Pathology Flashcards
1
Q
PNH
(Proximal Nocturnal Hemoglobinuria)
A
Triad of hemolytic anemia, hypercoagulability, and pancytopenia
acquired mutation in the PIGA gene
associated deficiency of CD55 and CD59 complement inhibitor proteins
PNH results in impaired synthesis of Glycosylphospatidylinositol (GPI), resulting in inability to anchor DAF (CD55) & CD59 to the cell membrane and loss of inhibition of complement-mediated lysis of erythrocytes, leukocytes & platelets.
2
Q
Hyper IgE Syndrome
A
Defective JAK-STAT signaling → impaired Th17
↓ Neutrophil proliferation/chemotaxis
Eczema
Abscesses (ie, cold) (eg, Staphylococcus, Candida)
Recur sinopulmonary infections
Dysmorphic facies (eg, broad nose, prominent forehead)
Retained primary teeth
↑ IgE
Eosinophilia
“ F A T E D “
Facies (dysmorphic), Abcesses(cold), Teeth(retained primary teeth), Eosinophila & inc IgE, Dermatological findings(Eczema).
3
Q
SLE
A
Positive ANA, anti–double-stranded DNA, anti-Smith Antibodies
Skin & Joints:
Malar rash.
Arthritis
Cardiovascular manifestations of SLE:
accelerated atherosclerosis.
verrucous (Libman-Sacks) endocarditis.
Renal involvement in SLE:
(Nephritis or nephrotic Syndrome)
diffuse proliferative glomerulonephritis (characterized by proliferative and necrotizing lesions with crescent formation during active disease).
Light microscopy also classically shows diffuse thickening of the glomerular capillary walls with “wire-loop” structures due to subendothelial immune complex deposition
4
Q
Osteoarthritis
A
Onset >40; increases with age
Knees,Hips,DIP joint1st CMC joint
Morning stiffness None/brief (<30 min)
No systemic Involvement
Hard, bony enlargement of joints
5
Q
Rheumatoid arthritis
A
Onset 40-60; often younger
MCP, PIP, Wrists
Prolonged Morning Stiffness
Systemic Symptoms: Fever, Fatigue, Weight loss
Soft/spongy, warm joints
6
Q
Acute rheumatic fever
A
Endemic in developing countries
Occurs 2-4 weeks after acute group A streptococcal pharyngitis
Molecular mimicry: Anti-streptococcal antibodies attack cardiac & neuronal antigens
Acute/subacute
Migratory arthritis
Pancarditis (mitral regurgitation)
Sydenham chorea
Chronic
Mitral stenosis
Note:
Rupture of Chordae tendonae causes mitral regurge.
“ J ❤️ N E S “
J = Joints (polyarthritis)
❤️ = Myocarditis / MVP
N = Nodes (subcutaneous nodule over bony
prominence)
E = Erythema Marginatum
S = Sydenham Chorea (antibody mediated destruction of corpus straitum of basal ganglia)
7
Q
Acute Kidney Injury
(Pre-Renal)
A
Caused by decr renal perfusion;
BUN/creatinine ratio typically >20:1
Fractional excreti Na+ <1%
Urine osmolality >500 mOsm/kg
Microscopy Hyaline casts
8
Q
Acute Kidney Injury
(Post-Renal)
A
Caused by urinary tract obstruction with normal nephron capacity. Etiologies include bilateral calculi, enlarged prostate, or a renal tumor in an individual with a sole functional kidney.
Bilateral Hydronephrosis is also seen.
9
Q
Acute Kidney Injury
(Intra Renal)
A
Aka Acute Tubular Necrosis
Renal ischemia (eg, hemorrhage, sepsis) or nephrotoxins (eg, aminoglycosides, radiocontrast)
Can also present in setting of cardiac ischemia due likely episode of Hypotension.
BUN/Cr Typically ~10-15
Fractional excretion Na+ >2%
Urine Osm ~300 mOsm/kg
Microscopy Muddy brown casts
10
Q
Auto immune hepatitis
A
Female > male
Associated other autoimmune disorders
Hepatocellular injury (↑ transaminases)
Anti–smooth muscle & Antinuclear Antibodies
Histology: Interface hepatitis (portal & periportal lymphoplasmacytic infiltrate)
11
Q
Primary biliary cholangitis
A
Female»_space; male
Asossiated other autoimmune disorders
↑ alkaline phosphatase , ↑ Bilirubin
Autoimmune destruction of intralobular bile ducts.
Complication includes Cirhosis & Liver failure
Malnutrition
Bile aids in absorbtion of Fat-Sol vitamins thus patient can have Deficiency of Fat sol vitamins( A,D, E &K)
Antimitochondrial & Antinuclear Antibodies
Histology: Florid duct lesion (granulomatous destruction of small bile ducts)
12
Q
Primary sclerosing cholangitis
A
Male > female
Asossiated with IBD (particularly UC)
↑ alkaline phosphatase
± p-ANCA*
Histology: Fibrous obliteration of bile ducts with concentric periductal deposition of connective tissue (onion skin–like pattern )
13
Q
LSD
Fabry Disease
A
XLR Only LSD that is XLR all others are AR
α-Galactosidase A Deficiency Globotriaosylceramide accumulated
Angiokeratomas
Peripheral neuropathy
Glomerulopathy
14
Q
LSD
Tay-sachs
A
AR
β-Hexosaminidase A deficiency
GM2 (ganglioside) accumulation
Macular cherry-red spot (Cherry Red Macula)
Progressive neurodegeneration
15
Q
LSD
Gaucher Disease
A
AR
β-Glucocerebrosidase deficiency
Glucocerebroside accumulation
Hepatosplenomegaly
Pancytopenia
Bone pain/osteopenia
16
Q
LSD
Niemann-Picks disease
A
AR
Sphingomyelinase Def
Sphingomyelin accumulation
Macular cherry-red spot
Progressive neurodegeneration
Hepatosplenomegaly (Not seen in tay-sachs)
17
Q
LSD
Krabbe disease
A
AR
Galactocerebrosidase Def
Galactocerebroside & psychosine accumulation
Progressive neuro degeneration
Peripheral neuropathy
Optic atrophy
18
Q
LSD
Metachromatic leukodystrophy
A
AR
Arylsulfatase A Def
Cerebroside sulfate accumulation
Progressive neurodegeneration
Peripheral neuropathy
19
Q
Reye Syndrome
A
Acute liver failure
Hepatomegaly
Elevated transaminases; coagulopathy
Rapidly progressive encephalopathy
Vomiting, lethargy, seizures, coma following salicylate (aspirin) administration in children.
Aspirin-induced mitochondrial dysfunction causes impaired fatty acid metabolism and microvesicular steatosis of the liver
20
Q
Carcinoid syndrome
A
Diarrhea, Flushing, Wheezing
– Carcinoid Heart Disease (Right sided endcardial fibrosis and thickening of heart valves secondary to exposure to serotonin)
– Vitamin B3 deficiency (Pellagra > Diarhea, Dermatitis, Dementia), Vit-B3 def is because Tryptophan which is also a precursor for Vit-B3 gets shunted more towards production of serotonin therefore Vit-B3 level decrease.
– Elevated 24-hr urinary excretion of 5-HIAA.
– Octreotide for symptomatic patients.
21
Q
Li-Fraumeni syndrome
A
TP53 Mutation
Autosomal dominant
Caused by inactivating mutation in corresponding tumor suppressor gene
Deletion of remaining normal allele (second hit) leads to loss of heterozygosity & malignant transformation
Sarcomas, Breast cancer, Brain tumors, Adrenocortical carcinoma, Leukemia
22
Q
Von Hippel-Lindau syndrome
A
VHL gene mutation (chromosome 3).
- Hemangioblastomas
- Clear cell renal carcinoma
- Pheochromocytoma
23
Q
Familial adenomatous polyposis
A
APC gene mutation
Colorectal cancer
Desmoids & osteomas
Brain tumors
24
Q
Lynch syndrome
A
Autosomal dominant
Inherited DNA mismatch repair defect
MSH2, MLH1, MSH6, PMS2 genes
Colorectal cancer
Endometrial cancer
Ovarian cancer
Patient with postive family history are at risk should start colonscopy by age 5
25
G6PD Deficiency
- Hemolytic anemia due to oxidative stress (infection, sulfa drugs, fava beans)
- X-linked: Asian, African, or Middle Eastern descent
- Pallor & fatigue
- Dark urine, jaundice & icterus
- Abdominal/back pain
↓ hemoglobin, ↓ haptoglobin,
↑ bilirubin & LDH, ↑ reticulocytes
- Bite cells & Heinz bodies
26
Cystic Fibrosis
- Autosomal recessive mutation (∆F508) impairs - - CFTR function
- ATP dependant Chloride channel defective
- Chronic, productive cough
- Recurrent sinopulmonary infections (eg, Staphylococcus aureus, Pseudomonas aeruginosa)
- Pancreatic insufficiency (Def Fat Sol Vitamins)
- Male infertility (bilateral absence of vas deferens)
- Elevated sweat chloride levels
27
Neuroleptic malignant syndrome
Reaction to antipsychotic medications
- Fever (>40 C common)
- Confusion
- Muscle rigidity (generalized)
- Autonomic instability (abnormal vital signs, sweating)
28
Wilsons Disease
AR, Chromosome 13
- Defective Copper transport protien ATP7B.
- Impaired biliary excretion of Copper accumulation of Cu in hepatocytes cause oxidative stress and apoptosis (Cirrhosis).
- Extra hepatic Cu accumulation in basal ganglia (Encephalopathy), Cornea (Kayser-Fischer Ring).
Classical Symptoms Traid:
1-Hepatic (Cirhosis, Liver failure)
2-Neurological (Confusion, Disorientation)
3-Psycological (Depression)
Parkinsonism in young patient is Wilson disease.
Putamen in brain is damaged in wilson disease.
Tx: Penicillamine ( Copper chelator )
29
Hypersenstivity Pneumonitis
Fever , Chills , Cough , Dyspnea
Bilateral interstitial opacities, crackles, restrictive pattern.
bronchial lavage has lymphocytic dominance >20% Often >50%.
30
Absence Seizures
Brief staring spell momentary loss of awareness, abrupt return to full conciousness.
3Hz spike wave of EEG
Rx: Ethuxomide (Inhibit T-type Ca+2 channels in thalamic neurons)
31
AAA
abdominal aortic aneurysm
risk factors
Age>65yrs, Male, Smoking
32
Ménière disease
episodic vertigo, sensorineural hearing loss, and tinnitus with aural fullness.
increased volume and pressure of endolymph in the vestibular apparatus.
33
Pre-Eclampsia & Eclampsia
- Headaches, Vision Changes, Epigastric pain
- New onset HTN(sys>140,dia>90) at or >20wks gestation
- Protienuria and/or signs of end organ damage (i.e renal failure)
Eclampsia: Pre-Eclampsia + Siezure
Tx: Hydralazine
34
Trigeminal Neuralgia
Sudden severe pain in the distribution of CN-V (particularly V1 &V2)
Pain is like stabbing or electric shock
triggered by chewing, brushing, shaving, washing the effected area etc.
Carbamazepine is DOC
35
cardiac tamponade
Becks Triad:
1- Increase JVP
2- Hypotension
3- Muffled heart sounds
36
Hereditary Spherocytosis
RBC membrane defect (Spectrin & Ankyrin), Spherocytes (Increase Osmotic fragility)
1- Hemolytic anemia (dec Hb, Inc LDH)
2- Jaundice
3- Splenomegaly (inc macrophages & congestion)
4- Negative Coombs test
Inc risk of pigmented gallstones & inc risk of aplastic crisis with Parvo virus B-19 infection
37
PSGN
(Post Streptococcal Glomerluonephritis)
Aka Proliferative glomerulonephritis/ Acute glomerulonephritis
After streptococcal inf i.e Strep Pyogenes (2 wks) can present as 1-3 wks of red urine after sore throat.
Periorbital Edema
Hypertension
Micro/Gross Hematuria
Type-3 Hypersenstivity reaction (Antigen-Antibody complex that form in blood and deposit in kidney)
child recovers well, poor prognosis in adults
LM: hypercellular enlarged glomeruli.
IF: Granular deposits of IgG, IgM, C3 on GBM & Mesangium (lumpy-bumpy).
EM: Subepithelial humps b/w podocytes and GBM
Increase Anti-streptolysin-O & Anti-DNase B-titers
Decrease complement protien C3
38
5-Alpha Reductase Def
46,XY genotype
Impaired conversion of testosterone to DHT
Male internal genitalia (eg, testes, vas deferens)
Female external genitalia (eg, blind-ending vagina)
Phenotypically female at birth
Normal male testosterone & estrogen levels
DHT promotes development of male external genetalia and prostate from genital tubercle and urogenital sinus
39
21 Hydroxylase Deficiency
Increased 17-hydroxyprogesterone
Increased testosterone
hypotension, hyponatremia, and hyperkalemia
Low Cortisol and Aldosterone
Low BP
40
17-Alpha hydroxylase deficiency
XY: atypical genitalia, undescended testes
XX: lacks 2° sexual development
the only one that presents with genital virilization in Males
Hypokalemia, Hypernatremia, Hyperglycemia
41
Di-George syndrome/velocardiofacial syndrome
Chromosome 22q11.2 deletion
Defective development of pharyngeal pouches (Defective neural crest migration into derivatives of the third and fourth pharyngeal pouches)
"CATCH-22"
C=Conotruncal cardiac defects (tetralogy of Fallot, truncus arteriosus, interrupted aortic arch)
A=Abnormal facies
T=Thymic hypoplasia/aplasia (T-cell deficiency)
C=Craniofacial deformities (cleft palate)
H=Hypocalcemia/Hypoparathyroidism
22=Chromosome
42
Fragile X Syndrome
CGG Trinucleotide Repeat
Intellectual disability
Prominent Forehead
Large Ears, Long Narrow Face, Prominent Chin
Macroorchidism
MCC of death is Cardiomyopathy.
43
Kartagner Syndrome
Immotile cilia due to AR microtubular defect in dynein arm (dyenin powers intracellular vesicle transport).
Patients present as:
- Infertility
- Situs inversus
- Chronic sinusitis
- Bronchiectisis
44
Horners Syndrome
Ipsilateral
Ptosis, Miosis, Anhydrosis
45
MCA Occlusion
- Contralateral Hemiparesis
- Contralateral Hemisensory loss of face and upper limb, lower limb usually preserved,
- If in dominant hemisphere (usually left) aphasia may also occur.
46
PCA Occlusion
Contralateral Hemianopia with Macular sparing (contralateral supply from MCA)
47
AICA Occlusion
Causes Lateral Pontine Syndrome
Ipsilateral loss of pain or temperature in the face (trigeminal nucleus),
Ipsilateral facial weakness (facial nucleus),
Ipsilateral hearing impairment (cochlear nucleus),
Contralateral loss of pain and temperature in the trunk and extremities (lateral spinothalamic tract),
Cerebellar dysfunction (eg, ataxia, dysmetria).
48
Anterior communicating Artery Aneurysms
compress the central optic chiasm, causing bitemporal hemianopia
49
Posterior communicating Artery Aneurysm
compresses the oculomotor nerve,
Ipsilateral mydriasis, Ptosis,
"down and out" eye deviation
50
ACA Occlusion
Contralateral motor & sensory deficits,
lower limb affected more than upper limb
Bilateral occlusion causes significant behavioral symptoms (eg, abulia), primitive reflexes (eg, Moro, grasp), and urinary incontinence due to damage of the prefrontal cortex.
51
Basilar Artery Occlusion
damages base of pons, contains the corticospinal and corticobulbar tracts, and the paramedian tegmentum.
Patients typically have Quadriplegia, Bulbar dysfunction (eg, facial weakness, dysarthria), and Oculomotor deficits (eg, horizontal gaze palsy).
52
Turner syndrome (45,XO)
Streak ovaries, congenital heart disease, horseshoe kidney,
cystic hygroma, short stature, webbed neck, lymphedema
53
Sarcoidosis
(noncaseating granulomas)
Female with lymphedonopathy
Bilateral hilar adenopathy, uveitis
Hypercalcemia is also seen
Complication:
Granuloma express increased activity of alpha-1 hydroixylase -> increase 1,25 hydroxy vit-D-> ca+2 reabsorbtion in GI lumen, this can cause Nephrolithiasis
54
Paget disease of the breast
Red, itchy, swollen rash of nipple/areola
(sign of underlying neoplasm)
55
Fanconi syndrome
Polyuria, renal tubular acidosis type II, growth retardation, electrolyte imbalances, hypophosphatemic rickets
(multiple combined dysfunction of the PCT)
Impaired PCT reabsorbtion of AA, Glucose, PO4–, HCO3–.
Caused by consumption of expired Tetracyclines.
56
Friedreich ataxia
Autosomal recessive
FXN gene mutation GAA trinucleotide repeat
Staggering gait, frequent falls, nystagmus, hammer toes, diabetes mellitus, hypertrophic cardiomyopathy
MCC of death in patient is Hypertrophic cardiomyopathy
57
Neurofibromatosis type I
- Café-au-lait spots,
- Lisch nodules (iris hamartoma),
- cutaneous neurofibromas,
- pheochromocytomas,
- optic gliomas
58
Neurofibromatosis type II
Bilateral vestibular schwannomas
59
Guillain-Barré syndrome
(acute inflammatory
demyelinating polyneuropathy)
Rapidly progressive limb weakness that ascends following
GI/upper respiratory infection
60
Multiple sclerosis
Nystagmus, intention tremor, scanning speech, bilateral internuclear ophthalmoplegia, optic neuritis
Optic Neuritis: pain with eye movement, intermittently decr vision, swelling of optic disc.
May worsen with heat exposure
Demylinating plaques commonly seen as hyperintense lesion on MRI of brain and spinal cord.
Plaques in the white matter.
Increase IgG in the CSF.
61
Normal pressure hydrocephalus
- Urinary incontinence,
- Gait apraxia,
- Cognitive dysfunction
62
Huntington disease
(autosomal dominant CAG repeat
expansion)
“ C D C “
Chorea, Dementia, Caudate degeneration
Enlargement of Lateral Ventricles is seen in the brain.
63
Parkinson disease
(loss of dopaminergic neurons in
substantia nigra pars compacta)
Resting tremor, rigidity, akinesia, postural instability,
shuffling gait, micrographia
“ T R A P “
T = Tremor
R = Rigidity (Cogwheel rigidity)
A = Akinesia
P = Postural instability
Lewy bodies seen on histology which are made up of Alpha-synuclien.
Depigmentation of substania niagra can be seen on autopsy.
64
Klüver-Bucy syndrome
(bilateral amygdala lesion)
Hyperphagia, hypersexuality, hyperorality
65
Lichen planus
(6 P’s)
Pruritic, purple, polygonal, planar papules and plaques
66
Henoch-Schönlein
purpura
IgA vasculitis (affects skin and kidneys)
Palpable purpura on buttocks/legs,
joint pain,
abdominal pain,
hematuria
Seen in children
67
Kawasaki disease
Spiking Fever for 5 days or more.
Cervical lymphadenopathy, desquamating rash, coronary aneurysms, red conjunctivae and tongue (Strawberry tounge), hand-foot changes
(mucocutaneous lymph node syndrome,
treat with IVIG and aspirin)
68
Reactive arthritis
associated with HLA-B27
Urethritis, conjunctivitis, arthritis in a male
69
Sjögren syndrome
(autoimmune destruction of exocrine glands)
Dry eyes, dry mouth, arthritis
70
Plummer-Vinson syndrome
- Dysphagia (esophageal webs),
- Glossitis,
- Iron deficiency anemia
(may progress to esophageal
squamous cell carcinoma)
71
Whipple disease
(Tropheryma whipplei)
Arthralgias, adenopathy, cardiac and neurological symptoms, diarrhea
72
Acute adrenal insufficiency (adrenal crisis)
Body make too little Aldosterone & Cortisol Shock, altered mental status, vomiting, abdominal pain, weakness, fatigue in patient under glucocorticoid therapy.
73
Addison disease
Chronic 1° adrenal insufficiency
Inc ACTH, Inc MSH, dec Aldosterone & Cortisol
Skin hyperpigmentation, orthostatic hypotension, fatigue, weakness, muscle aches, weight loss, GI disturbances.
74
Sheehan syndrome
(severe postpartum hemorrhage
leading to pituitary infarction)
No lactation postpartum, absent menstruation, cold intolerance
postpartum hemorrhage in pituitary, no LH or FSH = no periods, hyperplasia infarcts; no prolactin = no milk
75
Osler-Weber-Rendu syndrome
Hereditary hemorrhagic telangiectasia
Telangiectasias, recurrent epistaxis, skin discoloration, arteriovenous malformations, GI bleeding, hematuria.
76
Dressler syndrome
Chest pain, pericardial effusion/friction rub, persistent fever following MI
(autoimmune-mediated post-MI fibrinous pericarditis, 2 weeks to several months after acute episode)
77
IgA deficiency
Anaphylaxis following blood transfusion
Recurrent Infections of Mucosal sites (i.e Respiratory, GI) which are protected by IgA.
Patients blood lacks IgA but transfusion product contains IgA which leads to Anaphylaxis when body recogonizes IgA in transfusion product.
78
Leukocyte adhesion deficiency
(type 1; defective LFA-1 integrin)
Late separation (>30 days) of umbilical cord, No pus, Recurrent skin and mucosal bacterial infections.
79
Chronic granulomatous disease
(defect of NADPH oxidase)
Neutrophils lack respiratory burst
Recurrent infections and granulomas with catalase ⊕ organisms
(Staph Aureus, Burkholderia cepacia, serratia marceanes, Nocardia)
Fungi: Aspergillus
Dx: DHR (Dihydrorhodamine test)
NBT (Nitroblue tetrazolium)
80
Hyper-IgE syndrome (Job syndrome)
(neutrophil chemotaxis abnormality)
Recurrent cold (noninflamed) abscesses, eczema, high serum IgE, High eosinophils
“ F A T E D”
F = Facial features (coarse)
A = Abcesses (cold)
T = Teeth (retained primary teeth)
E = Inc IgE, Eosinophilia
D = Dermatological finding (Eczema)
81
Bruton disease
(X-linked agammaglobulinemia)
Male child, recurrent bacterial infections (sepsis, meningitis, skin inf) , no mature B cells, all Immunoglobins are low, paucity of immune structures (i.e tonsils & lymph nodes)
T-cell response normal (normal immune response to viruses)
Present by 6 months of age when maternal antibodies wane off.
82
Alkaptonuria
(homogentisate oxidase deficiency; ochronosis)
Bluish-black connective tissue, ear cartilage, sclerae ( Homogentisic Acid accumulation)
urine turns black on prolonged exposure to air
83
Phenylketonuria
AR : PKU gene mutation
Defective phenylalanine hydroxylase
Phenylalanine can’t be converted to tyrosine
Intellectual disability, Microcephaly, Movement disorders, musty body odor, hypopigmented
skin, eczema.
Increase Tyrosine in diet, restrict phenylalanine in diet.
84
Wernicke encephalopathy
Caused by Vitamin-B1 (Thiamine) deficiency in alcoholics
Confusion, Ophthalmoplegia/Nystagmus, Ataxia (add confabulation/memory loss for Korsakoff syndrome)
Damage to Mamilliary bodies.
85
Cri-du-chat (cry of the cat) syndrome
Microcephaly, high-pitched cry, intellectual disability
86
Edwards syndrome
(trisomy 18)
Miotic Non-disjunction
Infant with microcephaly, rocker-bottom feet, clenched hands, and structural heart defect (VSD)
“ P R I N C E edward “
P = Prominent Occiput
R = Rocker Bottom Feet
I = Intellectual disability
N = Non-disjunction
C = Clenched fist , Cardiac abnormality (VSD)
E = Eighteen Chromosome
87
Patau syndrome
(trisomy 13)
Infant with cleft lip/palate, microcephaly or
holoprosencephaly, polydactyly, cutis aplasia
“ C R A M P “
C = Cleft lip
R = Renal abnormality
A = Abnormal heart
M = Mental retardation, Microcephaly
P = Polydactyly.
88
Duchenne muscular dystrophy
XLR
Mutation in DMD gene encoding Dystrophin, a cytoplasmic protien that plays imp role in anchoring muscle Actin filament to plasma membrane
(Gowers sign)
Child uses arms to stand up from squatting postion,
Weakness of lower limb girdle
Proximal muscle weakness after a period of relatively normal development.
Complication include dilated cardiomyopathy and respiratory insufficiency
Abnormal protien accumulated in cytoplasm.
89
Becker muscular dystrophy
(X-linked non-frameshift deletions in dystrophin; less severe than Duchenne)
Slow, progressive muscle weakness in boys
90
McCune-Albright syndrome
(Gs-protein activating mutation)
Café-au-lait spots (unilateral), polyostotic fibrous dysplasia, precocious puberty, multiple endocrine abnormalities
91
Homocystinuria
AR
Deficinecy of Cystathione Beta Synthase
Vitamin B6 (Pyridoxine) dependant
Accumulation of Homocystiene, Defective conversion of homocystine to Cystiene.
Arachnodactyly, pectus deformity, lens dislocation (downward)
Sometimes respond to Vit-B6 (pyridoxine)
92
Ehlers-Danlos syndrome
(type V collagen defect, type III collagen defect seen in vascular subtype of ED)
Elastic skin, hypermobility of joints, Inc bleeding tendency.
93
Osteogenesis imperfecta
(type I collagen defect)
Blue sclera, multiple fractures, dental problems,
conductive hearing loss
94
Lesch-Nyhan syndrome
(HGPRT deficiency, XLR)
Gout, intellectual disability, self-mutilating behavior in a boy.
“ H G P R T “
H = Hyperurecemia
G = Gout
P = Pissed off (aggressive/ self mutilating)
R = Retardation
T = Tone decreased (Dystonia)
95
Acute lymphoblastic
leukemia/lymphoma (ALL)
- Age < 15 yrs
- Gene mutation on Chromosome21
- Associated with Down syndrome
- t(12;21) better prognosis;
- t(9;22) (Philadelphia chromosome) worse prognosis.
- PBS & Bone marrow have↑ Lymphoblasts
- TdT+, CALLA+
- CD10+
96
Chronic lymphocytic
leukemia (CLL)
- Age > 60 years.
- Most common adult leukemia. CD20+, CD23+, CD5+ B-cell neoplasm.
- CLL = Crushed Little Lymphocytes (smudge cells).
( Crushed/ Crumpled tissue paper like appearence on histology )
97
Hairy cell leukemia
- Adult males.
- Mature B-cell tumor.
- Cells have filamentous, hairlike projections (fuzzy appearing on LM)
- Marrow fibrosis has dry tap on aspiration.
- Pancytopaneia, Massive Splenomegaly
- TRAP+, Assosiated w BRAF mutation
98
Acute myelogenous
leukemia (AML)
- Auer Rods
- Myeloperoxidase ⊕
- APL: t(15;17),
- Responds to all-trans retinoic acid (vitamin A)
- DIC is a common presentation
- Associated with Down syndrome
99
Chronic myelogenous
leukemia (CML)
- Philadelphia chromosome
- (t[9;22], BCR-ABL)
- Myeloid stem cell proliferation
- May transform to AML or ALL (“blast crisis”)
- Responds to BCR-ABL tyrosine kinase inhibitors (eg, imatinib).
- Low Leukocytes ALP.
100
Polycythemia Vera
- Increase in all
- ↑ RBC, ↑ WBC, ↑ Platelets
- JAK2 mutation
- Intense itching after shower (aquagenic pruritus)
- ↓ EPO
101
Essential
Thrombocythemia
- Massive proliferation of megakaryocytes and platelets.
- Bleeding and thrombosis
- ↑ Platelets.
- 1/3 to 1/2 of essential thrombocythemia patients also have JAK-2 mutation.
102
Myelofibrosis
- Atypical megakaryocyte hyperplasia
- Bone marrow fibrosis (Dry Tap)
- Massive splenomegaly
- “Teardrop” RBCs
- ↓ RBCs, Variable WBCs & Platelets.
103
Langerhans cell
histiocytosis
- Presents in a child as lytic bone lesions & skin rash or as recurrent otitis media with a mass involving the mastoid bone
- Express S-100 and CD1a.
- Birbeck granules
(“tennis rackets” or rod shaped on EM)
104
DIC
Dissemninated Intravascular Coagulaopathy
Widespread clotting factor activation
blood oozing from puncture sites
Bleeding complications due to consumption of palelets and clotting factors.
Thrombocytopenia (low platelets)
↑ aPTT , ↑ PT , ↑ INR , ↑ D-Dimers
Decrease Fibrinogen conc
Can be caused by Trauma, Malignancy, Pancreatitis, Toxins, mutliple other causes.
↑ bleeding time, ↑ PT, ↑ aPTT.
↓ Platelet count, ↓ serum fibrinogen, ↑ serum plasmin activity, ↑ serum D-dimer
Blood oozing from puncture site= DIC on USMLE
105
HUS (Hemolytic-uremic syndrome)
In children, Predominately caused by Shiga toxin–producing
Escherichia coli (STEC) infection (serotype O157:H7)
- Thrombocytopenia
- Hemolytic Anemia
- Acute kidney Injury
- Bloody Diarrhea
106
TTP (Thrombotic thrombocytopenic purpura)
In Females,
Inhibition or deficiency of ADAMTS13, Inc platelet adhesion and aggregation
(microthrombi formation)
“ T A A N “
T = Thrombocytopenia
A = Anemia (Hemolytic)
A = Acute kidney Injury
N = Neurological Symptoms
107
Immune thrombocytopenia
Destruction of platelets in spleen.
Anti-GpIIb/IIIa antibodies --> splenic macrophages phagocytose platelets
Inc megakaryocytes on bone marrow biopsy,
decrease platelet count.
↑ Bleeding time, Ⓝ aPTT, Ⓝ PT.
platelets are being consumed so ↑ BT & low platelets but coagulation is normal so Ⓝ aPTT, Ⓝ PT.
Classical case Child after viral infection or women in 30-40s with random bleeding problem
108
Bernard-Soulier
syndrome
Defect in adhesion. decr GpIb --> decr platelet-to-vWF adhesion
Big platelets
109
Glanzmann
thrombasthenia
defect in aggregation. decrease GpIIb/IIIa.
defective platelet plug formation
110
Iron Def Anemia Vs Anemia of Chronic Dx
Anemia of Chronic disease differ from iron deficiency anemia as Iron def has low Ferritin cause the body stores are low, where as in anemia of chronic disease Ferritin levels are high as the body stores are high but iron is bound inside the bone marrow by Hepcidin therefore serum Iron and TIBC are low
111
Lead poisoning
Lead inhibits ferrochelatase and ALA dehydratase
"LEAD"
Lead Lines on gingivae (Burton lines) and on metaphyses of long bones.
Encephalopathy and Erythrocyte basophilic stippling.
Abdominal colic and sideroblastic Anemia.
Drops—wrist and foot drop
112
Severe combined
immunodeficiency (SCID)
adenosine deaminase deficiency
RAG mutation --> VDJ recombination defect
Failure to thrive, chronic diarrhea, thrush
Absence of thymic shadow(CXR), germinal centers
(lymph node biopsy),
113
Wiskott-Aldrich
syndrome
Mutation in WAS gene
"WATER"
Wiskott-Aldrich:
Thrombocytopenia,
Eczema,
Recurrent (pyogenic) infections
Increase IgE, IgA
114
Acute Intermittent Porphyria
Porphobilinogen deaminase def
inc Porphobilinogen
5 P's
Painful Abd, Port-wine colour urine, Polyneuropathy, Psychological disturbance, Precipitated by drugs.
Management of AIP attack include infusion of Hemin which downregulates hepatic ALA-synthase (Rate limitting enzyme in heme synthesis)
CYP450 inducers (Barbiturates, Antiepileptics, EtOH & Smoking) increase activity of hepatic ALA-synthase
115
Porphyria Cutanea Tarda
Uroporphyrinogen decarboxylase deficiency,
Inc Uroporphyrinogen 3
Photosensitivity, Hyperpigmentation
Blisters
Exacerbated by Alcohol
Causes: Familial & Hep-C
116
HELLP Syndrome
Pre-Eclampsia Causing Hepatic Injury
“HELLP”
1- Hemolysis
2- Elevated Liver Enzymes
3- Low Platelets
Schistiocytes are seen on PBS.
117
Polycystic Ovarian Syndrome
increased cysts,
obese, hairy, acne;
no ovulation due to no progesterone;
leads to increased endometrial cancer;
they cannot inhibit LH
118
Amniotic Fluid Emboli
SOB after Delivery
119
Placenta Percerata
Placenta perforates through Serosa
120
Complete Molar Pregnancy
2 sperm + no egg = 46XX; both are paternal; no embryo; looks like a bunch of grapes
121
Abruptio Placenta
Severe pain due to premature seperation of placenta
122
Incomplete Molar Pregnancy
2 sperm + 1 egg = 69 XXY; maternal + paternal; has embryo parts
123
Placenta previa
Placenta completely or partially implanted in lower uterine segment
124
Placenta Accereta
Placenta attached to endometrium
125
Post-partum psychosis
Hallucination, Suicidal, Infanticidal
126
Post-partum depression
Depression after delivery for >2 weeks
127
B-hcg
Blood: 8-10 days after fertilization
Urine: 10-14 days after fertilization
128
Ovarian Hyperstimulation Syndrome
Wt. gain and Enlarged ovaries after clomiphiene use for infertility
129
Adenomyosis
growth of endometrium and myometrium; patients will have an enlarged boggy uterus with cystic areas
130
Ashermans Syndrome
Uteriene scars from multiple D&Cs
131
Endometriosis
painful cyclical heavy menstrual bleeding, powder burns and chocolate cysts due to ectopic endometrial tissue
132
Leiomyoma
Aka Fibroids
Uteriene mass + Heavy menstural bleeding
benign uterus smooth muscle tumors; submucosal types bleed,
subserosal types cause pain
Microscopy show Monoclonal proliferation of myocytes and fibroblasts
133
Epididymitis
Unilateral Scrotal pain decreased by support
MCC chlamydia trachomatis, N.gonorrhea, E.coli
134
Condylomata lata
flat fleshy warts that ulcerate;
sign of secondary syphilis
135
Condyloma accuminata
verrucous "cauliflower" warts, kilocytes;
due to HPV 6 and 11
136
Herpes
Primary: painful grouped vesicles on red base
Secondary: painful solitary lesion
137
Syphillis
Primary: painless chancre, 1-6 weeks
Secondary: rash and condyloma lata, after 6 weeks
Tertiary: neurological and cardiac issues, in bones, after 6 years
138
Toxoplasmosis
Multiple ring enhanced lesions around pareital lobe, from cat feces
139
Congenital CMV
spastic diplegia of legs,
hepatosplenomegaly,
blinding,
Central calcifications
140
Congenital Rubella Syndrome
Classical Triad:
1- Cataracts
2- Sensoneural hearing loss
3- PDA (patent ductus arteriosis)
Blueberry muffin rash on face & spreads to trunk
Can be prevented by giving live attenuated vaccine to mother preconception.
141
Congenital Syphillis
Rhagades (lip fissures),
Saber shins (anterior bowing of the tibia), Hutchinson's razor teeth,
Mulberry molars
142
Hereditary fructose
intolerance
Hereditary deficiency of aldolase B
Fructose-1-phosphate accumulates, inhibition of glycogenolysis and gluconeogenesis
Symptoms present following consumption of fruit, juice, or honey
hypoglycemia, jaundice, cirrhosis, vomiting.
143
Galactokinase
deficiency
Hereditary deficiency of galactokinase.
Galactitol accumulates
galactose appears in blood (galactosemia) and urine (galactosuria); infantile cataracts.
May present as failure to track objects or to develop a social smile.
144
Classic galactosemia
Absence of galactose-1-phosphate uridyltransferase.
accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye)
Symptoms develop when infant begins feeding
failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
145
Lactase deficiency
Insufficient lactase enzyme > dietary lactose intolerance.
Lactase functions on the intestinal brush
border to digest lactose (in milk and milk products) into glucose and galactose.
Bloating, cramps, flatulence (all due to fermentation of lactose by colonic bacteria --> gas), and
osmotic diarrhea (undigested lactose).
146
Hyperammonemia
flapping tremor (asterixis), slurring
of speech, somnolence, vomiting, cerebral
edema, blurring of vision.
CNS toxicity
may involve GABA, α-ketoglutarate, TCA
cycle inhibition, and cerebral edema due to
glutamine-induced osmotic shifts.
147
Ornithine
transcarbamylase
deficiency
XLR
Excess carbamoyl phosphate is converted
to orotic acid (part of the pyrimidine synthesis pathway).
Inc orotic acid in blood and urine, Dec BUN, symptoms of hyperammonemia.
No megaloblastic anemia (vs orotic aciduria).
148
Maple syrup urine
disease
Blocked degradation of branched amino acids
(Isoleucine, leucine, valine) due to Decrse branched-chain α-ketoacid dehydrogenase (B1).
vomiting, poor feeding, urine
smells like maple syrup/burnt sugar, progressive neurological decline
149
Cystinuria
Hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine (COLA).
Excess cystine in the urine can lead to recurrent
precipitation of hexagonal cystine stones.
150
GSD
Von Gierke disease
(type I)
Glucose-6-phosphatase Deficiency
Severe fasting hypoglycemia,
Incrse Glycogen in liver and
kidneys, Incrse triglycerides, Incrse Uric Acid.
Gout, Hepatomegaly,
Renomegaly.
Von-Gierke= 3 G
Glycogen in liver, G6P, Gout
Impaired gluconeogenesis and
glycogenolysis.
151
GSD
Pompe disease
(type II)
Lysosomal acid α-1,4-
glucosidase (acid maltase) Deficiency
Cardiomegaly, Hypotonia, Enlarged tongue.
152
GSD
Cori disease
(type III)
Debranching enzymes
(α-1,6-glucosidase and
4-α-d-glucanotransferase) Deficiency.
Similar to von Gierke disease,
Gluconeogenesis is intact.
153
GSD
Andersen disease
(type IV)
Branching enzyme Deficiency.
hepatosplenomegaly
and failure to thrive in early
infancy.
154
GSD
McArdle disease
(type V)
Skeletal muscle glycogen
phosphorylase
(myophosphorylase) deficiency,
Incrse glycogen in muscle
painful muscle cramps,
myoglobinuria (red urine), Weakness & fatigue w exercise
no rise in lactate levels after exercise
155
LSD Mucopolysaccharidosis
Hurler syndrome
AR
α-l-iduronidase deficiency.
Heparan sulfate, dermatan sulfate accumulation
Developmental delay, skeletal
abnormalities, airway obstruction,
corneal clouding, hepatosplenomegaly
156
LSD Mucopolysaccharidosis
Hunter Syndrome
XLR
Iduronate-2 (two)-
sulfatase deficiency.
Heparan sulfate, dermatan sulfate accumulation.
Mild Hurler + aggressive behavior, no corneal clouding.
"Hunters see clearly (no corneal clouding) and aggressively aim for the X (X-linked recessive)"
157
Metabolic Fuel Breakdown
1g carb/protein = 4 kcal
1g alcohol = 7 kcal
1g fatty acid = 9 kcal
158
Diabetic Mononeuropathy
Hx of Diabetes
Microvascular damage to tissues (i.e Nerves)
Can cause Abducens nerve palsy present as
Esotropia
Unilateral adduction deficit
Diplopia in horizontal gaze
159
Waterhouse-Fredriechsen Syndrome
Is caused by gram –ive diplococcus
Niesseria Meningitis
Meningitis, Sepsis, DIC, Bilateral adrenal hemorrhage.
Adrenal insufficiency presents as:
Hypotension, Hyperkalemia, Hyponatremia and Hypoglycemia due to deficiency of aldosterone and glucocorticoids.
160
LSD
I-cell disease
Aka inclusion disease
N-acetyl glucosamine 1 phosphate
Sphingolipid and mucoploysachride accumulation in lysosomes
Corneal clouding
Failure to thrive
161
Hyperlipidemias
Familial Chlyomicronemia (type-1)
Lipoprotien lipase defect
Increase Chylomicrons
P/E
Acute pancreatitis
Lipemia retinalis
Erouptive xanthomas
162
Hyperlipidemias
Familial Hypercholestrolemia (type-2)
LDL receptor defect
Increase LDL
P/E
Tendon xanthomas
Xanthelesmas
Premature atherosclerosis
163
Hyperlipidemias
Familal dysbetalipidemia (type-3)
Apo E defect
Increase Chylomicrons & VLDL
P/E
Premature atherosclerosis
Xanthomas
164
Hyperlipidemias
Familial Hypertriglycerdiemia (type-4)
Polygenic
Increase VLDL
P/E
Coronary artery disease
Pancreatitis
Diabetes mellitis
165
Acute Graft Vs Host Disease
Damage to the Host cells (i.e Body)
Common following stem cell transplantation
Fever , Rash (maculopapular rash), Diarrhea and Tranaminitis.
Result of HLA mismatch
Donor T-Lymphocyte response against host cells
Involves Apoptosis
In comparison Host vs Graft Disease
Damage is by the body to the graft (i.e transplanted organ)
166
ADPKD
( Autosomal dominant polycystic kidney disease )
Genetic mutation in polycystin ( PKD1 , PKD2 )
Multiple large cysts in kidneys due to structural abnormalities in renal tubules.
Inherited with complete penetrance & Variable expressivity.
Can present with:
Flank pain, Hematuria, HTN, Progressive CKD.
167
Bells Palsy
Isolated facial nerve palsy (CN-VII)
Typically secondary to HSV reactivation
Complete ipsilateral facial weakness involving forehead,
1- Loss of forehead or brow movements.
2- Inability to close eyes & drooping of eyelids.
3- Loss of nasolablial folds & drooping lower lip
Taste and hearing abnormalities, (Loss of taste ant 2/3 of tounge & Hyperacusis)
Decreased tear production
Loss of sensation from portions of pinna to EAC
168
Occulomotor Nerve Palsy
Occulomotor nerve innervates motor innervation to levator palpebrae superioris, Superior, Medial, Inferior rectus muscle and inferior oblique muscle
Deficit presents as:
Ptosis, Exotropia, Hypotropia
169
Abducens Nerve Palsy
Abducens Nerve exits brainstem ventrally to pontomedullary junction.
Innervates the lateral rectus muscle of eye
May result from microvascular ischemia
Presents as;
Binocular horizontal diplopia
Ipsilateral abduction deficit of effected eye.
170
Myotonic Dystrophy
Expansion of Trinucleotide repeat CTG
Type-1 : DMPK gene
Type-2 : CNBP gene
Characterized by:
Ptosis, Facial muscle atropy, Muscles weakness, Myotonia, Cataracts, Frontal balding, Cardiac arythmias, Hypogonadism.
More frequently affected muscles are facial muscles, sternlcloidomastoid, distal forearm, instrinsic hand and ankle dorsiflexion.
It is assosiated with presence of ring fibers and central nuclei on muscle biopsy.
171
Mitochondrial Myopathy
Group of disorders characterized by
Neurological and Muscular symptoms.
Mutation in mitochondrial enzyme involved in oxidative phosporylation and mitochondrial function.
Mitochondrial inheritance.
Muscle biopsy show Ragged Red Fibers.
172
Insulinoma
Tumor of pancreatic islet cells (Beta-cell tumor)
Hypoglycemia
High Insulin, High C-peptide
Whipples traid:
– Hypoglycemia.
– Mental symptoms induced by fasting or exercise.
– Symptoms relieved by IV glucose.
173
Glucagonoma
Rare pancreatic tumor (Alpha cell tumor)
Increase HbA1c , Increase Insulin , Increase Glucagon.
Wt.loss , Depression , Necrolytic Rash
— New onset of Diabetes (Hyperglycemia) with Necrolytic migratory erythema >> Glucagonoma.
174
Vipoma
Rare tumor assosiated with Multiple Endocrine Neoplasia (MEN)
Also termed as WDHA syndrome
Watery Diarrhea, Hypokalemia, Achlorhydria (absence of hcl in gastric secretions)
Hyperglycemia (fasting state sensed by body)
Hypercalcemia
175
Dermatomyositis
Presents with Cutaneous and Musculoskeletal manifestation
Heliotrope rash (pink or light purple rash over upper eyelid), pink papules over dorsal fingers (Gottron papule), Piokilodermatous rash in shawal distribution (pink to iliac colouref patches with talengectaseias over upper back and sun exposed chest)
Proximal muscle and extremity weakness (i.e difficulty lifting arms over head for example to comb the hairs)
Cancers like Adenocarcinoma of ovaries is assosiated with Dermatomyositis as paraneoplastic syndrome.
Anti-nuclear antibody, Anti-Jo antibody, Anti-SRP, Anti-Mi-2 antibodies.
176
Anticholinestrase poisoning
Aka Organophosphate poisoning
Irreversible inhibition of acetylcholinesterase
Symptoms include:
Vomitting, Diarrhea, Diaphoresis, Urination, Lacrimation, Salivation, Bronchorrea, Bronchospasm, Bradycardia, Siezures, Muscle weakness
Responsible toxins are:
Parathoin , Fenthoin , Malathoin.
Tx:
Atropine : antagonizes muscranic receptors.
Pralidoxime : Regenerate function AchE.
177
Granulomatous with Polyangitis (GPA)
Systemic necrotizing granulomatous vasculitis affected small and medium vessels.
Assosiated with c-ANCA (cytoplasmic anti neutrophil cytoplasmic antibody).
GPA most commonly infects Sinopulmonary tract, Kidneys and Skin.
Can present as:
Sinusitis, Otitis Media, Mastoditis, Nasal ulceration w Epitaxis, Hemoptysis, Cough.
Hematuria increase risk of RPGN and Renal failure.
Fever, Wt.loss and fatigue are constitutional symptoms.
178
Acute Pancreatitis
Epigastric abdominal pain radiates to back
Nausea
Vomitting
Grey turner sign (bruising of flanks)
Cullen sign (bruising of umbilicus)
↑ Amylase , ↑↑ Lipase ( 3 times normal )
Hypocalcemia
As fat is autodigested by pancreatic enzymes Saponification occurs (hydrolyses of ester from alchol and carboxylase salt i.e triglycerides or phospholipids containing ester linkage are hydrolysed catalysed by pancreatic lipase, Ca+2 often complexes with these products causing hypocalcemia)
Pt often has hx of gallstones, alcohol use disorder, trauma, hypertriglyceridemia, hypercalcemia.
179
Hyper Parathyroidism
Presents as:
Hypercalcemia, Recurrent Nephrolithiasis, Bone pain from osseous resorption, Polyuria, Constipation, Psychiatric disturbance.
MCC parathyroid chief cell adenoma
Incr PTH , Incr Ca+2 , decr PO4-
180
Zollinger-Elison Syndrome
(ZES)
Traid of:
Pancreatic/Duodenal tumor (Gastrinoma)
Increase Gastric secretion (Non responsive to antiacids)
Peptic Ulcer (Distal Duodenal Ulcer)
Other symptoms
Diarrhea
Abdominal pain
Malabsorbtion
Post-prandial pain
Gastrin increases in response to exogenus Secretin (normally secretin inhibits gastrin production in ZES effect is opposite)
181
Multiple Myeloma
Most common primary bone tumor in elderly
Over productio of IgG (55% cases) > IgA.
M-spike with IgG on electrophoresis.
“ C R A B “
C = hyperCalcemia
R = Renal Involvement , Reaulux formation
A = Anemia
B = Bone lesions/ Back pain (lytic lesions, punched out lesions on x-ray)
Rouleaux formation RBC stacked like poker chips
↑ ESR
Urinanalysis show Ig light chains
( Bence-jones protienuira ), —ive urine dipstick
Complications:
↑ risk of infections,
1° Amyloidosis
Multiple Myeloma is tumor of plasma cells.
182
Waldenstorm Macroglobulenemia
Overproduction of IgM
M-spike with IgM
Peripheral Neuropathy
No CRAB findings
HYPER VISCOSITY SYNDROME:
Headache
Blurry vision
Raynaud phenomenon
Retinal hemorrhages
Complications: Thrombosis
183
Monoclonal Gammaopathy of Undetermined Significance
( M G U S )
Over production of any type of Immunoglobin
Usually Asymptomatic
1-2% per year risk of transitioning to Multiple Myeloma
184
Myelodysplastic Syndrome
Seen in older adults.
Stem cell disorder –> ineffective hematopoesis
Defect in maturation of non-lymphoid lineage
Bone marrow blast <20% ( Vs AML blast> 20%)
Risk factors: radiation, chemo, benzene
Risk of transformation into AML
Neutrophils with Bilobed Nucleus.
185
Tumor Lysis Syndrome
Seen in leukemias/lymphomas, usually caused by treatment initiation
Muscle weakness
Arythmias (incrse K+)
Siezures (decr Ca+2)
Acute Kidney Injury (incrse PO4– , incr Uric acid)
186
Serotonin Syndrome
– Neuromuscluar hyperactivity (clonus,hypereflexia, hypertonia, tremors, siezures)
– Autonomic stimulation
(hyperthermia, diaphoresis, diarrhea)
– Agitation
Treatment:
Benzodiazipine (to calm the patient)
Cyproheptadine (serotonin recptor antagonist)
Note: Differentiation point b/w serotonin syndrome and NMS is that only serotonin syndrome has Clonus & Hyperreflexia, NMS has Hyporeflexia and no clonus
187
Neuroleptic Malignant Syndrome
Feared side effect of typical antipsychotics
Progression to EPS
Muscle rigidity, Myoglobinuria
Fever
Enchephalopathy
Unstable vitals
Elevated Liver enzymes
188
Metabolic Syndrome
Wt.gain , Diabetes , Hyperlipidemia
Atypical antipsychotics have highest risk of causing metabolic syndrome (i.e clozapine, olanzipine, quetiapine)
189
Tourrette syndrome
Motor and vocal tics that presist for > 1 year.
Tx: Fluphenazine, Resperidone
190
Alcohol Intoxication
Slurred speech, Mood changes, Horizontal Nystagmus, Lack of coordinated movement.
Delerium tremens: life threatnening alcohol withdrawal symptoms peak 2-4 days after last drink, characterized by autonomic hyperactivity
( Tremors, Anxiety, Siezures, Electrolyte disturbances, Respiratory alkalosis)
Drugs for withdrawal: benzodiazipines (lorazipam, diazepam)
Tx for alcoholism:
Disulfram (to condition the patient to abstain from alcohol use)
Acamprosate, Naltrexone (reduce cravings)
Support group.
191
Opiod Intoxication
Sx of OD:
Euphoria,
Respiratory/CNS depression,
Pupillary constriction (pinpoint pupils)
Tx: Naloxone (Opiod recptor anatgonist)
Sx of Withdrawal:
Flu-like symptoms Sweating
Dilated pupils
Piloerection
Fever, Rhinorhea, Lacrimation
Nauseas, Stomach cramps, Diarrhea
Tx: Naltrexone
192
Cocaine Intoxication
Cocaine blocks Dopamine, Serotonin, NorEpi reuptake.
Sx of intoxication:
Pupillary dilation
Hallucinations (including tactile i.e feeling bugs all over the body aka cocaine crawlies)
Paranoid ideations
Angina, SCD
Perforation of nasal septum
Tx: Alpha blockers (Phenoxybenzamine, Phentolamine) , Benzodiazipines, B-blockers C/I.
193
MDMA intoxication
Aka Ecstacy
Club drug
For social closeness
Distorted sensory and time preception
Teeth clenching
Life threatening effects include:
Tachycardia, HTN, Hyperthermia, Hyponatremia, Serotonin syndrome
194
Marijuana/ Cannaboid intoxication
Euphoria , Anxiety , Paranoid delusions , Preception of slowed time , Impaired judgement , Social withdrawal , Increase Appetite , Dry mouth , conjunctival injection , Hallucination
195
Phenycyclidine / PCP intoxication
Violence , Impulsivity , Psychomotor agitation , Nystagmus , Tachycardia , HTN , Analgesia , Psychosis , Delerium , Siezures
196
LSD intoxication
Action at serotonin receptor
Visual hallucinations
Synesthesia ( seeing sounds as colours )
Pupillary dilation
Paranoia
Psychosis
Possible Flashbacks
197
Inhalant Abuse
Young adult, Teenager
Rapid onset of Bilegerence , Assaultiveness
Apathy , Impaired judgement , Blurred vision ,
Coma.
Resolution can be just as rapid
198
Rett Syndrome
Only in girls
Decreased head growth
Hand wringing
Lose motor skills (Normal until 5 months of age)
199
Autism
Poor eye contact , Repetitive movements, lack verbal skills and bonding, symptoms since birth
200
Major depressive disorder
( M D D )
Need 5 of 8 SIGECAPS for over 2 weeks
“ S I G E C A P S “
S = Sleep disturbances
I = Interest/ Lipido loss
G = Gulit
E = Energy loss
C = Concentration loss
A = Appitite loss
P = Psychomotor agitation
S = Suicidal Ideation (hopelessness)
201
PSGN
most common in kids;
sub epithelial humps - IgG, C3, and C4 deposition;
lumpy bumpy on EM;
ASO antibodies
202
Membranous Proliferative Glomerulonephritis
tram-tracks on LM, basement splitting
203
Urge Incontinence
urgency leads to complete voiding,
detrusor spasticity leads to small bladder volume;
PVRV: 5-10mL
204
RTA Type-2
Inability of PCT to reabsorb bi-carb (HCO3–).
proximal RTA = bad carbonic anhydrase, lost all bicarb in urine
205
Focal Segmental Glomerulonephritis
Seen in
IV drug abusers, African Americans, Hispanics, and HIV patients
206
Overflow Incontinence
cannot completely empty bladder
PVRV: residual volume > 100ml
207
Minimal Change Disease
Most common nephrotic syndrome in kids
fused foot processes on EM, no renal failure, loss of charge barrier
208
Membranous Glomerulonephritis
Most common nephrotic syndrome in adults
LM: BM spikes,
EM: sub epithelial spikes and domes
IF: granular/ linear
209
Stress Incontinence
weak pelvic floor muscles
urinating when coughing, laughing, etc.
estrogen effect;
PVRV = 50ml
210
Central Pontine Demyleinosis
this happens when you correct serum sodium faster than 0.5mEq/hr, causing the pons to infarct, leaving the patient in a coma where they can only blink
211
RTA Type-1
Inability of DCT to secrete Proton (H+).
distal (DCT) RTA = H+/K+ exchange in collecting duct is broken,
high urine pH (low H+ in urine)
212
Diseases with increase anion gap metabolic acidosis
MUDPILES:
- Methanol,
- Uremia,
- DKA,
- Paraldehyde, Phenformin,
- INH, Iron tablets,
- Lactic acidosis,
- Ethylene glycol,
- Salicylates
213
Barter Syndrome
@ ascending loop
JG cell hyperplasia with renin excess;
no increase in blood pressure;
defect in kidney's ability to reabsorb potassium
--presents like chronic loop diuretic use--
214
Carney Complex
Classically Traid of:
- Cardiac Myxoma
- Perioral Melanosis
(fancy way of saying hyperpigmentation)
- Endocrine Hypersecretion
(classically bilateral pigmented zona fasiculata hyperplasia resulting in Cushing syndrome, but can also be Hyperthyroidism or Growth Harmone)
215
Holosystolic Murmurs AKA Pansystolic Murmurs
1- Mitral regurgitation (mitral insufficiency; MR)
2- Tricuspid regurgitation (tricuspid insufficiency; TR);
3- Ventricular septal defect (VSD).
216
Mid-Systolic Murmurs
(Crescendo-Decrescendo Systolic)
1- Aortic stenosis (AS)
2- Hypertrophic obstructive cardiomyopathy (HOCM)
3- Pulmonic stenosis (PS)
217
Diastolic Opening Snap Murmur
Mitral stenosis (MS) à has diastolic opening snap,
followed by a mid-late decrescendo diastolic murmur
218
Mid-Systolic click Murmur
MVP (Mitral valve prolapse)
219
Continuous Machine Like Murmur
PDA
Aka Pansystolic - Pandiastolic
Also described as to and fro murmur.
220
Murmur with Fixed S2 Splitting
ASD (Atrial Septal Defect)
221
Holo-diastolic / Pan-diastolic Murmur
1- Aortic regurgitation (aortic insufficiency; AR)
2- Pulmonic regurgitation (pulmonic insufficiency; PR)
222
Pan-diastolic and loudest in early-diastole
Classically AR (decrescendo
holo-diastolic murmur)
223
Principle regarding heart murmurs
All will get worse / more prominent with more volume in the heart, however,
MVP and HOCM are the odd ones out; they’ll get worse with less volume in the heart.
224
Kid with SCD, Fever, Tachycardia presents with a Murmur
Transient, functional high-flow murmur secondary to tachycardia à murmur will subside once HR returns to baseline.
No cardiac abnormality involved.
225
Aortic Stenosis
Mid-systolic (crescendo-decrescendo systolic)
murmur classically at 2nd intercostal space, right sternal border, with radiation to the carotids;
classically presents as: " S A D "
Syncope , Angina , Dyspnea.
Has slow-rising pulse (“pulsus parvus et tardus”)
Usually causes Concentric Hypertrophy due to pressure overload.
can be seen with normal aging or bicuspid aortic valve.
226
Maneuvers that decrease blood in the heart
Valsalva; standing up from seated position; sitting up from supine position;
administration of nitrates any of these will cause MVP + HOCM to get worse;
all other murmurs will soften or not change.
227
Maneuvers that increase blood in the heart
Lying down; leg raise while supine; squatting; handgrip
228
Gilbert Syndrome
Isolated indirect Hyperbilirubinemia
Recurrent episodes of self resolving jaundice
Brought on Stress, Mensturation, Fasting, Exercise, Surgery etc
Bilirubin storage and excretion is normal, conjugation is decreased & decr UDP glucoronyl transferase activity.
AST , ALT are normal
229
Malignant Hyperthermia
Widespread muscle rigidity after administration of inhalation anesthetics and/or succinylcholine to genetically susceptible individuals.
Genetic mutation in Rayanodine receptors
Unregulated sarcoplasmic Ca+2 release —> sustained muscle contraction
Symptoms:
- Masseter muscle spasm
- Widespread muscle rigidity
- Hypercarbia
- Rhabdomyolysis —> Hyperkalemia & ARF.
- Hyperthermia (late manifestation)
Dantrolene is used for treatment it directly inhibits intracellular Ca+2 release from abnormal ryanodine receptors (RYR1).
230
Hartnup Disease
AR
Inactivating mutation effecting transport of neutral amino acids. Particularly Tryptophan which is a precursor for Niacin, Serotonin & Melatonin.
Present with pllegra like skin erouptions (Rash following sun exposure)
Cerebellar Ataxia
Niacin Deficiency
Neutral Aminoaciduria (Alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine & tryphtophan)
231
Reactive Arthritis
Traid of:
- Uretheritis
- Conjunctivitis
- Mono/oligo articulaticular arthritis
Assosiated with HLA-B27 & Sacroilitis
232
Obssesive Compulsive Disorder (OCD)
Presistant intrusive thoughts leading to repetitive, ritualistic behaviours.
Tx: SSRI are 1st line for OCD
Block the reuptake of serotonin into presynaptic neurons, increase availability of synaptic sertonin & subsequent cascade of downstream neurobiological effects.
233
Zenkers Diverticulum
False Diverticulum
Develops immideately above UES
Posterior mucosal herniation between fibers of Circophyrngeus muscle
Pathophysiology : (diminished relaxtion of circopharengeal muscle during swallowing leads to incr intraluminal pressure eventually causing mucosa to herniate through a zone of muscle weakness in posterior hypopharynx)
Presents as:
- Dysphagia
- Regurgitation/ Halitosis
- Aspiration
234
Meckels Diverticulum
True diverticulum
all 3 layer: mucosa, submucosa, muscularis
Outpouching from ileum w fibrous band connected to umbilicus
Congenital anamoly due to incomplete obliteration of Vitelline (omphalomesenteric) duct
Classically present with painless hematochezia +/– Iron def anemia.
Abdominal pain if inflamed (i.e Diverticulitis)
Often contain Heterotrophic gastric mucosa secreting HCl and causing local ulceration & bleeding of small bowel.
Rule of 2: Present by age 2, <2 inches long, Located with 2 feet of Ileocecal valve
Complications: Intussuception, Volvulus, Bowel Perforation
235
11-Hydroxylase Deficiency
Incr 17-OH-progesterone , Incr DHEA-S ,
Incr Androstendione,
Increase BP
Cortisol and Aldosterone are low but their precursors are high and have some effect
236
Scleroderma/ Systemic Sclerosis
It can be localized called as localized scleroderma or diffuse/systemic scleroderma called as systemic sclerosis.
AKA “ C R E S T syndrome ”
C = Calcinosis (Ca+2 deposit in skin)
R = Raynauds Phenomenon
E = Esophageal dysfunction(acid reflux,↓motility)
S = Sclarodactyly (thickening & tightening of
skin on fingers & hands)
T = Telangectasias
– Anti-Centromere Antibodies are classic for CREST syndrome.
– Anti-Topoisomerase (Anti-Scl-70) are seen in diffuse systemic sclerosis.
Pulmonary fibrosis can be caused secondary to CREST syndrome, both limited and diffuse systemic sclerosis can lead to pulmonary fibrosis.
237
Hemophilia
X-Linked Recessive
Hemophilia A= Factor VIII deficiency (more common).
Hemophilia B= Factor IX deficiency.
Ⓝ bleeding time, Ⓝ PT, ↑ aPTT
aPTT is elevated because factors VIII and IX are only in the intrinsic pathway.
PT and bleeding time are always normal in hemophilia.
classical case school age child with Hemarthrosis (Bleeding into joints).
IV desmopressin (DDAVP) can be used as Tx for hemophilia A only (incr production of factor VIII)
238
Von Willebrand Disease (vWD)
Autosomal dominant condition.
↑ Bleeding time, Ⓝ PT, Ⓝ platelet count.
Vignettes will almost always give a presentation that entails a mix of one clotting factor problem (i.e., heavy menses, excessive bleeding after tooth extraction) and one platelet problem (i.e., usually mild, cutaneous findings such as petechiae, or epistaxis)
vWF has a secondary role where it helps stabilize factor VIII in plasma. Therefore, we sometimes get elevated aPTT in the condition, but that is not necessary aPTT maybe normal or elevated.
IV desmopressin (DDAVP) can be used as Tx.
239
Rubeola
High Fever & 3Cs ( Cough, Coryza, Conjuntivitis)
Koplik Spots (2-3days after symptoms)
As fever abates a Maculopapular rash starts at head and descends to cover whole body (like rubella)
240
Mumps
Classically presents as:
- Parotidits
- Orchitis
- Meningitis
Caused by Paramyxovirus.
241
Roseola Infantosum
Aka Sixths Disease
- Caused by HHV6 (Human Herpes 6 Virus)
- High grade Fever upto 104°F for 3-5days
Followed by Maculopapular Rash
- Spiking Fever followed by Rash
242
Peutz-Jeghers
Combo of Perioral Melanosis and Hamartomatous colonic polyps
Start colonoscopy at age 5 then do it every 1-2yrs
243
Duodenal Atresia
Bilious vomitting in Neonate.
Obstruction at level of duodenum or lower.
Assossiated with Down syndrome
Double Bubble sign on X-ray.
244
Pyloric Stenosis
Forceful/ Projectile Non-bilious vomitting in neonates.
Obstruction is above the level of duodenum.
Hypertrophic pylorous “ Olive shaped mass “ in abdomen.
Ultrasound for diagnosis.
245
Gardner Syndrome
FAP + Soft tissue ( i.e Lipoma ) or Bone tumors ( i.e of the skull )
246
Celiac disease
Intolerence to Gluten ( i.e gliadin protiens found in wheats, oats, rye and barley, but not in rice )
Causes Type-IV hypersenstivity response where T-cells attack the small intestinal villi, resulting in flattening of villi and malabsorbtion.
Anti-Endomysial ( AKA Anti-Gliadin ) antibody
Anti-Tissue Transglutaminase IgA
Patients with IgA deficiency have greater chance of developing celiac disease
Celiac disease present as vague bloating and diarrhea but can also cause Iron Def Anemia as iron absorbtion is impaired by flattening of villi.
Celiac disease has low Hb ( HY differential )
D-xylose test is abnormal as intestinal lining architecture is abnormal.
Assossiated with dermatitis herpitiformis and also cause increased risk of gastrointestinal T-cell Lymphoma ( Enteropathy- Assosiated T-cell Lymphoma EATL )
247
Lewy-Body Dementia
Parkinsonism + visual hallucinations + cognitive decline.
248
Whipple Disease
Caused by bacterium Troponema Whipplei.
Causes PAS positive macrophages in lamina propria of small bowel.
Can cause Arthritis and Diarrhea.
Tx: Antibiotics ( Doxycycline )
249
EBV Mononucleosis
Fever + Tonsillar exudates + Cervical lymphadenopathy + Cough + Hepatomegaly
250
Spontaneous Bacterial Peritonitis (SBP)
Cirrhosis + Fluid wave + Fever + Abdominal pain
Diabetic + undergoing peritoneal dialysis + Fever + Abdominal pain
251
Spontaneous Bacterial Peritonitis (SBP)
Cirrhosis + Fluid wave + Fever + Abdominal pain
Diabetic + undergoing peritoneal dialysis + Fever + Abdominal pain
TX: Ceftriaxone.
252
Charcots Triad
Jaundice , Fever (Rigors) , RUQ pain
For Ascending Colangitis
253
Charcots Triad
Jaundice , Fever (Rigors) , RUQ pain
For Ascending Cholangitis
254
Reynolds Pentad
Charcots Triad ( Jaundice , Fever (Rigors) , RUQ pain ) with Hypotension and Altered mental status.
For Ascending Cholangitis
255
Criggler Najjar Type-I
- Unconjugated bilirubin buildup;
- In newborn or infants;
- No UDP-GT;
- Phenobarbital yields no change
256
IgA Nephropathy
Aka Bergers disease
IgA deposition in Renal mesangium
Red urine 1-3days after sore throat, in contrast PSGN is red urine 1-3 wks after sore throat
IgA nephropathy is caused by viral infection not groupA strep.
Etiology includes Henoch-Scholen purpura;
- Palpable purpura (buttocks/ thigh)
- IgA nephropathy (red urine)
- Arthralgias
- Abdominal pain
257
Alport Syndrome
X-Linked disease:
- Mutation in collagen IV gene
- Patient who has red urine + eye or ear problem.
- Collagen IV is present in basement membrane of kidney, ear, eyes.
- Eye problems can be blurry vision/ cataracts
- Ear problems will be neurosensory hearing loss due to organ of corti dysfunction.
258
SIADH
( Syndrome of Inappropriate Anti-Diuretic Harmone )
Too much ADH (Vasopressin)
ADH is produced by supraoptic nucleus of hypothalamus and stored in posterior pituitary.
ADH increases water reabsorption in medullary collecting duct.
↓Serum Osmolality , ↓Serum specific gravity
↓ serum Na (< 135)
↑ Urine osmolality , ↑ Serum specific gravity
Tx :
– Demeclocycline (tetracycline causes insenstivity to ADH).
– Conivaptan & Tolvaptan (ADH receptor antagonists).
259
Diabetes Insipidus ( DI )
Central DI :
Not enough ADH secrection by hypothalamus or posterior pituitary is unable to release it properly
Tx : Desmopressin.
Can be caused by head trauma, meningitis or cancer.
Nephrogenic DI :
Insensitvity to ADH in kidney (serum ADH is ↑)
Caused by Lithium, demeclocycline, hypercalcemia, NSAIDs
Tx : NSAIDs + Thiazide.
Labs:
↑ Serum Sodium (>145),↑ Serum Osmolality,
↑ Serum specific gravity.
↓ urinary osmolality, ↓serum specific gravity.
260
Obstructive Lung Disease
Asthama, COPD, Old age.
PFT:
- FEV1↓ , FVC ↓ ,
- FEV1/FVC ↓(<70% ; Normal is 70%)
- TLC ↑
- RV ↑↑ , FRC (ERV-RV) ↑
261
Restrictive Lung Disease
Pulmonary Fibrosis, Pneumoconiosis etc
PFTs:
- FEV1 ↓, FVC ↓,
- FEV1/FVC ↑ (>70-80%)
- TLC ↓, RV ↓, FRC ↓.
262
SVC syndrome
Superior vena cava syndrome
Flushing of face + Congestion of neck veins.
Caused by pancoast tumor (Adenocarcinoma of Lungs)
263
NRDS (Neonatal Respiratory Distress Syndrome)
Aka hyaline membrane disease
Due to insufficient surfactant production by type II pneumocytes due to decrease in lamellar bodies (the specialized organelles that produce surfactant).
Decrease lecithin/sphingomyelin ratio (i.e., <2.0).
↓ surfactant production means ↓ alveolar compliance & ↑ elastic recoil.
CXR shows a “reticulogranular” appearance.
264
Acute respiratory distress
syndrome (ARDS)
Bilateral exudative chest infiltrates and decr O2 sats
in patient following: pancreatitis; aspiration of vomitus; near-drowning episodes (aspiration of fresh/sea water); improper insertion of NG tube into the lungs with feeding initiated; toxic shock syndrome; or general trauma / sepsis.
- Pulmonary decompensation associated with pancreatitis.
- Patient can be ventilated as follows: prone positioning (patient on
stomach) + low-tidal volume setting + permissive hypercapnia.
265
Pertussis
- Classic whooping cough presents as succession of many coughs
followed by an inspiratory stridor.
- Can also present in adults Cough with hypoglycemia or post-tussive emesis, which means vomiting after coughing episodes.
- Pertussis can cause super-high WBC counts in the 30-50,000-range, where there are >80% lymphocytes.
- One way to prevent = vaccination (TDaP)
266
Congenital diaphragmatic
hernia
- Caused by failure of formation of pleuroperitoneal membranes.
- Always occurs on the left, where bowel from the abdomen can herniate up into the left-chest.
- Can present as ↓ bowel sounds in the abdomen + ↑ bowel sounds in the left hemithorax.
267
Lyme Disease
Caused by Borrelia Burgdorferi, a spirochete transmitted by Ixodes tick in Northeast, Mid west, and West coast.
Erythema Migrans (Target shaped lesion ; Bulls Eye lesion) is first symptom.
After several weeks of dissemination;
- Neurological Symptoms: Cranial Nerve Palsy , Bells Palsy.
- Heart block (AV block).
- Arthritis (follows after months to years) due to immune complex type III hypersenstivity.
Tx: Doxycycline.
268
Neuroblastoma
- Adrenal medullary tumor in kids (< 4 yrs ).
- Irregular abdominal tumor, can cross the midline.
- Urine Metanephrines HVA (homovanillic acid)
VMA (vaniylmandelic acid).
- Homer-wright rosettes.
- N-myc oncogene.
- Bombesin +
- Neuron-specific enzyme +
* Opsoclonus (Dancing eyes)
* Myoclonus (Dancing feet)
269
Wilms Tumor
- Renal cell tumor in kids ( < 10yrs ).
- Smooth doesnot cross the midline.
- Elevated Metanephrines (HMA & VMA) in urine.
270
Pheochromocytoma
Adrenal Medulla tumor.
Short episodes of sympathetic hyperactivity:
- Palpitations
- Perspiration
- Pallor
- HTN (very high BP)
- Headaches
Elevated Catecholamines (Norepi, Epi)
Elevated Metanephrines (HMA & VMA) in urine
Tx:
Block adrenergic receptors
1- start with alpha blockers first
2- then start beta blockers (if u give beta blockers first it can kill the patient)
271
Hashimotos Thyroiditis
Hypothyroid
↑TSH , ↓T3 , ↓T4 , ↓Iodine uptake.
Leads to Thyroid gland Atropy
Aka Chronic Lymphocytic Thyroiditis.
Auto immune :
- Anti TPO antibodies
- Anti-Thyroglobulin antibodies
Has Hurthle cells and germinal centers on histology, Lymphocytic infiltrates are also seen.
Increased risk of Non-Hodgkins Lymphoma.
Assossiated with HLA-DR 5
Also assossiated with Thyroid Lymphoma
272
Congenital Hypothyroidism
Aka Cretinism.
Caused by:
1- Maternal Iodine deficiency (most common cause worldwide)
2- Congenital Thyroid abnormalities (most common cause in the developed countries)
Presents as;
- Hypotonia.
- Jaundice.
- 6 Ps
(Potbelly, Protruding Umbilicus, Protruding tounge, Puffy face, Pale, Poor brain development)
273
Graves disease
Hyperthyroidism.
↓ TSH, ↑ T3 , ↑T4 , ↑Iodine uptake.
Autoimmune (Stimulatory autoantibodies mimic TSH >> Hyperthyroidism).
- TSH receptor antibody (TRAb) aka TSI- thyroid stimulating immunoglobulin.
- Diffuse thyroid enlargement.
- Exopthalmos/ Proptosis
(Glycosaminoglycan accumulation in and around extra occular muscles)
- Peritibial myxedema
THYROID STORM:
- Fever, HTN, ↑CK.
- Sympathetic overload (Agitation, Diarrhea, Diaphoresis)
- Death (usually by arhythmia)
- Tx : Propanolol, PTU, Prednisone
274
Papillary Thyroid Carcinoma
- Most common thyroid cancer
- Excellent prognosis
- Assosiated with childhood radiation
- Lymphatogenous spread
- Finger-like or Nipple like projections on histo
- Orphan-annie eye nucleus on histology
- Pasamoma bodies may also be seen on histology.
Note : Thyroid cancers are not Hyperthyroid conditions.
275
Medullary Thyroid Carcinoma
- Parafollicular cell tumor >> ↑ Calcitonin.
- Assosiated with MEN syndrome
- Poor Prognosis- Hematogenous spread.
- Amyloid deposits in thyroid.
- Stained by Congo-Red stain.
Note : Thyroid cancers are not Hyperthyroid conditions.
276
Cancers with Psamoma bodies
“ PSaMM “
P = Papillary thyroid CA.
Sa = Serous cystadenoma/ adenocarcinoma.
M = Meningioma.
M = Mesothelioma.
277
Somatostatinoma
Delta-cell tumor >> Somatostatin.
- Global GI inhibition.
- Steatorhea.
- Gallstones.
- Mild diabetes.
Tx: Oral hypoglycemics
278
MEN Syndromes
(Multiple Endocrine Neoplasia)
Autosomal dominant syndromes
– MEN 1 : Menin gene
“ P P P “
Pituitary adenoma ,
Parathyroid adenoma ,
Pancreatic adenoma.
– MEN 2A : Marfanoid habitus
“ P M P “
Parathyroid adenoma,
Medullary thyroid carcinoma,
Pheochromocytoma.
– MEN 2B : Marfanoid habitus
“ P M N “
Pheochromocytoma,
Medullary thyroid carcinoma,
Neuromas (mucosal).
Both MEN 2A and 2B have RET gene mutation
279
CONN syndrome
Primary Hyper Aldosteronism
- Excess aldosterone secretion independant of RAAS.
- Renin level ↓
- Traid:
1- Hypertension
2- Hypernatremia
3- Hypokalemia
Other symptoms include:
Fatigue, Muscle cramping, chronic Headaches, Muscle weakness and pain.
280
Cushing Syndrome
Increase levels of Cortisol
(CRH >> ACTH >> Cortisol)
Caused by longterm Glucocorticoid use (MCC), Pituitary tumor (Cushings disease), Ectopic ACTH secreting tumor (SCLC), Adrenal tumor.
Symptoms:
- Moon faces
- Buffalo hump
- Central Obesity & Peripheral wasting/thinning
- Abdominal Striate (stretch marks)
- Skin/ Bone thinning
- In females it causes
> Loss of Libido.
> Menstural changes.
> Hirustism.
Dx :
– ↑ 24hr urinary free costisol.
– Low/High dose Dexamethasone test.
281
Sturge-weber syndrome
- Cutaneous Angioma over head & neck (Portwine stain).
- Focal/ generalized siezures.
- Hemiparesis.
- Intellectual disability.
Kids go on to develop Glaucoma.
282
Tuberous Sclerosis
AD mutation in Hamartin gene (chromosome 9) or Tuberin gene (chromosome 16).
- Hamartomas (can present anywhere in body).
- Siezures.
- Psychomotor delay.
- Intellectual disability.
- Adenoma sebaceum.
- Ash-leaf spot & Shagreen patches.
Also assosiated with kidney tumors known as Renal angiomyolipomas and heart tumor i.e Cardiac rhabdomyoma.
283
Chediak-Higashi syndrome
LYST gene : Defect in microtubule function.
Presents as;
“ C A I N “
C = Coagulopathy.
A = Albinism.
I = Infections.
N = Neuropathy.
284
Ataxia-Telangectasia
Defect in ATM DNA repair gene.
Presents as:
1- Ataxia.
2- Angiomas.
3- IgA deficiency.
285
CVID
(Common variable immune deficiency)
- Seen in Adults (3rd or 4th decade of life)
- Associated with increase Autoimmune disease and Lymphomas.
- Decrease plasma cells & Immunoglobins.
- Defective B-cells maturation
Note: B-cells number are normal but they are immature B-cells (lack IgM & IgD) thus can attack the body to cause autoimmune diseases or result in lymphomas.
286
Diseases associated with Hodgkins Lymphoma
1- Celiac disease
2- Hashimotos thyroiditis
3- Sjorgens syndrome
4- Wiskott-Aldridge syndrome
287
HIV CD-4 count association
- CD 4+ ≥ 500 = Strep.pnuemonia
- CD 4+ ≤ 200 = Pneumocystis Jeroveci
- CD 4+ ≤ 100 = Myco.avium & Toxoplamosis
- CD 4+ ≤ 50 = CMV
288
Lab values in anemia
289
Heme Synthesis
290
Glycolysis
291
Leukomoid Reaction
↑ WBCs, ↑Neutrophills, ↑Bands (left shift) (immature neutrophils)
↑Leukocyte ALP.
Leukomoid reaction can look like Leukemias and have the same labs too except in Leukemias there is low Leukocyte ALP.
292
Hodgkins Lymphoma
- Reed-Sternberg cells (Owl eye nucleus).
- Localized (single LN).
- Contiguous.
- Markers CD30+ & CD15+ are for Reed-sternberg cells & thus hodgkins lymphoma.
B-Symptoms:
- Low grade fever
- Night sweats
- Wt.loss
50% of hodgkins lymphomas are associated with EBV infection, Seen in bimodal age distribution as well as all subtypes are more common in men except Nodular sclerosing type which is 50-50 in men and women & also the most common subtype.
293
Non-Hodgkins Lymphoma
- No Reed-Sternberg cells (Owl eye nucleus)
- Multiple Nodes are involved
- Non-contiguous
- Often associated with HIV infections & Autoimmune diseases.
- Peak incidence in young adulthood (20-40yrs)
- Poor prognosis then Hodgkins disease.
- Types are:
> B-cells Lymphomas
> T-cells Lymphomas
294
Burkitts Lymphoma
- B-cell non hodgkins lymphoma.
- “ Stary Sky “ appearence on histology.
- C-myc gene translocation, t (8:14), t (8:22), t (2:8)
- Associated with EBV infection.
- African child with jaw lesion, or in american seen in adults involving abdomen & pelvis.
295
Cardiac Murmurs concept
Flow through the effected valve:
- ↑Blood Flow = ↑Intensity of Murmur.
- ↓ Blood flow = ↓ Intensity of Murmur.
Preload & Afterload can be changed by manuevers and can affect the murmurs:
- Inspiration & Rapid squatting >↑ intra thoracic pressure > ↑Venous return > ↑ Preload >↑Right sided murmur.
- Handgrip, Valsalva ↑ Afterload > ↓Intensity of the murmur ( VSD, MR, AR ).
296
Cardiac Action potential
297
Wolf-Parkinson-White syndrome
(WPW-Syndrome)
- Due to presence of accessory pathway conduction (bundle of kent).
- Shortened PR-interval, Widened QRS complex.
- Delta wave.
- Most common type of ventricular pre-excitation syndrome.
- No AV nodal delay for diastolic filling.
298
1st Degree Heart Block
- Benign & Asymptomatic
- Increase PR-interval (>200msec)
299
2nd Degree Heart Block (Type-I)
Mobitz type-I (Wenckebach) :
- Gradual prolongation of PR-interval until u get a P-wave which is not followed by QRS complex (Dropped beat).
300
2nd Degree Heart Block (Type-II)
Mobitz type-II :
- No prolongation of PR-interval
- Beat is dropped
- Problem in Bundle of His (fibrotic changes)
- Tx: Pacemaker
301
3rd Degree Heart Block
(Complete AV-block)
- Complete dissosiation of Atria & Ventricles.
- No synchronization between atria & ventricles.
- Ventricles are responding to Ectopic beats.
- Atria and Ventricles depolarize together and create P-wave on QRS or P-wave on T-wave.
- One of the HY cause of 3rd degree block is Lyme disease caused by Borriela Burdogferi.
302
Neonatal Herpes
- Caused by HSV-2 infection
- Characterized by:
> Vesicular Rash
> Encephalitis ( Siezures, CN palsies, Lethargy)
- Typically acquired during delivery.
- Usually occurs 2 weeks after birth no symptoms at birth.
303
Chagas Disease
Caused by Protozoa Trypanasoma Cruzii endemic to south america with reduvid bug (Kissing bug) as vector, it can also be transmitted person to person.
- Preferentially infects heart and myenteric nerves. Causing:
> Dilated Cardiomyopathy
> Heart failure
> Arrhythmias
Also assocaited with:
> Myocarditis
> Megaesophagus with achalasia
> Megacolon
Its one of the bugs that can cause heart block.
304
Medullary thyroid carcinoma
Derived from parafollicular (C) cells, which normally secrete calcitonin.
Histopathology of a thyroid mass shows amyloid deposits amongst nests of tumor cells.
305
What is pituitary apoplexy?
Acute pituitary hemorrhage.
It usually occurs in the setting of a preexisting pituitary adenoma.
Symptoms include:
1. Severe headache
2. Bitemporal hemianopsia (due to compression of the optic chiasm)
3. Ophthalmoplegia (due to compression of the oculomotor nerve [CNIII])
306
Tertiary hyperparathyroidism
Typically occurs in the setting of long-standing chronic kidney disease/end-stage renal disease (chronic parathyroid stimulation → parathyroid hyperplasia/autonomous hormone secretion).
It is characterized by:
- (↑) serum calcium
- (↑) serum phosphorus
- (↑) serum parathyroid hormone
307
Patient with hypocalcemia, hyperphosphatemia, elevated parathyroid hormone
These labs are consistent with (secondary) hyperparathyroidism, which is commonly caused by chronic kidney disease.
308
Neuroblastoma
- Young child with large abdominal mass.
- Urine shows elevated catecholamine metabolites.
- Biopsy shows small, round, blue tumor cells.
- This tumor is of neural crest cell origin.
309
Pseudohypoparathyroidism
Is characterized by parathyroid hormone (resistance).
Expected labs:
- (↓) serum calcium
- (↑) serum phosphate
- (↑) serum parathyroid hormone
Caused by defects in PTH receptor and downstream signaling (eg, Albright hereditary osteodystrophy).
310
Name 2 stains that indicate a tumor has neuroendocrine differentiation:
1. Chromogranin
2. Synaptophysin
Tumors derived from neuroendocrine cells characteristically show a salt and pepper chromatin pattern.
311
Waterhouse-Friderichsen syndrome is a potential complication of?
Meningococcemia.
It is characterized by bilateral hemorrhagic infarction of adrenal glands, resulting in acute adrenal insufficiency (eg, worsening shock).
312
Causes of high anion gap metabolic acidosis.
Anion gap = sodium − (chloride + bicarbonate)
(normal: 10-14 mEq/L)
(Mnemonic: MUDPILES)
1. Methanol
2. Uremia
3. Diabetic ketoacidosis
4. Propylene glycol/paraldehyde
5. Isoniazid/iron
6. Lactic acidosis
7. Ethylene glycol (antifreeze)
8. Salicylate (aspirin)
313
Types of renal tubular acidosis (RTA)
- Type 1 (distal):
Reduced ability to secrete (H+) in distal tubule (ie, H+ retention). Autoimmune diseases (eg, lupus, Sjögren syndrome) and amphotericin B toxicity.
- Type 2 (proximal):
Reduced ability to (reabsorb) (bicarbonate) in proximal tubule (ie, bicarbonate wasting). Carbonic anhydrase inhibitors, multiple myeloma, and Fanconi syndrome.
- Type 4:
Reduced production and/or response to (aldosterone). Diabetes mellitus, ACE inhibititors, nonsteroidal anti-inflammatory drugs, and heparin.
314
4 most common causes of renal papillary necrosis.
1. Sickle cell disease/trait
2. Chronic analgesic use (eg, nonsteroidal anti-inflammatory drugs)
3. Diabetes mellitus
4. Acute pyelonephritis
315
Which anesthetic used in rapid-sequence intubation is associated with severe hyperkalemia?
Succinylcholine,
A depolarizing neuromuscular blocker that binds postsynaptic acetylcholine receptors and triggers sodium influx and potassium efflux. Has rapid onset and offset but can cause life-threatening cardiac arrhythmia due to severe hyperkalemia.
316
White blood cell casts are diagnostic of?
Pyelonephritis
317
Lupus nephritis occurs primarily due to?
Deposition of DNA/anti-DNA immune complexes within the glomerulus (e.g., mesangium, subendothelial or subepithelial space).
318
Occupational exposures to rubber, plastic, and aromatic amines are risk factors for which cancer?
Urothelial bladder cancer
319
Extrarenal manifestations of autosomal dominant polycystic kidney disease.
1. Liver: cysts
2. Neurovascular: intracranial berry aneurysms
320
Poststreptococcal glomerulonephritis
Shows a (granular) pattern of immunofluorescence composed of IgG, IgM, & C3 deposits along the glomerular basement membrane and mesangium.
321
Bartter syndrome
Characterized by a reabsorption defect in the (thick ascending loop of Henle) (Na/K/2Cl transporter) and mimics chronic (loop) diuretic use (alkalosis, hypokalemia, hypercalciuria).
322
Gitelman syndrome
Characterized by a reabsorption defect in the (distal convoluted tubule) and mimics chronic (thiazide) diuretic use (alkalosis, hypokalemia, hypercalciuria).
323
Renal cell carcinoma is often associated with paraneoplastic syndromes involving ectopic production of the following hormones (PEAR mnemonic).
1. Parathyroid hormone-related protein (hypercalcemia)
2. Erythropoietin (erythrocytosis)
3. Adrenocorticotropic hormone (Cushing syndrome)
4. Renin (hypertension)
324
List 4 common symptoms of acute cystitis.
1. Dysuria,
2. Suprapubic pain,
3. Urinary frequency,
4. Urinary urgency.
325
Acute Interstitial Nephritis
White blood cell casts, sterile pyuria, and urine eosinophils
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Causes of hypophosphatemia
1. Internal redistribution
2. Decreased intestinal absorption
3. Increased urinary excretion
327
Parkinson disease (TRAP mnemonic)
- Tremor
- Rigidity
- Akinesia/bradykinesia
- Postural instability (late finding)
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Amyotrophic lateral sclerosis
UMN: degeneration & atrophy of lateral corticospinal tracts, precentral gyrus
LMN: degeneration of anterior horn (thin anterior roots) & cranial nerve motor nuclei
Muscle: denervation atrophy (angular fibers with crowded nuclei)
Clinical manifestations:
UMN symptoms: spasticity, hyperreflexia, pathologic reflexes
LMN symptoms: muscle weakness, atrophy, fasciculation
Treatment
Riluzole: reduces glutamate-induced excitotoxicity & improves survival
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Localizing signs: Brain Lesions
- Eyes will look (toward) a stroke and (away from) a seizure.
- Uvula will deviate (away from) the lesion.
- Jaw will deviate (toward) the lesion.
- Shoulder will droop (ipsilateral) to the lesion.
- Tongue will deviate (toward) the lesion.
330
What is the triad of Wernicke encephalopathy?
What structure is affected?
- Ataxia, ophthalmoplegia (Nystagmus), and encephalopathy (Confusion).
- Mamillary body are affected.
- Cause: Thiamine deficiency (Alcoholics)
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Gerstmann syndrome
- Agraphia (inability to write)
- Acalculia (inability to solve mathematical calculations)
- Finger agnosia (inability to identify individual fingers on the hand)
- Left-right disorientation
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Myasthenia gravis
Autoantibodies against nicotinic acetylcholine receptors on the (post) synaptic membrane of the neuromuscular junction
Associated with Thymoma
333
Lambert-Eaton syndrome
autoantibodies against voltage-gated calcium channels on the (pre) synaptic membrane of the neuromuscular junction
Associated with Small cell lung cancer (SCLC)
334
Achondroplasia
- Achondroplasia is an autosomal (dominant) condition.
- It is caused by a mutation in FGFR3 gene, which causes an inhibition
of (chondrocyte) proliferation.
335
Name the clinical manifestations of systemic lupus erythematosus (RASH OR PAIN mnemonic).
Rash (malar)
Arthritis
Serositis (pericarditis, pleuritis)
Hematologic abnormalities (cytopenias)
Oral/nasopharyngeal ulcers
Renal disease
Photosensitivity
Antinuclear antibodies
Immunologic disorder (anti-dsDNA, Anti-Smith, antiphospholipid)
Neurologic disorders (psychosis, seizures)
336
Give the classic tetrad of IgA vasculitis (Henoch-Schonlein purpura).
1. Palpable purpura without thrombocytopenia or coagulopathy (typically over the posterior lower extremities and buttocks)
2. Arthritis/arthralgia
3. Abdominal pain (due to localized bowel wall inflammation; patients are at risk of intussusception)
4. Kidney disease (hematuria +/- proteinuria)
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Eosinophilic granulomatosis with polyangiitis typically presents with:
1. asthma, sinusitis
2. peripheral neuropathy (mononeuropathy multiplex)
3. subcutaneous nodules or purpura
The heart, gastrointestinal system, and kidneys can also be involved. IgE levels are elevated.
338
A middle-aged woman with joint pain, dry eyes, and dry mouth has extensive lymphoid infiltrate with germinal centers on excision of a salivary gland. What is the diagnosis?
Sjogren syndrome.
Positive anti-Ro (SSA) &/or anti-La (SSB)
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Patient with chronic hepatitis C presents with hematuria and proteinuria. Renal biopsy shows hypercellular glomeruli and thickened capillary walls with a "tram track" appearance. What is the diagnosis?
Membranoproliferative glomerulonephritis
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CREST Syndrome
1. Calcinosis: calcium deposits in the skin
2. Raynaud phenomenon: blood vessel spasms in response to cold or stress
3. Esophageal dysfunction: acid reflux +/- decrease esophageal motility
4. Sclerodactyly: thickening of skin over hands and fingers
5. Telangiectasia: dilation of capillaries on surface of skin
341
A young adult who smokes and has painful ulcers with dry gangrene on the toes but normal pulses in the foot most likely has?
Buerger disease (thromboangiitis obliterans).
Histopathology reveals segmental inflammatory intramural thrombi of medium and small vessels
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A 55-year-old woman presents with unilateral headache, transient vision loss, and jaw claudication. What is the diagnosis?
Giant cell arteritis.
The screening test for this condition is (erythrocyte sedimentation rate [ESR]). A (temporal artery biopsy) is typically obtained to confirm the diagnosis.
