosterone)
Salt retention –> HTN
ALL phenotypically “FEMALE” due to impaired androgen synthesis
Deficiency of DHT (in utero)
Androgen insensitivity syndrome
PTH
Increase osteoclastic bone resorption
Increase DISTAL tubular absorption of calcium
Increase formation of 1,25-dihydroxy vitamin D (via upregulation of 1-alpha hydroxylase)
1,25-dihydroxy vitamin D increases GI absorption of Ca2+
SECONDARY hyperparathyroidism:
Patients w/ RENAL FAILURE – DECREASED formation of 1,25-dihydroxy vitamin D –> decreased absorption of Ca2+
RENAL FAILURE - elevated phosphorous (can’t be excreted) –> increase PTH hormone “secondary hyperparathyroidism” bc PTH is antagonistic to phosphorous (will cause elimination of phosphorous)
PTH-independent hypercalcemia
Humoral hypercalcemia of malignancy
Vitamin D toxicity
Excessive ingestion of Ca2+
Thyrotoxicosis
Immobilization (Ca2+ is resorbed from inactive bones)
Adrenal crisis
“Shock-like state”
Hypotensive, tachycardic, hypoglycemic
Adrenal insufficency (vomiting, abdominal pain, weight loss, hyperpigmentation due to MSH overstimulation)
Patients w/ adrenal insufficiency - can’t make glucocorticoids essential for cardiovascular + metabolic adaptations during stressful situations
Inactive FSH receptors
Lack of spermatogenesis and inhibin B production
LH release testosterone from Leydig cells (testosterone feeds back to inhibit LH)
FSH releases inhibin B from Sertoli cells (inhibin feeds back to inhibit FSH)
FSH does NOT make testosterone but is responsible for ANDROGEN-BINDING protein which binds testosterone and elevates local testosterone that is necessary for spermatogenesis
Lambert-Eaton myasthenic syndrome (LEMS)
1/2 patients have associated malignancy: SMALL CELL lung cancer
Similar symptoms to myasthenia gravis: diplopia, ptosis, dysarthria, dysphagia
Differences:
LEMS - hyporeflexia/areflexia, autonomic symtpoms, classic incremental response to repetitive stimulation
Myasthenia gravis
Thymoma & thymic hyperplasia (appears as ANTERIOR mediastinal mass)
Autoimmune condition - weakness of facial, periocular, bulbar, and pelvic girdle muscles
Ascending muscle weakness (demyelination) - T lymphocyte and macrophage infiltration
Campylobacter infection
Polymyositis
Idiopathic inflammatory myopathy
Bilateral proximal weakness
Elevated creatine kinase (CK)
Polymyalgia rheumatica (PMR)
Sudden onset stiffness, pain, tenderness of musculature (shoulders, hips, neck, torso)
Elevated ESR
ALS
UMN involvement (hyperreflexia, spasticity) coupled w/ LMN involvement (atrophy, fasiculations)
Multiple sclerosis
Autoimmune: 20-30yr old females
Increased IgG in CSF
Demyelinating lesions in brain/spinal cord
Optic neuritis: sudden loss of vision w/ painful eye movements
Cerebellar damage: intention tremor
Guillan-Barre
Acute postinfectious polyneuropathy
Nonspecific prodromal malaise/nausea FOLLOWED by progressive ascending paralysis
Bitemporal hemianopsia (endocrine effect)
Pituitary tumor - PROLACTINOMA
Prolactin inhibits entire GnRH-LH/FSH axis
Impotence in men/Amenorrhea in women (hypogonadtropic amenorrhea)
Men = decreased GnRH, decreased FSH, decreased LH, decreased testosterone
Dopamine inhibits prolactin via D2 dopamine receptor on lactotrophs (damage to hypothalamus –> hyperprolactinemia)
Sheehan syndrome
Postpartum hemorrhage (hypotension) –> ischemic necrosis to pituitary (that enlarged and became more vascular during pregnancy)
Panhypopituitarism:
Woman can’t lactate - prolactin deficiency
Hypothyroidism = excessive weight loss and malaise
Hypocortisolism
Autoimmune hypophysitis (inflammation of pituitary)
Acute presentation: headaches, visual field deficits
Also low cortisol
Occurs late pregnancy or early postpartum
Pituitary apoplexy
Hemorrhage in preexisting pituitary adenoma - emergency!!
Acute, severe headache, ophthalmoplegia, altered sensorium
Vascular deposition of circulating immune complexes
SLE, Rheumatoid arthritis, connective tissue
Type I hypersensitivity
IgE mediated
IgE produced by B lymphocytes + plasma cells
Specific for allergens (IgE) – crosslinking of IgE molecules on surface of basophils and mast cells –> degranulation of HISTAMINE
SIADH
Hyponatremia + lung mass (small cell carcinoma of lung**)
SIADH –> excessive water reabsorption –> HYPERVOLEMIA renin/angiotensin stimulates natriuretic peptides –> excrete Na+ in urine (hyponatremia)
Patients have normal body fluid volume but LOW plasma osmolality (euvolemic hyponatremia)
Low plasma sodium & osmolality, inappropriately concentrated urine (even though there’s no Na+ around to cause concentration of urine), increased urinary sodium, and normal body fluid volume
Estrogen effect on T4
Estrogen increases amount of TBG (thyroid binding globulin) –> increase level of total T4 and T3
Free thyroid hormones = stay SAME so patients are euthyroid w/ normal TSH
Increases in circulating T4 seen in pregnancy, oral contraceptives, hormone replacement therapy
Psoriasis
Hyperparakeratosis, acanthosis, rete ridge elongation
Mitotic activity above basal cell layer
Reduced/absent stratum granulosum
Dermatitis herpetiformis
Pruritic vesicles/plaques on extensor surfaces
Gluten enteropathy
Erythema nodosum
Painful, reddish nodules on shins
Oral contraceptives, Strep pharyngitis, IBS, Sarcoidosis
Fracture of femoral head & neck
Medial femoral circumflex artery damage –> avascular necrosis of femoral head
Recurrent nosebleeds, swollen gums, ecchymoses, hyperkeratosis, ulcer on lower extremity
Vitamin C deficiency (scurvy) = decreased connective tissue strength
Vitamin C needed to hydroxylate proline + lysine via prolyl and lysyl hydroxylases
PID
Chlamydia/gonorrhea
PID –> ectopic pregnancy
Increase changes of ectopic pregnancy due to previous abortions, exposure to DES
Yeast infection risk factors
Antibiotic use recently
Diabetes
Kid w/ SORE THROAT + rash
Strep infection causing scarlet fever
PYROGENIC toxin
—
Endotoxin: Gram - sepsis
M protein: Rheumatic fever*
Alpha toxin: C. perfrigens
Crohn’s disease in relation to bladder
Causes fistula w/ bladder
Umbilicated, flesh-colored papules in kid (red dot in middle of cell)
Molluscum contagiosum
Pox virus
Otitis externa (tenderness when tugging on outside of ear)
Pseudomonas - “blue green” - wet
Associated w/ water (hot tubs, burns)
CSF pathway through ventricles
Lateral –> 3rd ventricle via FORAMINA OF MONRO
3rd –> 4th ventricle via CEREBRAL AQUEDUCT (of Sylvius)
4th ventricle –> subarachnoid space via FORMINA of LUSCHKA (lateral)/MAGENDIE (medial)
CSF return to venous circulation via ARACHNOID VILLI (granulations)
Types of hydrocephalus
Communicating - blockage in subarachnoid space (fibrosis); no blockage in brainstem
Normal pressure - CSF NOT absorbed
Hydrocephalus ex vacuo - increase CSF VOLUME
Pseudotumor cerebri: overweight young females - decreased CSF outflow at arachnoid villi
Coarctation of aorta
Turner syndrome, bicuspid aortic valves
BP elevated proximal to coarctation, BP decrease distal to coarctation
Duodenal atresia
Down syndrome
Bilious vomiting without abdominal distention - 1st day of life! (duodenal lumen fails to recanalize)
Polyhydramnios
Renal agenesis in utero
Potter syndrome
Oligohydramnios/facial dysmorphism
Pulmonary hypoplasia
Ebstein’s anomaly
ATRIALIZED right ventricle (downward displacement of tricuspid valve)
maternal exposure to LITHIUM*
Failure of neural tube fusion
a-fetoprotein (AFP) + acetylcholinesterase levels ELEVATED
ANTERIOR neuropore:
- encephalocele (herniation of brain tissue through cranial defect)
- anencephaly (absence of brain/calvarium)
POSTERIOR neuropore (more common):
- spina bifida occulta
- meningocele
- meningomyelocele
Vertical vs. Horizontal diplopia
Vertical diplopia (walking downstairs): CN IV (trochlear)
Horizontal diplopia: CN VI (abducens) – also have esotropia (inward deviation of eye)
Lesion of medial longitudinal fasciculus (MLF)
Internuclear ophthalmoplegia
Impaired horizontal eye movement; weak ADDUCTION of affected eye w/ simultaneous nystagmus of CONTRA eye (trying to compensate)
Progressively weakening diaphragmatic contractions on inspiration
Neuromuscular junction pathology - MYASTHENIA GRAVIS
Rapid diaphragmatic muscle fatigue - restrictive lung/chest wall disease
Guillain-Barre
Acute demyelinating disease (following infection, immunization, allergic reaction)
Antibodies to some infectious agent that contain gaglioside-like substance cross-react w/ ganglioside components of MYELIN –> SEGMENTAL DEMYELINATION & ENDONEURAL INFLAMMATORY INFILTRATE
Ascending muscle weakness (following respiratory or GI infection)
Campylobacter jejuni
Absence of deep tendon reflexes (DTRs)
Paralysis of respiratory muscles - fatal!
CNVII - Bell’s palsy (if cranial nerves affected)
Werdnig-Hoffman
LMN
“floppy child” syndrome
Lambert-Eaton
Resembles myasthenia gravis
Associated w/ small cell lung carcinoma
Autoantibodies w/ presynaptic Ca2+ channels – no release of Ach
Differentiate Myasthenia gravis & Lambert-Eaton
Both weakness of proximal muscles
MG:
Ptosis, Diplopia
Thymoma risk
Antibodies against ACh receptors
Nerve stimulation studies - DECREASE response
Weakness of muscles WORSE w/ exertion
L-E:
Pre-existing malignancy
Antibodies against pre-synaptic Ca2+ channels
Nerve stimulation studies - INCREASE response
Weakness of muscles BETTER w/ exertion and exercise (better at the end of the day)
Subacute combined myelopathy
Vitamin B12 deficiency
DORSAL COLUMNS + LATERAL CEREBROSPINAL tracts affected
loss of position/vibration sensation, spastic paresis, ataxia
Primary CNS tumor in AIDS patients
CNS lymphoma (diffuse large B-cell lymphoma) - CD20 + CD79a
EBV related - poor diagnosis
Meningiomas
Adjacent to brain surface + attached to dura mater
Craniopharyngiomas
Suprasellar region - can be CALCIFIED
Endocrinopathies (hypopituitarism)
Intracranial schwannomas
Cerebellopontine angle
CN VIII compression symptoms (hearing loss, tinnitus, loss of balance)
Fragile X syndrome
mild, severe mental retardation (second most common cause of mental retardation; #1 is Down Syndrome)
long thin face, prominent forehead + jaw
macroorchidism (large testes!)
FMR-1 gene (familial mental retardation gene-1)
CGG trinucleotide repeat
hypermethylation of CYTOSINE bases – gene inactivated
DNA mismatch repair gene DEFECT
Lynch syndrome
increased risk of hereditary non-polyposis colorectal cancer (HNPCC)
Chromosomal instability disorders
- Xeroderma pigmentosum
- Ataxia-telangiectasia
- Fanconi’s anemia
- Bloom syndrome
Fulminant meningococcemia
Waterhouse-Friderichsen syndrome
bilateral adrenal hemorrhage –> adrenal insufficiency –> hypotension –> death
DIC, shock
N. meningitidis
pharynx –> blood –> choroid plexus –> meninges
Route of infection for:
H. influenzae
S. pneumoniae
S. aureus
M. tuberculosis
- H. influenzae: pharynx –> lymphatics –> meninges (infants/children)
- S. pneumoniae: middle ear –> contiguous tissues –> meninges
- S. aureus: skull trauma –> leaking CSF –> meninges (get abscess)
- M. tuberculosis: lung focus –> blood –> meninges
Rabies encephalitis
Restlessness, agitation, dysphagia –> progressing coma –> death
Vaccine: KILLED rhabdovirus strains
Rabies virus = -ssRNA
PKU
Lack of phenylalanine hydroxylase
Inability to convert phenylalanine to tyrosine
TYROSINE becomes an essential aa
excess phenylalanine inhibits tyrosinase (synthesis of melanin from tyrosine) –> fair skinned people
Lead poisoning (enzymes affected)
- d-Aminolevulinate dehydratase
- Ferrochelatase
d-ALA (d-aminonlevulinic acid) and protophorphyrin IX accumulates
d-Aminolevulinate synthase (rate limiting reaction in HEME BIOSYNTHESIS)
Deficiency in uroporphyrinogen I synthase
Acute intermittent porphyria
Abdominal pain + neuropsychiatric symptoms
Deficiency in uroporphyriongen decarboxylase
Most common porphyria: Porphyria cutanea tarda (PCT)
Uroporphyrinogen accumulates in urine; mild photosensitivity
Bilirubin glucuronyl transferase
Conjugation of bilirubin
Niemann-Pick
deficiency of sphingomyelinase –> sphingomyelin accumulates in phagocytes –> “foamy histiocytes”
loss of previously acquired motor capabilities
cherry-red macular spot (similar to Tay Sachs)
hepatosplenomegaly
Tay Sachs
deficiency in hexosaminidase A –> GM2 ganglioside accumulation
Hurler syndrome
deficient in alpha-L-iduronidase
accumulation of heparan sulfate + dermatan sulfate
Gaucher disease
deficient in glucocerebrosidase
accumulation of glucocerebroside in phagocytes
Von Gierke disease
deficiency in glucose-6-phosphatase
Pompe disease
deficiency in lysosomal alpha-1,4-glucosidase
Fabry disease
deficiency in alpha-galactosidase A –> accumulation of ceramide trihexoside
Progression to RENAL failure
Angiokeratomas
Hypohidrosis
Acroparesthesia (burning neuropathic pain in extremities)
Lesch-Nyhan syndrome
deficiency of hypoxanthine guanine phosphoribosyl transferase (HGPRT)
disorder in uric acid metabolism
Spasticity
Choreoathetoid movements (involuntary movement spasms + writhing movements)
SELF MUTILATION
Neuroblastoma
located in adrenal medulla
non-rhythmic conjugate eye movements w/ myoclonus
increased N-myc gene copies
retroperitoneal mass
Hypothalamic nuclei (functions)
- Ventromedial - satiety (leptin stimulated)
- Ventrolateral - hunger
- Anterior - cooling
- Posterior - heating
- Arcuate - dopamine secretion (inhibits prolactin); GHRH and gonadotropin release
- Paraventricular - ADH and oxytocin releasing, CRH, TRH
- Supraoptic - secretion of ADH and oxytocin
- Suprachiasmatic - circadian rhythm, pineal gland function
CN IV lesion
internal rotation, depression, abduction
lesion – vertical & torsional diplopia, eye deviates upwards
CN VI lesion
abduction
lesion – horizontal diplopia, eye deviates medially
Hydrocephalus in infants
Increased head circumference, enlarged ventricles
Muscle hyperreflexia and hypertonicity due to UMN damage due to stretching of periventricular pyramidal tracts
Chronic granulomatous disease (CGD)
X-linked
inability of phagocytes to synthesize NADPH oxidase - can’t have lysosomal oxidative burst
pts. suffer recurrent infections from catalase-positive organisms: staphylococci
Alzheimer disease
Decreased acetylcholine level (lack of choline acetyltransferase)
areas affected:
basal nucleus of Meynert - memory/cognition
Hippocampus - formation of new memories
Locus ceruleus
Panic attacks, panic disorders
Caudal pontine central gray matter - contain NE
Nucleus caudatus (atrophy)
Huntington’s
NMDA receptors depleted in striatum
Raphe nuclei
Serotonergic
Anorexia, depression, sleep disorders
Global cerebral ischemia
due to cardiac arrest –> cessation of blood flow –> severe hypoperfusion
Ischemia >5mins causes irreversible damage to neurons
Watershed areas of anterior, middle, and posterior cerebral aa.
Bilateral wedge-shaped bands of necrosis over cerebral convexities, lateral to interhemispheric fissure
Irreversible injury in neuron
“red neuron”
12-24 hours after injurious event
shrinkage of cell body
eosinophilia of cytoplasm
pyknosis of nucleus
loss of Nissl substance
Syringomyelia
Cyst in spinal cord
- lateral spinothalamic tract (bilateral loss of P&T)
- motor neurons of anterior horns: LMN (flaccid paralysis, atrophy of intrinsic muscles)
Lateral corticospinal tract lesion vs. Anterior horn involvement (spinal cord)
Lateral corticospinal tract: UMN lesion
Anterior horn: LMN
ALS (amylotrophic lateral sclerosis) has BOTH!
Anterior spinal artery syndrome
Compression/occlusion of artery
COMPLETE loss of strength below level of injury
Loss of pain & temperature
STILL has vibratory senses
Increased AFP
Neural tube defects
Down’s syndrome
Decreased AFP
Excessive skin at posterior neck
VSD and duodenal atresia
endocardial cushion defect
TE fistula
Slanted palpebral fissues,
Single transverse palmar crease
Flat facies
Edwards syndrome vs. Patau syndrome
Edwards - 18- prominent occiput, microagnathia (small jaw), low set ears, small mouth, overlapping fingers-clenched hands, severe mental retardation (usually die by 1yr)
Patau - 13 - ENTIRE HEAD affected (microcephaly - small head!), polydactyly, umbilical hernia, holoprosencephaly (forebrain doesn’t divide into 2 hemispheres), cleft lip – occurs secondary to nondisjunction during meiosis I
“Common cold”
Coronavirus, rhinovirus, adenovirus
Achondroplasia
Fibroblast growth factor receptor 3 (FGF-3)
Autosomal dominant
Spontaneous mutations w/ advanced paternal age
Shortened limbs, normal face and normal torso
1/3 chance normal baby from 2 affected parents (2/3 chance baby has symptoms)
Aseptic meningitis
Enteroviruses - coxsackievirus, echovirus, poliovirus, enterovirus
Bacterial meningitis (adults)
S. pneumoniae, N. meningitidis
Alterations in mental status/seizures
Neutrophilic pleocytosis, LOW glucose, HIGH protein
Alcoholic given IV dextrose before thiamine
Wernicke’s encephalopathy can occur bc THIAMINE is coenzyme for PYRUVATE DEHYDROGENASE in glucose metabolism
Pt. given glucose with no thiamine –> glucose not metabolized –> necrosis of brain = MAMILLARY BODIES (emotion and memory via Papez circuit)
Thalamic syndrome
Vascular lesion –> damage to thalamic VPL and VPM nucleus –> CONTRA sensory loss (lower and upper extremities, face)
Proprioceptive defects –> unsteady gait + falls
Caudate nucleus lesion
Transient hemiparesis (weakness on one side of body)
Frontal lobe symptoms (inattentiveness, forgetfulness)
Internal capsule lesion
Posterior limb separates globus pallidus and putamen from thalamus
Carries corticospinal MOTOR and somatic SENSORY fibers + visual and auditory fibers
Pons lesion
Coma
Bilateral paralysis
Huntington’s
CAG trinucleotide repeats
Anticipation (offspring develop diseases earlier)
Autosomal dominant
Atrophy of caudate nucleus
Parinaud syndrome
Tumor of pineal gland
GERMINOMAS most common tumor of pineal gland
Children/adolescents - mostly MALEs
- precocious puberty (B-hCG production)
- Obstructive hydrocephalus (due to tumor compressing aqueduct)
- Parinaud syndrome: PARALYSIS of upward gaze and convergence
Pontine hemorrhage/tumor
“locked in” syndrome = spastic quadriplegia and paralysis of most cranial nerves
Lesions of medulla
- Lateral medullary syndrome:
Wallenberg:
- CONTRA loss of pain & temp
- IPSI paralysis of CNV, IX, X, XI - Medial medullary syndrome:
- CONTRA spastic paralysis
- IPSI flaccid paralysis of tongue (CN XII)
Organophosphate poisoning
Inhibits cholinesterase in both muscarinic and nicotinic receptors
EXCESSIVE CHOLINERGIC STIMULATION!
“DUMBELS” - muscarinic effects
diarrhea, diaphoresis
urination
miosis
bronchospasm
emesis
lacrimation
salivation
nicotinic effect - muscle fasciulations –> muscle PARALYSIS
ATROPINE reverse muscarinic symptoms - pts. still at risk of muscle paralysis
Pralidoxime - reverses BOTH muscarinic and nicotinic receptors
Von Hippel-Lindau
capillary hemangioblastomas in retina/cerebellum
congenital cysts in kidney, liver, pancreas
increased risk of renal cell carcinoma
NF1
PERIPHERAL nervous system
neurofibromas
optic nerve gliomas
Lisch nodules (pigmented nodules of iris)
caf_ au lait spots (hyperpigmented cutaneous macules)
NF2
bilateral cranial nerve VIII schwannomas
multiple meningiomas
Sturge-Weber syndrome
cutaneous facial angiomas, leptomeningeal angiomas
neurocutaneous disease
ophthalmic (V1) and maxillary (V2) distributions of trigeminal nerve
“tram track” calcifications on skull**
Tuberous Sclerosis
Kidney, liver, pancreatic cysts
cortical and subependymal hamartomas
cutaneous angiofibromas (adenoma sebaceum)
renal angiomyolipomas & cariac rhabdomyomas
Osler-Weber-Rendu syndrome
hereditary hemorrhagic telangiectasia
rupture of telangiectasias - epistaxis, GI bleeding, hematuria
Maple syrup disease: defective breakdown of which branched chain aa
Leucine
Isoleucine
Valine
Accumulation of leucine = neurotoxic
Maple syrup urine disease
Lack branched chain a-ketoacid dehydrogenase: requires several cofactors: “Tender Loving Care For Noone!”
Thiamine pyrophosphate
Lipoate
Coenzyme A
FAD
NAD
Some patients improve on high dose THIAMINE therapy
pyruvate dehydrogenase and a-ketoglutarate dehydrogenase also require same 5 cofactors
Krabbe disease
lack of galactocerebrosidase (no galactocerebroside for myelin)
muscle tone abnormality in infants, developmental delay/regression
Pyridoxine (vitamin B6)
Treats sideroblastic anemia & hyperhomocysteinemia
VIPoma
intractable diarrhea
metabolic ACIDOSIS
HYPOkalemia
HYPOtensive (dehydration and vasodilatory effects of VIP)
VPL
Spinothalamic tract (pain + temperature)
Medial lemniscus (position + proprioception)
Transmit to primary somatosensory cortex
VPM
Trigeminal + gustatory
Transmit to primary sensory cortex
Lateral geniculate
Vision
Optic radiations
Visual cortex (calcarine sulcus)
Medial geniculate
Auditory
Superior olivary nucleus, inferior colliculus (pons)
Temporal lobe
Tuberous sclerosis
a. dominant
Cortical tubers
Subependymal hamartomas (brain) –> seziures/retardation
- bilateral renal angiomyolipoma (blood vessels, smooth muscle, fat)
- Cardiac rhabdomyomas
- Facial angiofibromas
- Leaf-shaped patches (ash leaf patches)
NF1 vs NF2
NF1: a. dominant
optic gliomas
Lisch nodules (pigmented nodules of IRIS)
caf_-au-lait spots
NF2: a. dominant
bilateral acoustic neuromas
meningiomas, gliomas, ependymomas of spinal cord
Von Hippel-Lindau
cerebellar hemangioblastomas
retinal hemangiomas
liver cysts
risk of RENAL CELL carcinoma
Sturge-Weber syndrome
Facial port-wine stain
Leptomengineal capillary-venous malformation
Osler-Weber-Rendu syndrome
Hereditary hemorrhagic telangiectasia - telangictasias of skin + mucosa
recurrent epistaxis
GI bleeding (melena)
Membranoprofliferative glomerulonephritis (MPGN)
Basement membrane splitting
Similar to Alport syndrome:
deafness, ocular manifestations
Focal segmental glomerulosclerosis (FSGS)
IgM* and C3 deposits
Goodpasture’s syndrome
Anti-GBM antibodies react to alpha3-chain of collagen IV
Pulmonary hemorrhages –> hemoptysis (due to damage of alveoli BM)
RPGN
IgG and C3
Crescent formation
RBC casts
Post-streptococcal glomerulonephritis (PSGN)
RBC casts, oliguria
hypercellular glomeruli - “starry sky”
“humps and bumps”
anti-streptolysin O
low C3
periorbital edema, HTN
Wegener’s
Anti-neutrophil cytoplasmic antibodies (c-ANCA)
“necrotizing granulomatous vasculitis”
granulomatosis + polyangiitis
triad:
1) pulmonary symptoms (cough/hemoptysis – focal necrotizing granulomas in lungs)
2) upper respiratory tract (chronic sinusitis, mucosal ulceration of nasopharynx)
3) renal disease – RPGN (crescentic)
Kimmelstiel-Wilson disease
Nodular glomerulosclerosis
Diabetic nephropathy - ESRD
Glomerular hyperfiltration –> increase mesangial matrix/thickening of GBM
K-W nodules
diffuse glomerulosclerosis
hyaline arteriosclerosis
use ACE inhibitors, ARBs - prevent progression of diabetic nephropathy
Presence of petechiae (bleeding disorder)
Platelet dysfunction
CML vs leukemoid reaction
WBC count increase (leukocytosis >50,000)
left shift - immature forms of cells - bands, metamyelocytes, myelocytes, VERY LITTLE -blast cells
differentiate btwn CML and leukemoid reaction:
alkaline phosphatase ELEVATED = leukemoid
alk phosp decrease = CML
Sickle cell anemia patient (infections)
Septicemia (Strep pneumoniae or H. influenza) due to asplenia (more prone to encapsulated organisms)
Osteomyelitis (Salmonella; also S. aureus & E. coli)
Obligate intracellular bacteria
Rickettsia
Legionella
Chlamydia
Stains:
1. Giemsa
2. PAS
3. Ziehl-Neelsen
4. India ink
5. Silver stain
1.Giemsa - Chlamydia, Borrelia, Rickettsiae, Trypanosomes, Plasmodium
2. PAS - Whipple’s disease
3. Ziehl-Neelsen - Acid fast organisms (Mycobacterium)
4. Indian ink - Cryptococcus neoformans
5. Silver stain - Fungi (Pneumocystis), Legionella, H. pylori
Obligate anaerobes
- Clostridium
- Bacteroides
- Actinomyces
Aminoglycosides have no effect on anaerobes.
Encapsulated bacteria
“SHiNE SKiS”
Strep pneumo
H. influenzae type b
Neisseria
E. coli
Salmonella
Klebsiella
group B Strep
Asplenic patients should be vaccinated!
Strep pneumo, H. influenzae, Neisseria.
Catalase-positive bacteria
“CAtaLaSES!”
Listeria
Aspergillus
Candida
E. coli
S. aureus
Serratia
Culture for H. influenzae
Chocolate agar
Factor V (NAD+) and Factor X (hematin)
Culture for Neisseria
VPN media
Vancomycin (Gram +)
Polymixin (Gram -)
Nystatin (fungi)
Culture for lactose fermenting enterics
Pink colonies on MacConkey’s agar
E. coli also on EMB agar (green metallic sheen)
Culture for Legionella
Charcoal yeast extract agar
Pigment-producing bacteria:
1. Actinomyces israelii
2. S. aureus
3. Pseudomonas aeruginosa
4. Serratia marcescens
- Actinomyces - yelllow “sulfur” granules
- S. aureus - yellow
- Pseudomonas - blue-green
- Serratia - red
Protein A
Binds Fc region of Ig
Prevents opsonization & phagocytosis
S. aureus
IgA protease
Cleaves IgA in order for organism to colonize respiratory mucosa
“SHiN”
S. pneumoniae
H. influenza
Neisseria
M protein
Prevents phagocytosis
group A Strep
Rheumatic fever
Mesolimbic-mesocortical pathway
Regulates behavior
Schizophrenia
Nigrostriatal pathway
Coordination of voluntary movements
Parkinsonism
Tuberoinfundibular pathway
Controls prolactin secretion
Hyperprolactinemia
Excessive aldosterone
Na+ retention
HTN
Hypokalemia
Metabolic alkalosis
“Aldosterone escape”
High aldosterone causes increased renal Na+ and H2O absorption –> increase renal blood flow and GFR –> increase rate of sodium excretion from renal tubules
Tumor lysis syndrome
Develops during chemo for cancers w/ rapid cell turnover (poorly differentiated lymphomas and leukemias)
Hyperphosphatemia, Hyperkalemia, Hyperuricemia, HYPOcalcemia
Sarcoidosis
African American
bilateral hilar adenopathy
non-caseating granulomas
Squamous cell lung carcinoma vs. lung adenocarcinoma
Squamous cell: keratin-containing malignant cells; SMOKER
Adenocarcinoma: glandular differentiation w/ atypia; NON-SMOKER
Hodgkin’s lymphoma (common subtype)
Nodular sclerosis subtype
Nodular growth pattern, surrounding fibrous bands, lacunar variant REED-STERNBERG cells
Carcinoid syndrome
RIGHT sided endocardial fibrosis –> pulmonic stenosis/restrictive cardiomyopathy
Skin flushing, abdominal cramping, naseau/vomiting/diarrhea – due to serotonin, kallikrein, bradykinin, histamine, prostaglandins, and/or tachykinins
Test serotonin levels in plasma
Urinary levels of 5-hydroxyindoleacetic acid (serotonin metabolite)
Vanillylmandelic acid
EPI and NE metabolite
Elevated levels of homocysteine
Arterial and venous thrombosis
Development of atherosclerosis
Elevated phenylalanine
phenylalanine hydroxylase deficiency –> CNS damage/mental retardation
PKU
Acute pyelonephritis (bacterial)
E. coli
Klebsiella
Proteus
Enterococci
**all are Gram - rods
Due to vesicoureteral junction issue - urine backflow!
Describe descending path of voluntary muscles
1st order neurons = premotor & motor cortex (frontal lobe - Brodmann’s areas 4 & 6)
Neurons travel through internal capsule –> midbrain –> pons –> PYRAMIDS (medulla)
Fibers decussate @ medulla –> LATERAL CORTICOSPINAL TRACT
(fibers that don’t decussate descend –> ANTERIOR corticospinal tract)
2nd order neurons = anterior horn (fibers synapse)
UMN = lesions above anterior horn
LMN = lesions below anterior horn
UMN symptoms and disease
muscle weakness
increased tone (spasticity)
clasp-knife rigidity
positive Babinski
hyperreflexia, clonus
LMN symptoms and disease
flaccid paralysis
areflexia
atrophy
fasiculations
Poliomyelitis, Werdnig-Hoffman
Tetralogy of Fallot (maneuver to improve cyanosis and dyspnea)
Squatting –> increase systemic vascular resistance
Increase pressure in systemic circulation allows less RIGHT –> LEFT shunting to occur –> more blood in pulmonary circulation to get oxygenated
Vascular defect associated w/ berry aneurysms of Circle of Willis
Coarctation of aorta (due to HTN in branches) leads to:
1) subarachnoid hemorrhage
2) ruptured dissecting aortic aneurysm
3) LV failure
Seen in young adults that die suddenly due to brain hemorrhage
Syringomyelia
upper extremity LMN lesion + loss of P&T
lower extremity UMN lesion
kyphoscoliosis
Superior vena cava syndrome (SVC syndrome)
Small cell lung carcinoma
facial & upper extremity edema
dilated veins of upper torso
Excessive use of ASA
upper GI bleed (loss of gastric cytoprotection)
impaired platelet aggregation
Dermatomyositis
Inflammatory myopathy + cutaneous involvement
Proximal muscle weakness (difficulty climbing stairs, rising from sitting position, combing hair)
+
Gottron papules (flat-topped papules over bony prominences) + heliotrope rash
anti-Jo1 antibodies (specific)
ANA (nonspecific)
elevated CK levels
Macular degeneration
dry MD vs wet MD
Age related (can progress to blindness)
Deposition of fatty tissue (drusen) behind retina (dry MD)
Neovascularization of retina (wet MD)
Patients w/ COPD has chronic hypercapnia (too much CO2 in blood); why should supplemental oxygen be given with caution?
PaO2 is the only respiratory drive stimulator
Too much supplemental oxygen too rapidly –> respiration is inhibited (body thinks there’s already too much O2)
Patients don’t respond to PaCO2 anymore (b/c there’s constant excess of CO2)
Male patients suffering from liver cirrhosis - why is there also gynecomastia?
Hyperestrinism due to:
decreased catabolism of estrogen
+
increased sex hormone-binding globulin (binds testosterone, decrease free testosterone:estrogen ratio)
imbalance –>
gynecomastia, testicular atrophy
decreased body hair
spider angiomata (dilation of superficial capillaries)
Anti-centromere antibodies present
CREST syndrome
Calcinosis - subcutaneous Ca2+ deposits
Raynaud’s
Esophageal dysmotility - fibrosis of distal esophagus
Sclerodactyly - thickening of skin of hands/feet
Telangiectasias
Anti-DNA topoisomerase (Scl-70)
Diffuse scleroderma
Progressive systemic sclerosis –> chronic restrictive interstitial fibrosis
Anti-dsDNA
Malar “butterfly” rash
Anti-histone antibodies (4)
Drug-induced Lupus
Hydralazine
Procainamide
D-penicillamine
Isoniazid
Anti-Ro/SSA
Anti-La/SSB
Sjogren syndrome
keratoconjuctivitis (dry eyes)
xerostomia (dry mouth)
associated w/ increased risk of non-Hodgkin lymphomas
Anti-phospholipid antibodies
Antiphospholipid antibody (also SLE)
Antiphospholipid antibody syndrome:
Hypercoagulable state
Recurrent miscarriages
(paradoxical increase in PTT)
Carpal tunnel syndrome (associated diseases that can cause syndrome)
Compression of median nerve
Pain & paresthesias (pins and needles)
Weakness of thumb abduction and thenar atrophy
Tinel’s sign, Phalen’s sign (tap on flexor surface of wrist)
Associated w/
hypothyroidism (fluid retention)
diabetes mellitus
rheumatoid arthritis
dialysis-associated amyloidosis (deposition of B2-microglobulin)
Overstimulation of a2-adrenergic receptors
Increase release of NE & insulin
Overstimulation of b2-adrenergic receptors
Bronchodilation, vasodilation
Uterine relaxation
Derivatives of pharyngeal arch 1
Trigeminal (CNV)
Derivatives of pharyngeal arch 2
Facial (CNVII)
Derivatives of pharyngeal arch 3
Glossopharyngeal (CNIX)
Common carotid a.
Internal carotid a.
Derivatives of pharyngeal arch 4
Superior laryngeal - Vagus (CNX)
Subclavian aa
Derivatives of pharyngeal arch 6
Recurrent laryngeal - Vagus (CNX)
Pulmonary aa.
Ductus arteriosus
Excessive secretion of Somatomedin C
somatomedin C = insulin-like growth factor-1 (IGF-1)
directly inceased when GH secreted
Results in gigantism in child
unlike excessive estrogen which can cause premature closure of epiphyseal plates in child
Centriacinar emphysema
Upper lung predominant
Associated w/ smoking
Macrophages and neutrophils
Panacinar emphysema
Lower lung lobes
a1-antitrypsin deficiency –> excess neutrophil elastase inside alveoli
Compensatory hyperinflation vs obstructive hyperinflation
Compensatory hyperinflation - compensation for collapsed lobes or surgically removed
Obstructive hyperinflation - fixed or ball valve obstruction (mucus plug, bronchogenic carcinoma) of bronchiles/bronchus
Patient w/ UC history presents w/ fever, diarrhea, signs of shock (decrease BP, increase HR); possibe complication?
Toxic megacolon - cessation of neuromuscular activity –> rapid colon distention –> rupture likely (life threatening perforation)
Diagnosis w/ plain abdominal X-ray
Barium constrast studies & colonoscopy contraindicated (could potentiate rupture)
Lung cancer associated w/ women & nonsmokers
Adenocarcinoma
Lung cancer associated w/ smoking
Small cell carcinoma (central) - associated w/ Cushing syndrome, siADH, Lambert-Eaton syndrome (other neuroendocrine diseases)
Squamous cell carcinoma (necrosis & cavitation, central) - associated w/ hypercalcemia
Muscles responsible for abduction at hip
Gluteus medius
Gluteus minimus
Muscles responsible for adduction at hip
Adductor brevis, longus, magnus
Muscles reponsible for flexion at hip
Iliopsoas
Sartorius
Rectus femoris
Tensor fascia lata
Muscles reposible for extension at hip
Gluteus maximus
Semitendinous
Semimembranous
Biceps femoris (long head)
Muscles important for sitting up from supine position (without hands)
External abdominal obliques
Rectus abdominis
Hip flexors (iliopsoas = psoas major, minor & iliacus)
Cystic hydroma - what is it, what associated disease?
cystic hydroma = neck mass (tumor) apparent at birth in Turner’s syndrome
45XO
Streak ovaries (primary amenorrhea)
Coarctation of aorta
lymphedema (swelling of hands and feet)
Primary amenorrhea; high arched palate, inverted, widely spaced nipples
Turner syndrome
Primary amenorrhea & hirsutism
Polycystic ovarian syndrome
Cri du chat (5p-) syndrome features
round face
cat-like cry
microcephaly
Congenital adrenal hyperplasia - most common cause
21-hydroxylase deficiency
Salt wasting
Ambiguous genitalia (females only)
Testicular feminization syndrome
Androgen insensitivity syndrome
Defect in testosterone receptors
46XY karyotype - appears FEMALE
Blind-ended vaginal pouch
Absence of uterus
Ductus arteriosus
Shunts oxygenated blood from pulmonary artery –> descending aorta (to rest of systemic circulation) – bypasses lungs (since lungs aren’t mature)
Adult remnant of ductus arteriosus
ligamentum arteriosum
Path of oxygentated blood from placenta to fetus
Umbilical vein –> liver –> ductus venosus (bypass hepatic circulation) –> IVC –> right heart –> could go to lungs or go through foramen ovale –> left heart –> systemic circulation
Adult remnant of umbilical vein
ligamentum teres
Origination of umbilical arteries
Fetal internal iliac aa. (carry deoxygenated blood back to placenta)
Allows blood from placenta to bypass hepatic circulation to get to fetal heart
Ductus venosus (in liver)
Blood from umbilical veins go directly to IVC (most O2 content available)
Red pulp vs. White pulp in spleen
Red - filters/destroys old RBCs
White - splenic macrophages present antigens to B and T cells
Spleen - site of extramedullary hematopoiesis
Antibody synthesis
Why are asplenic patients more susceptible to encapsulated organisms?
Splenic opsonizing antibody –> clearance of encapsulated species (S. pneumoniae, H. influenzae, N. meningitidis)
Young female w/ venous thrombosis; PTT time unchanged despite activated protein C administration; why?
Factor V Leiden mutation
Factor Va remains activated –> hypercoagulable state –> abnormal venous thromboses (in young patient w/ no risk factors)
Antiphospholipid antibody syndome
Hypercoagulability
Lupus anticoagulant and/or anticardiolipin antibodies
prolonged aPTT – Lupus anticoagulant most prevalent
Folic acid deficiency (heme related effect)
Hyperhomocysteinemia –> prothrombotic state
Strongest risk factor for cervical intraepithelial neoplasia (CIN)
Multiple sex partners; first intercourse at young age, prostitution
all increase risk of HPV 16 & 18 –> severe cervical dysplasia or carcinoma in situ
Hospitalized patient with recent surgery develops tachypnea, tachycardia, cought, chest pain; cause?
Pulmonary embolism – pulmonary obstruction increase pulmonary resistance –> increases right ventricular afterload (can’t pump out as much to lungs because of increased pressure in lungs) –> right heart failure
Ventilation/perfusion mismatch = appropriate air going into alveoli but obstruction results in less blood supply to all areas of lung –> insufficient gas exchange
Diffusion impairment - hypoxemia; what patients suffer this?
Pulmonary fibrosis
Hyaline membrane disease
A-a gradient in hypoventilation
A-a gradient normal because both arterial and alveolar PO2 are low
Pure RBC aplasia (in setting of normal granulopoiesis & thrombopoiesis)
Marrow falure associated with:
thymoma
lymphocytic leukemias
parvovirus B19 infection
Acute intermittent porphyria
Acute abdominal pain
Peripheral neuropathy
Hyponatremia
Macula densa (location)
junction of ascending loop and distal tubule (regulates GFR)
Conjunctival pallor in fatigued female
Anemia
Level of transferrin in iron deficiency anemia
Liver makes more transferrin (to increase efficiency at “grabbing” any Fe available)
TIBC increase (bc more transferrin is made) - body tries to increase likelihood of attaining as much Fe as possible in Fe depleted conditions (anemia)
Hypersegmened neutrophils + elevated MCV; what deficiencies?
Folic acid or vitamin B12
Delayed afterdepolarizations; causes & complications?
High intracellular Ca2+ or high EPI/NE –> hyperexcitability –> delayed afterdepolarizations
could lead to ventricular tachycardia –> death
Effect of decreased action potential duration
decreased action potential duration –> decreased refractory period –> cell depolarizes more frequently –> a. fib
Acute nausea from systemic chemotherapy - what are of brain is responsible?
Stimulation of chemoreceptor trigger zone in area postrema (dorsal medulla near 4th ventricle)
What important CN and tracts run through the ventral pons?
CN V-VIII
corticospinal tract
medial lemniscus
lateral spinothalamic tract
Inflamatory retinitis in HIV patient w/ CD4+ <50cells/uL; cause and Rx?
CMV
Treat w/ ganciclovir (targets CMV DNA polymerase) to prevent retinal detachment
Platelets aggregate normally in response to ADP, poorly with addition to ristocetin; deficiency?
vWF deficiency
decrease platelet adhesion (since vWF binds gpIb on platelet –> helps attach platelet to subendothelial collagen)
vWF carries factor VIII (impairs an important factor in coagulation pathway)
Results in:
prolonged PTT (coagulation pathway defect)
Increased bleeding time (platelet)
Treatment of vWF deficiency
Desmopressin (DDAVP) –> stimulates vWF release from endothelium
Glanzmann thrombasthenia
deficiency of gpIIb/IIIa –> increased mucocutaneous bleeding
platelet aggregation decreased w/ addition of ADP
Deficiency of thromboxane A2 - possible cause?
ASA treatment - irreversible inactivation of COX in platelets
Congenital deficiency of XII (Hageman); symptoms?
Asymptomatic
Incidental finding bc it causes PTT prolongation
Hyperammonemia effects on brain
Hepatic encephalopathy
depletion of a-ketoglutarate –> inhibition of Krebs cycle
lack of glutaMATE = impaired excitatory neurotransmission
excessive ammonia –> depletes glutaMATE (excitatory neurotransmitter) converted by glutamine synthetase to glutaMINE–> accumulation of glutamine–> astrocyte swelling & dysfunction
Impaired beta-oxidation of fatty acids to acetyl-coA; possible lifestyle?
high alcohol consumption
CARNITINE responsible for transport of FA into mitochondria for beta-oxidation
Lactate level in patient w/ liver cirrhosis?
Elevated lactate (esp. in situations w/ elevated production – sepsis, tissue hypoperfusion)
decreases hepatic lactate disposal –> accumulation of lactate
Idiopathic pulmonary fibrosis causes
Environmental exposure
Sarcoidosis
Collagen vascular diseases
Idiopathic
progressive disease, may require lung transplatition
IPF features
Intersitial fibrosis causes alveoli walls to collapse –> cystic spaces lined by type II pneumocytes
Bronchiolar epithelium (honeycomb fibrosis)
Insidious-onset progressive exterional dyspnea, restrictive pulmonary symptoms, cystic airspace enlargement (honeycomb lung)
Churg-Strauss (pulmonary symptoms)
severe asthma, obstructive features
necrotizing vasculitis
granulomas & infiltration of vessels/perivascular tissue by eosinophils
Goodpasture’s syndome (pulmonary symptoms)
Focal necrosis in alveolar walls & intra0alveolar hemorrhages –> hemoptysis
Characteristics of TOF (4)
Pulmonic stenosis
VSD
RVH
Overriding aorta (straddling VSD)
Why is there varying severities of hypoxemia in patients w/ TOF?
Pulmonic stenosis increases pressure in RV so that it is sometimes equal to LV pressure
Degree of pulmonic stenosis determine whether blood is shunted from L–>R or R–> L
when blood is shunted L–>R, there’s no cyanosis
Painless hematuria (“coca cola urine”) 2-3 days after URI in child/young adult
Deposition of substance found in mesangium
IgA nephropathy (Berger disease)
IgA nephropathy;
purpuric lesions on extensor surfaces (arms, legs, butt);
abdominal pain/vomiting/intestinal bleeding/intussusception
Henoch-Schonlein disease
Differences btwn IgA nephropathy and Post-Strep GN
IgA nephropathy:
develops few days after infection
IgA mesangial deposition
Post-Strep GN:
develops WEEKS after infection
C3 levels low
VIPomas
excess water, Na+, and K+ loss in stool
inhibits gastric acid secretion
watery diarrhea
hypokalemia
achlorhydria
Why are patients w/ Crohn’s more susceptible to gallstones?
Terminal ileum reabsorbs bile acids – in Crohn’s, the terminal ileum most often affected –> no reabsorption of bile
Ratio of cholesterol:bile acid increases –> cholesterol precipitates in bile of the gallbladder as gallstones
Retroperitoneal hematoma from MVA - possible organs involved?
Abdominal aorta, inferior vena cava (rapid blood loss –> hemorrhagic shock)
Pancreas (except tail), kidneys, adrenal glands
parts 2, 3, and portion of 4 of the duodenum
ascending & descending colon, rectum
ureters, bladder
Intraperitoneal structures that can cause hemoperitoneum
transverse colon, liver, spleen
Cardiac defect in Turner’s
Bicuspid aortic valve
early systolic, high frequency click heard over cardiac apex
can progress to aortic stenosis/regurg
Cardiac defect in Down syndrome
ASD
fixed splitting of second heart sound
VSD
holosystolic murmur
Cardiac defect in rheumatic heart disease
mitral stenosis
mid-diastolic, low-pitched rumbling murmur (may begin w/ opening snap)
Cardiac defect in Marfan and Ehlers-Danlos
MVP
Mid-systolic click, late systolic murmur
Cardiac defect in premature infants w/ respiratory distress syndrome
PDA
Trousseau’s sign; what is it an indication of?
Migratory superficial thrombophlebitis – superficial venous thromboses appearing in multiple sites and resolving
Indicates visceral cancer - esp. adenocarcinoma of pancreas, colon, lung
Prinzmetal’s (variant) angina – treatment?
Coronary artery vasospam
Nitroglycerin (or other vasodilators)
Acute transmural myocardial infarction (MI)
peaked T waves (localized hyperkalemia)
ST segment elevation
Q waves
anterior: V1-V3
I, aVL: lateral
Stable angina
Stable atheromatous lesion WITHOUT thrombus
Obstructs greater than 75% of coronary artery lumen
“Bronze diabetes”
Skin hyperpigmentation
Diabetes mellitus
Pigment cirrhosis w/ hepatomegaly
Associated w/ late stage hemochromatosis
Hemochromatosis
High iron GI absorption
Hepatomegaly
Skin hyperpigmentation (sun exposed areas)
Diabetes mellitus (secondary to pancreatic islet destruction)
Arthropathy
Cardiac dysfunction & enlargement
Elevated plasma iron, serum ferritin, >50% transferrin saturation
Wilson’s disease
Pt. younger than 30 yrs. old
Unexplained chronic hepatitis
Low serum ceruloplasmin
Increased urinary copper excretion
Kayser-Fleischer rings
Budd-Chiari syndrome
Thromboti occlusion of hepatic veins and/or the intra/suprahepatic inferior vena cava
Sinusoidal pressure increae –> portal HTN, ascites, hepatomegaly, splenomegaly
Presystolic sound immediately preceding first heart sound - what condition?
S4 gallop is presystolic sound immediately before S1
Best location to hear left vs right sided S4 gallop
Left sided S4 - cardiac apex with pt. in left lateral decubitus position
Right sided S4 - lower left sternal border (tricuspid area) w/ patient in supine position
Why does S4 arise?
Sudden rise in end diastolic ventricular pressure –> atrial contrac against a stiff ventricle (RVH or LVH)
ventricular hypertrophy decreased ventricular compliance –> diastolic dysfunction
What does S1 and S2 represent?
S1 = closing of AV valves
S2 = closing of semilunar valves (pulmonic and aortic)
Cutaneous melanoma gene mutation
Mutated BRAF gene (protein kinase) –> activate signaling pathways –> melanocyte proliferation, metastasis
Substitute a glutamic acid for valine (correct) at position 600
Main risk factor for cutaneous melanoma = UV exposure
Glioblastoma causes overexpression of:
growth factors (PDGF, EGFR, IGF, TGF)
Taste & sensory sensation to anterior 2/3 and poster 1/3 of tongue?
anterior 2/3:
Sensory (pain) - CNV3 (mandibular branch of trigeminal)
Taste - CNVII (facial)
posterior 1/3:
sensory & taste - CNIX
Hydrocele development - cause?
Fluid-filled peritoneal sac within scrotum due to incomplete obliteration of processus vaginalis
processus vaginalis is projection of peritoneal cavity that accompanies descending testis into scrotum
Bright red central papule w/ outwardly radiating vessels that blanch w/ pressure and refill on release; what are they and what are they dependent on?
Spider angiomas
Dependent on estrogen
Soft, blue compressible masses - appears on skin, mucosa, deep tissues, viscera; have dilated vascular spaces with thin-walled endothelial cells; based in dermis – found in brain and viscera - associated with what disease?
Cavernous hemangiomas - associated w/ von Hippel-Lindau disease
Lymphatic cysts lined by thin endothelium - benign tumors present at birth located on neck and lateral chest wall; what disease associations?
Turner syndrome
Down syndrome
Cherry hemangioma vs. Strawberry hemangiomas
Cherry - in adults - increase in number w/ age – proliferation of capiallaries and post-capillary venules in papillary dermis
Strawberry - in children – present in first weeks of life - regress spontaneously by 5-8yrs
Treatment for diabetic ketoacidosis
IV hydration with normal saline & insulin
Insulin decreases lipolysis, decrease production of ketone bodies (increase plasma bicarbonate), decrease K+, decrease glucose, decrease osmolality
Increases sodium and serum bicarbonate
Symptoms of DKA
mental status changes, dehydration, abdominal pain, tachypnea, fruity odor in breath
hyperpnea (Kussmaul respirations) - deep slower breathing to have compensatory respiratory alkalosis (due to metabolic acidosis condition)
increased anion-gap metabolic acidosis
Opioid antagonists uses
treats opioid overdoses –> respiratory acidosis due to hypoventilation
Winter’s formula
PaCO2 = (1.5 x HCO3-) + 8 +- 2
Winter’s formula (when to use it?)
Used to evaluate respiratory compensation when there is metabolic acidosis (diabetic ketoacidosis)
PaCO2 > predicted: concurrent respiratory acidosis
PaCO2 < predicted: concurrent respiratory alkalosis
If PaCO2 persists above range given by Winter’s formula –> patient unable to compensate - has mixed acid-base disturbance consisting of metabolic and respiratory acidoses –> respiratory failure
Elevated AFP
Hepatocellular carcinoma (HCC)
Elevated CEA
Colorectal cancer
Elevated CA-125
Ovarian cancer
other cancers:
endometriosis
lung
breast
pancreatic* cancer
Acid phosphatase elevation
Secondary prostate tumor marker antigen
also in patients w/ active osteoclast-initiated bone resorption
hCG
suspected gestational trophoblastic disease
Physical manifestations of Marfan’s
spinal scoliosis and/or kyphosis
lens dislocation
cystic medial degeneration of aorta –> aortic dissection (cause of death)
defect in glycoprotein fibrillin-1
p53 gene inactivation – 2 hits necessary for malignancy; what is disease w/ inherited mutation in p53 (1 hit already, increasing risk of potentially knocking out both p53)
Li-Fraumeni syndrome
several cancers appear
cancers occur at young age
cancers appear several times throughout lifetime
Follicular lymphoma
Bcl-2 (proto-oncogene) overexpression –> antiapoptosis of tumor cells (immortality)
t(14;18)
CML
Bcr-abl
t(9;22) Philadelphia chromosome
Burkitt’s lymphoma
EBV
C-myc overexpression
t(8;14) – heavy chain on chromosome 14
High mitotic index w/ high cell death rate
Benign macrophages engulf cellular debris –> clear spaces around macrophages = “starry sky appearance”
adolescents and young adults
African form: jaw lesion
Endemic form: pelvis or abdomen involved
Patient hospitalized for acute MI dies 3-7 days after onset of MI; why?
LV free wall rupture (complication)
Occurs when coagulative necrosis + neutrophil infiltration have weaked infarcted myocardium = wall is damaged and more likely to rupture
symptoms: profound hypotension & shortness of breath; jugular venous pressure elevation
LV hypertrophy and prior MI decreases chance of free wall rupture
Most common cause of in-hospital death due to MI
LV failure/cadiogenic shock
Frequent complication of cornary artery fibrinolysis (to get rid of clot)
Systemic bleeding, especially intracranial hemorrhage
Joint pain + cardiac murmur
rheumatic heart disease
antibodies against M-proteins of Streptoccocci
Nasal ulcer + hematuria
Wegeners’s (granulomatosis w/ polyangiitis)
upper resp. tract (sinusitis, nasal ulceration)
lower resp. tract (hemoptysis)
kidneys (RPGN)
c-ANCA
pauci-immune: no anti-GBM antibodies or immune complexes
malar rash + pleural effusion
SLE
circulating immune complex nephritis
dsDNA & anti-Sm
dysphagia & sclerodactyly
CREST syndrome
calcinosis, Raynaud’s, esophageal dysmotility, scerodactyly, telangiectasia
anti-centromere antibodies
Pt. w/ choking spells, dysphagia, coughing; recurrent pneumonia; what could be cause of choking spells?
Cricopharyngeal muscle dysfunction – diminished relaxing of pharyngeal mm. during swallowing –> increased pressure in pharynx eventually causes mucosal to herniate out = Zenker diverticulum (false)
diverticulum palpated as lateral neck mass
food retention in diverticulum –> regurgitation occurs days later –> aspiration pneumonia
Congenital hydrocele
Processus vaginalis remains patent –> fluid from peritoneum accumulates in scrotum
normal development: testis descends through inguinal canal; peritoneal tissue also descend = processus vaginalis
Young black woman; malaise, cough, cutaneous findings (including erythema nodosum - painful shin nodules); bilateral hilar lymphadenopathy; non-caseating granuloma
Sarcoidosis
elevated ACE levels
chronic restrictive granulomatous interstitial lung disease
Cellular immunity
T -cell response (NOT B-cell response)
Vaccines generally stimulate B-cells –> memory B lymphocytes & humor immunity
Wrist drop – radial nerve mononeuropathy; causes?
Compression
Trauma
Diabetic vasculopathy
Vasculitis
Antibodies against neutrophil myeloperoxidase
p-ANCA (perinuclear staining antineutrophil cytoplasmic antibodies)
microscopic polyangiitis or Churg-Strauss vasculitis
Churg-Strauss
idiopathic systemic vasculitis
adult-onset asthma
eosinophilia
mono or polyneuropathy
migratory/transient pulmonary infiltrates
paranasal sinus abnormalities
Mesothelioma
Person works in shipyard - exposure to asbestos
neoplasm of plerua/peritoneum
hemorrhagic pleural effusions & pleural thickening
EM gold standard for diagnosis: numerous long slender microvilli & abundant tonofilaments
Bronchioalveolar carcinoma
type of adenocarcinoma
PERIPHERY of lung (peripheral mass) - pneumonia like consolidation
distribution along alveolar septa
Small cell carcinoma
Major bronchi
hilar mass
Neuroendocrine markers - chromogranin & synaptophysin+
Squamous cell carcinoma
hilar mass
keratinization & intercellular bridges
cavitary lung lesion
Mantle cell lymphoma
t(11;14)
Immunoglobulin heavy chain (IgH) is on 14
cyclin D1 – promoter of G1 to S-phase transition
Mutations of DNA repair enzymes
Breast cancer
Ovarian cancer
Lynch syndrome
Ceroderma pigmentosum
Fanconi anemia
Hemophilia A
X-linked (affects males)
factor VIII deficiency
prolonged PTT
hemorrhage into joints (hemarthrosis); prolonged bleeding after surfical procedures
Hemophilia B
factor IX deficiency
Christmas disease
prolonged PTT
Protein C deficiency
Lack of protein C –> procoagulation
Suffer from recurrent deep venous thromboses
Deficiency in factors II, V, VII, X, & fibrinogen; effect seen in PT or PTT?
PT prolongation
Warfarin – blocks coagulation factors –> also causes PT prolongation
Mucocutaneous bleeding (recurrent epistaxis, gingival hemorrhage); what type of blood disorder?
Defect in platelets –> bleeding time prolongation
also seen in vWF disease and NSAIDs
What does thrombin time measure?
rate of conversion of fibrinogen –> fibrin
thrombin time prolonged when there is deficiency/defective fibrinogen
Low haptoglobin is an indication of?
Hemolytic anemia
Hirschsprung disease
Neural crest cells migrate caudally –> rectum and anus always involved if neural crest cells cease to move in development; sigmoid colon involved 75% of time
Absence of parasympathetic ganglion cells = bowel lumen smaller due to inability to relax
Newborns fail to pass meconium - intestinal obstruction –> bilous vomiting, abdominal distension; tone of anal sphincter usually increased
Pseudogout vs. gout
Pseudogout:
Knee joint
Rhomboid-shaped positive birefringent
Calcium pyrophosphate crystals
Gout:
1st metatarsophalangeal joint
Monosodium urate (salt of uric acid)
Calcific tendonitis
Calcium hydroxyapatitie crystals in periarticular soft tissue (esp. tendons)
Rotator cuff usually affected
Xanthomas
Soft tissue deposits of cholesterol
Hyperlipidemia
Yellow papules on knees, elbows, tendon insertion sites
Reye syndrome
Salicylates given to patients 5-14yrs old.
Hepatic dysfunction – vomiting & hepatomegaly
Microvesicular steatosis
Increased levels of ALT, AST, ammonia, bilirubin, prolonged PT and PTT
Encephalopathy - hyperammonemia –> cerebral edema
The only disease in which ASA is administered to children under 16yrs
Kawasaki disease
Vasculitis of medium-sized arteries (affects children)
Conjunctivitis
Cervical lymphadenopathy
Periungal desquamation (fingers)
Mucocutaneous changes (strawberry tongue)
Centrilobular congestion
Occurs in liver of patients w/ right sided heart failure
Primary biliary cirrhosis
Autoimmune destruction of intrahepatic bile ducts; granulomatous inflammation: infiltration of macrophages, lymphocytes, plasma cells, eosinophils
Cholestasis
Middle aged woman w/ PRURITUS (more severe at night), PALE stool, xanthelasma (suggestive of cholestasis)
Hepatosplenomegaly
Male w/ UC presents w/ fatigue, high alkaline phosphatase
Primary sclerosing cholangitis
Preload
The end volumetric pressure that stretches the right/left ventricle of the heart - initial stretching of cadriomyocytes prior to contraction (related to sarcomere length at end of diastole)
VOLUME in heart after LV filling
Afterload
Tension or stress developed in the wall of left ventricle during ejection (load against which heart has to contract to eject blood) – PRESSURE that heart LV has to pump against and overcome to eject blood
Why is the pO2 in the left atrium lower than in the pulmonary capillaries?
Bronchial arteries return deoxygenated blood (blood that has traveled to supply bronchi and bronchioles) to the pulmonary veins – this results in venous admixture in the pulmonary veins of deoxygenated blood from bronchial arteries & oxygenated blood from the lungs
Determining acid-base disturbance; normal pCO2; normal HCO3-?
pH > 7.45 alkalosis
pH < 7.35 acidosis
pCO2 normal = 40
HCO3- normal = 24
Effect of heroin overdose on blood gases?
Heroin suppresses respiratory centers –> hypoventilation w/ rentention of CO2 (acute phase)
In chronic respiratory acidosis - kidneys compensate by excreting H+ and reabsorbing HCO3-
When does contraction alkalosis occur? Lab findings?
Overuse of diuretics –> volume loss –> increase in aldosterone –> increase rention of Na+ and H2O –> loss of K+ and H+ in kidneys –> loss of H+ causes metabolic alkalosis (contraction alkalosis) bc H+ is traded for HCO3- reabsorption –>
lab findings: high pH, high HCO3-, high pCO2 (CO2 retained to compensate for alkalosis)
Blood gas findings in diabetic ketoacidosis?
low pH, low HCO3- (to neutralize accumulated acidic products) leading to metabolic acidosis, low pCO2 (hyperventilation or Kussmaul breathing to compensate for acidosis)
How does brown fat generate heat?
Have several intracytoplasmic fat droplets
Contain more mitochondria than white adipose
Uncouples oxidative phosphorylation with protein thermogenin
Restrictive cardiomyopathy
reduced LV compliance – diastolic dysfunction –> CHF
restrictive cardiomyopathies = amyloidosis, sarcoidosis, metastatic cancer, products of inborn metabolic errors
contrast with:
dilated cardiomyopathy – systolic dysfunction
viral myocarditis, alcohol toxicity, diphtheritic myocarditis,
doxorubicin (adrianmycin) & daunorubicin – chemo agents also cause dilated cardiomyopathy
Oral thrush - what types of popn. suffer from this infection?
Denture wearers
Diabetics
Immunosuppressed patients (HIV)
Steroid use
Antibiotics, chemotherapy
Luekoplakia
Precancerous lesions w/ white patches that can’t be scraped off
contrast w/ candida infection (oral thrush) – contains white patches that CAN be scraped off
Animal contact – fungal infection
Microsporum species causing dermatophytosis
Varicose veins - causes and complications?
Cause: incompetent venous valves, venous stasis/congestion, edema, increased thrombosis
Complications: painful thromboses, stasis dermatitis, skin ulcerations, poorly healing wounds, superficial infections
NO pulmonary embolism – this is only seen in DEEP venous thromboses (not superficial!)
Cavernous hemangiomas
Soft blue compressible masses
on light microscopy – large dilated vascular spaces
Presence of schistocytes
Microangiopathic hemolytic anemia (TTP, HUS, DIC)
Mechanical damage (prosthetic valve)
HUS vs. TTP; similarities and differences?
Similar symptoms: fever, neurologic manifestations, renal failure, thrombocytopenia, microangiopathic hemolytic anemia
TTP: adults - neurological symptoms predominate
HUS: children - renal involvement predominate
K+ sparing diuretics; location of action?
Spironolactone
Amiloride
Triamterene
K+ sparing diuretics work at collecting duct
Right-sided endocarditis
S. aureus – in IV drug users
Perforations to heart valves, rupture of chordae tendinae, septic emboli to lung
Patient w/ mitral stenosis develops low grade fever & negative blood cultures
Rheumatic fever history left patient with mitral stenosis –> now has another acute case of rheumatic fever
Strep bovis infection; what other conditions is patient most likely suffering from?
Colonic cancer (or other GI malignancy)
Bacteremia
Endocarditis
Culture-negative endocarditis; valvular vegetations present; organisms don’t grown on standard blood culture
HACEK organisms
Haemophilus
Actinobacillus
Cardiobacterium
Eikenella
Kingella
Symptoms of S. aureus caused bacterial endocarditis
Shaking chills (rigors), high fever, dyspnea on exertion, malaise
Right sided endocarditis –> septic embolization into lungs –> pulmonary abscess
Left sided endocarditis –> heart failure, sepsis, septic embolization to brain & end organs
What conditions prevent gallstone formation?
Low cholesterol levels
High bile acid levels
Phosphatidylcholine – allows cholesterol to be more soluble
Obtain cholesterol by 1) absorption & 2) hepatic synthesis of cholesterol via HMG-CoA reductase
How is cholesterol transformed to soluble bile and excreted?
Free cholesterol converted to cholic and chenodeoxycholic acids (bile acids)
Bile acids conjugated –> glycine or taurine –> bile salts –> secreted into bile canaliculi
Phosphatidylcholine makes cholesterol more soluble
Gallbladder hypomotility & more cholesterol –> precipitation of gallstones
Transmural inflammation in Crohns leads to?
Strictures: due to chronic inflammation –> edema & fibrosis –> narrowed lumen (strictures)
Fistulas: inflammation + necrosis –> ulcer formation –> ulcer penetrates entire intestinal wall (transmural) –> formation of fitula
*Ulcerative colitis: damage limited to mucosa and submucosa
Toxic megacolon: complication of Crohn’s, UC, both?
Toxic megacolon affects both Crohn’s and UC; neuromuscular degeneration of intestinal wall –> rapid dilation –> bowel perforation
Worst prognostic factor for patient suffering from alcohol-induced liver damage?
Hypoalbuminemia & prolonged prothrombin time (PT)
both indicate decrease in hepatic function = liver failure
alcoholic steatosis & alcoholic hepatitis (reversible)
alcoholic cirrhosis (irreversible)
cirrhosis = hepatocellular injury + loss of hepatic function
Elevated alkaline phosphatase seen in bone disease; where else in GI/renal disorders?
Biliary disease has elevated alkaline phosphatase
use serum GGT to determine biliary disease (as opposed to bone disease)
Liver fibrinogen synthesis increase/decrease in liver failure?
Liver fibrinogen is coagulation factor and acute phase protein – increase in response to infection/acute inflammation
Liver failure failure = loss of hepatic function to make coagulation factors = LOW liver fibrinogen
Idiopathic membranous nephropathy - what molecular markers is it associated w/?
IgG4 antibodies to phospholipase A2 receptor (found in podocytes)
Minimal change disease; mechanism of pathogenesis?
abnormal T cell production –> glomerular permeability –> fusion of foot processes –> proteinuria
Mixed cryoglobulinemia
IgM deposition in glomerulus –> basement membrane thickening & cellular proliferation
Renal disease caused by multiple myeloma
Deposition of light chains (cast nephropathy)
SLE results in what type of glomerular disease?
Membranous GN
Hypocalcemia: what happens to PTH, Calcitonin, 1,25-dihydrocholecalciferol (active vit D)?
Increase PTH
Decrease calcitonin
Increase 1,25-
Chronic renal disease: what happens to PTH, Calcitonin, 1,25-dihydrocholecalciferol (active vit D)?
“Secondary hyperparathyroidism”
Increase PTH
Increase calcitonin (kidneys can’t excrete calcitonin)
Decrease 1,25-
Hypoparathyroidism: what happens to PTH, Calcitonin, 1,25-dihydrocholecalciferol (active vit D)?
Decrease PTH
Decrease calcitonin
Decrease 1,25-
Administer calcium gluconate: what happens to PTH, Calcitonin, 1,25-dihydrocholecalciferol (active vit D)?
Decrease PTH
Increase calcitonin
Decrease 1,25-
Autosplenectomy
Sickle cell anemia patients
Vaso-occlusive crises –> repeated splenic infarctions –> shrunken, discolored, fibrotic spleen
Brownish discoloration (hemosiderosis) due to extensive sickled RBCs by splenic macrophags (extravascular hemolysis)
Symptoms of sickle cell crises
abdominal pain resolved w/ analgesics + hydration
acute chest syndrome – vaso-occlusive crisis localized to pulmonary vasculature (precipitated by pulmonary infection)
Intrasplenic lipid accumulation
Lysosomal lipid storage disorders (Gaucher’s disease)
Ischemic ATN is most likely a result of damage to which parts of renal tubules?
Proximal tubules
Thick ascending limb of loop of Henle
Ischemic ATN = most common cause of intrinsic renal failure (acure renal failure) in hospitalized pts.
Muddy brown casts seen
Relationship btwn pt. hospitalized after MI and muddy brown casts seen in urine soon after?
Low cardiac output (cardiac arrest) –> ATN –> increased BUN and creatining & oligouria
Proximal tubules & thick ascending limb of loop of Henle most susceptible to ischemia (ATP-consuming activities of ion transport)
Histology of ATN
Flattening of epithelial cells; loss of brush border in proximal tubular cells –> cell necrosis –> denudation of tubular basement membrane
Renal papillary necrosis: disease associations
Diabetes
Analgesic nephropathy
Sickle cell disease
Severe obstructive pyelonephritis
Hemolytic anemia + vasoocclusion in sickle cell anemia; what symptoms do you see w/ hemolytic anemia?
Jaundice - due to unconjugated hyperbilirubinemia (yellow sclera)
Pigmented gallstones
Depressed RBC indices
Painful crises – bone ischemia/necrosis –> Staph & Salmonella osteomyelitis
Autosplenectomy - predisposed to infections w/ encapsulated organisms: which are?
GBS
H. influenzae
S. pneumoniae
M. meningitidis
S. typhi
Splenic sequestration
Young children w/ sickle cell
Vasooclussion –> splenic pooling of RBCs
Medical emergency!!
Marked decrease in Hgb, rapidly enlarging spleen, possible hypovolemic shock
Pt. with sickle cell shows marked macrocytosis; why?
Megaloblastic anemia – impaired DNA syntheis
Lack of folic acid or vitamin B12
Hemolytic anemias predisposed to develop folic acid deficiency b/c of increase RBC turnover (use up all folic acid for DNA synthesis to make new RBCs)
Low folic acid –> impaired DNA synthesis BUT RNA synthesis is not affected –> cytoplasmic contents accumulate (cells swell and get bigger) but can’t divide (bc lack DNA material) –> macrocytosis
Most common hepatobiliary disease in sickle cell patients
Pigmented gallstones
Liver-associated macrocytosis = alcoholic liver disease
26 yr old Caucasian female w/ diplopia - resolves spontaneously; has problems adducting left eye when patient looks right; disease association?
Internuclear ophthalmoplegia (MLF syndrome) – MULTIPLE SCLEROSIS
loss of coordination of lateral conjugate gaze
decreased/blurred vision, central scotoma, monoocular blindness, painful eye movements
Sensory loss, arm/leg weakness, cerebellar symptoms (clumsiness, ataxia) also seen
Pathogenesis of multiple sclerosis
Sclerotic plaques – appear anywhere in the white matter
Plaques form due to demyelination of axons
Changes of white matter seen inside plaques:
Axon demyelination
Depletion of oligodendrocytes (can’t make more myelin)
Accumulation of lipid-laden macrophages (chew up products of myelin breakdown)
Fibrillary astrocytosis (astrocyte proliferation reaction to injury)
Infiltration by lymphocytes & monocytes
Synaptic transmission failure
Myasthenia gravis
Autoantibodies to Ach receptors
Rapidly growing mass in liver of Australian immigrant; mass is damaged during surgery - what is patient at risk for; what is Rx?
Anaphylaxis
Mass is due to Echinococcus granulosus –> forms hydatid cysts
Rupture of cyst contents –> anaphylactic shock
Aspiration of cysts contraindicated.
Larvae implant in capillaries –> inflammatory rxn –> monocytes and eosinophils
Hydatid cyst is encapsulated & calcified; contains flui and budding cells
Rx: surgery, chemo, mebendazole/albendazole
Flat yellow spots on inner surface of aorta; what are these? What can these spots progress to?
Fatty streaks: lipid-filled foam cells that have entered intima through injured, leaky endothelium; foamy appearance due to intracellular lipid-containing phagolysosomes
(foam cells derived from macrophages & smooth muscle cells that have engulfed LDL)
fatty streaks can be seen in aortas of children <1yr old – can progress to form atheromatous plaques, but NOT ALL progress to advanced atherosclerotic plaques
Alternate pathway for blood to return to heart bypassing the IVC
Hemiazygous vein
Azygous vein
Accessory hemiazygous vein
Urease activity test to detect what organism?
H. pylori –> duodenal ulcer
Uses urease to degrade urea into CO2 and NH3
Best detection of congenital heart diseases (VSD, patent foramen ovale)
Echocardiogram
Best detection of bronchiectasis
High resolution chest CT
Patient has hyperacusis; pathology?
Stapedius n. (CNVII) innervates stapedius m. –> paralysis of m. allows wider oscillation of stapes –> increased sensitivity to sound
Prolonged exposure to loud noises causes loss of hearing; how?
Damage to stereociliated hair cells of organ of Corti
Damage to what structures causes conductive hearing loss?
Rupture of tympanic membrane
Defects of middle ear ossicles
Pathway of sound transmission to organ of Corti
Sound –> middle ear via tympanic membrane
Vibration –> oval window via ossicles
Oval window vibration –> basilar membrane vibration –> hair cell cilia bends against tectorial membrane
Hair cells bending –> oscillating hyperpolarization & depolarization of auditory nerve
Carotid sinus baroreceptors & Aortic arch baroreceptors – what innervates them? What occurs once receptors stimulated?
Carotid sinus - Glossopharyngeal n.
Aortic arch - Vagus n.
Stimulation of stretch receptors –> vasodilation, decrease in HR and contractility, decrease in BP
Spoon nails, dysphagia; what deficiency is present?
Iron deficiency anemia
esophageal web = Plummer-Vinson
microcytic hypochromic RBCs
rx: give iron preparation
Deficiency in vitamin B12 or folic acid – what kind of anemia occurs?
Megaloblastic anemia
