Final Mix Flashcards
Lead poisoning
Inhibits Ferochelase and ALA dehydratase
^ ALA/ Protopophyrin
*Macrocytic anemia, Kidney dz
BASOPHILIC STIPPLING
Langerhans histocytosis
Birbeck granules (tennis racket)
Lytic bone lesion + rash and otitis media
Glanzman Thromboblasthenia
Decreased GpIIb/IIIa- aggregation defect
Hodgkins Lymphoma
Reed Steinberg cells
Continuous spread EBV associated
-Generally good prognosis
Prognosis better when Lymphocytes>Reed steinberg
Usually in younger or older
Fever, weight loss, night sweats,
Essential Fructosuria
Fructokinase D (AR)
Benign
fructose in urine
McArdle DZ
MYOPHOSPHORYLASE (skeletal M glycogen phosphorylase) D AR
*^ Muscle glycogen, painful muscle cramps and osmotic lysis of muscle cells with exercise.
*rare arrhythmias
Pompe DZ
Lysosmal alpha 1-4 Glucosidease D (AR)
*endsosomal glycogen deposits
*CARDIOMYOPATHY –>Death (heart)
*SYSTEMIC DISEASE –>Death (liver muscle)
Folate B9
Deficiency: Phenytoin, sulfonamides, MTX
*Increased cysteine with normal methylmmmalonyc acid
Glycolysis
PFK1
^AMP, F2-6P
v ATP, Citrate
De Novo Purine Synthesis
PRPP amidotransferase
v AMP, IMP, GMP
Minimal Change Dz
Nephrotic
LM-Normal
EM- Foot process effacement
*Kids
*infection, immunization etc.
*Hodgkins
TX: CORTICOSTEROIDS
Acute Intermittent Pophyria
Porphobilinogen Deaminase D causes ^ PORPHOBILINOGEN ,ALA, Coporhobilinogen
*Early Heme synthesis
*Painful abdomen, PORT WINE URINE- darkens on standing, Polyneuropathy, psychological
*PRECIPITATED BY DRUGS, ETOH, STARVATION TX: Glucose and HEME –IALA synthase
Irreversible enzymes of Gluconeogenesis
Pyruvate carboxylase
PEP carboxyKinase
F1-6Pase
G6Pase
Tay-Sachs disease
Hexosaminidase A D (AR) Buildup of GM2 GANGLIOSIDE
*Cherry red spot on macula,
ONION SKINNING of lysosomes
*Progressive neurodegeneration
DEATH BY AGE 4
Urea Cycle
Carbamoyl phosphate synthetase I
^ N-Acetyl glutamate
Diffuse Proliferative GN
SLE/MPGN “Wire looping” of capillaries
SubENDOthelial and intramembranous IgG with C3 deposition
NEPHROTIC OR NEPHRITIC
MOST COMMON CAUSE OF DEATH IN SLE
HUS
Hemolysis, uremia, thrombocytoopenia
Post EHEc common
Lysosomal Storage Diseases
I Cell DZ
Fabry
Gauchier
Niemann-Pick
Tay Sachs
Krabbe
Metachromatic leukodistrophy
Hurler syndrome
Hunter Syndrome
Von Gierke DZ
G6Pase D (AR)
*Severe fasting hypoglycemia
*^ Glycogen in liver/ HEPATOMEGALY
*^ Blood lactate
TX: Oral cornstarch and frequent feeding.
Avoid galactose and fructose
Membranous Nephropathy
Nephrotic LM- diffuse capillary and GBM thickening
IF- granular immune deposition
EM- Spike and Dome w/SUBEPITHELIAL deposits
*Most common 1ary caucasian nephrosis
*Anti-phospholipid A2 receptor
*HBV, HCV, SLE, TUMOR
RPCGN
Goodpasture Wegener’s GPA
Microscopic polyangiitis
Crescent moon shaped fibrin, protein, and leukocyte infiltration
Classic Galactosemia
Galac1P Uridyltransferase D (AR) causes ^GALACTITOL
*Infantile Cataracts
*Failure to thrive
*jaundice
*hepatomegaly
*intellectual Disability
TX: Exclude galactose and Lactose from diet
Kawasaki disease
Fever 4 days + CRASH - Conjunctivitis, Rash, Adenopathy, Strawbery tongue, Hands and feet.
*Necrotising vasculitis of medium arteries including coronaries (risk for aneurysm/thrombosis/rupture)
TX: IVIG and ASPIRIN
IL12R Deficiency
Decreased Th1- TB all the time (and fungal)
v IFN gamma (treat with supplemental)
Acute post strep GN
Hypercellular glomeruli with “lumpy bumpy” immune complexes along BM and mesangium
SubEPITHELIAL humps on EM
cola colored urine, HTN, decreased complement levels
N-Acetylglutamate deficiency
Needed for CPS 1 –> hyperammonemia ^ornathine without orotic aciduria
Normal urea cycle enzymes/ No enzyme deficiency
Maple Syrup Urine Disease
Alpha Keto-acid Dehydrogenase D (AR) B1 FAD NAD dependent
I Love Vermont- Isoleucine, Leucine, Valine
*CNS Defects
*Intellectual diability
*death
TX: Restrict ILV, Thiamine supplement
Nephrotic syndrome
>3.5g Proteinuria
Hyperlipidemia Fatty casts
Thromboembolism (ATIII loss)
^ Risk of infection
FSGS, Membranous Nephropathy, Minimal change Dz, Amyloidosis, Membranoprolferative GN, Diabetic Glomerulonephropathy
Weber syndrome
Paramedian stroke
*Ipsilateral Oculomotor nerve palsy
*Contralateral Hemiparesis
*Contralateral Hypoglossal palsy
*Contralateral parkinsonism
B6 Pyridoxine
Pyridoxal Phosphate Vital to ALT and AST function
Transamination, decarbox, glycogenolysis, many neurotransmitters etc Defieciency-
*GABA deficiency- Convulsions, hyperirritability, peripheral neuropathy
*Can be caused by INH and OCP
*Sideroblastic anemia
Follicular lymphoma
t14:18 IgG BCL2
vApotosis Adults Indolent with “WAXING AND WANING LYMPHEDENOPATHY
Hartnup Dz
Cant uptake neutral AA Tryptophan/ Niacin Deficiency
*Pellagra: Dermatitis, diarrhea, dimentia
TX: Niacin supplements
Focal Segmental Glomerulosclerosis
Nephrotic
LM- Segmental sclerosis and hyalinosis LM
EM- Foot process effacement- Like minimal change
AA/Hispanic HIV, SS Dz, Heroin abuse, Obesity, IFN treat, CKD- congenital or removal
Niacin- B3
NAD factor- can be derived from tryptophan
Deficiency- Pellagra
*Dermatitis *Dementia *Diarrhea
Excess- Facial flushing Hyperglycemia Hyperuricemia
Alport syndrome
IV collagen problem
BM thinning Glomerulonephritis, deafness, eye problems
“Cant pee, cant see, cant hear high C”
Temporal Giant Cell Arteritis
Most common in elderly females
Unilateral headache
Focal granulomatous inflammation of carotid artery branches
can cause blindness due to ophthalmic occlusion.
TX: CORTICOSTEROIDS
Associated with Polymyalgia rheumatica
Alport syndrome
IV collagen problem BM thinning Glomerulonephritis, deafness, eye problems “Cant pee, cant see, cant hear high C”
Mantle cell lymphoma
Older males
- 11:14 translocation
- IgG and Cyclin D
Gaucher DZ
MOST COMMON GLUCOCEREBROCIDASE D (XR) leads to ^ GLUCOCEREBROSIDE
*hepatosplenomegaly
*pancytopenia
*Aseptic necrosis of femur
*bone crises
*Gaucher Cells- LIPID LADEN MACs RESEMBLING CRUMPLED TISSUE PAPER
TX:rGLUCOCEREBRSIDASE
Acyl- CoA Dehydrogenase D
*decreased FA B- Oxidation *v Gluconeogeneis (Acetyl CoA is activator) * Decreased fasting glucose
I-Cell DZ
Problem attaching M6P to lysosomal proteins in golgi (phosphotransferase D)
Proteins secreted instead (in secretory granules)
*Coarse facial features
*Clouded corneas
*Restricted joint mvt.
*high plasma lysosomal proteins
OFTEN FATAL IN CHILDHOOD
Adenosine Deaminase deficiency
(AR) Purine salvage deficiency causing hyper ATP and dATP Negative feedback on purine synthesis Results in a severe combined immunodeficiency -Failure to thrive -Chronic diarrhea -Recurrent infections of all types (Signs: No thymic shadow, v TRECs, no T cells
IgA nephropathy
Mesangial proliferation with Mesangial Immune Complexes
Henoch- schonnlein purpura
URI/ gastroenteritis preceeding
Hematuria, RBC casts, arthritis, rash
Gluconeogenesis
F1-6Pase
^ATP , Acetyl CoA
v AMP, F2-6P
Cori DZ
Debranching Enzyme D (AR)
*Branched Glycogen in liver
*Mild hepatomegaly and low fasting glucose
Mycoses fungoides- Sezary
Cerebreform nuclei CD4+
cutaneous patches and lymph tumors
Indolent course
Alkaptonuria
HOMOGENSAtE OXIDASE D (AR)
*Cant degrade tyrosine
*Benign darkening of connective tissue
*Dark urine on standing DEBILITATING Arthritis
Wallenberg syndrome
Lateral medullary syndrome
PICA Vestibular nuclei, lat. spinothalamic, spinal trigem nuc. nuc ambiguous Sympathetics, inferior cerebellar peduncle
*Vertigo/nystag/vomiting
* v Pain and temp IPSILATERAL face, CONTRALATERAL body
*Dysphagia, hoarseness,
v gag
*Ipsilateral Horner
*ataxia, dysmetria
TCA Cycle
Isocitrate Dehydrogenase
^ADP
v ATP, NADH
Niemann-Pick disease
Sphyngomyelinase deficiency (AR) leads to accumulation of SPHINGOMYELIN
*Seen in CNS and cerebellum
*HEPATOSPLENOMEGALY
*Progressive neurodegeneration
*cherry red spot on fundoscopic examiniation
*“Foam cells”
TTP
ADAMS13 D
*Increased thrombosis- vWF multimers
*Schistocytes,
^LDH
NASTY FEVER TORCHED HIS KIDNEYS
Neuro, Fever, Thrombocytopenia, Hemolysis, Kidney failure
Autosomal Recessive disorders
ABCDEFGH SPW Albinism/Alpha1AT, Beta thal, CF/CAH, Dubin johnson/deafness, Enzyme Ds(lysosome/glycogen storage), Friedrichs Ataxia/Fanconi, Galactosemia, Hemochromatosis Sickle cell, PKU, Wilsons
Vitamin A
Antioxidant -differentiation of epithelial cells
-Adjunct to measels treatment,
PML treatment,
Acne (isotretinoin)
Deficiency- Night blindness, dry skin/alopecia, immune D Excess- Pseudotumor cerebri, alopecia and skin changes, Hepatic abnormatities, Cleft palate/Cardiac defects
FA Oxidation
Carnitine Acyltransferase I / Carnatine Palmitoyl Transferase I
v Malonyl CoA
Atypical antipsychotics
Olanzapine, clozapine, quetiapine, risperidone, aripiprazol, ziprasodone
Cystinuria
COLA transporter D (AR)
*Hexagonal renal cysteine stones
*2 Cysteine covalently bonded
TX: Alkalinize urine (acetazolamide), and Chelating agents
Henoch-Schonlein Purpura
Most common childhood vasculitis following URI
IgA Complex deposition
*Palpable purpura lower extremities
*Arthralgia
*Abdominal pain, melena
Can cause IgA nephropathy
FA synthesis
Acetyl CoA carboxylase
^ Insulin, Citrate,
v Glucagon, Palmitoyl CoA
AD hyper IgE (Job)
Stat mutation- No neutrophil recruitment
FATED- course Faces, Abscesses(cold), Teeth(primary retained), IgE, Derm- eczema
^ IgE, v IFN gamma
Riboflavin
FAD- Component of dehydrogenase reactions (TCA cycle)
Deficiency- Chelosis, Corneal vasculization, dementia, glossitis
Acute post strep GN
Hypercellular glomeruli with “lumpy bumpy” immune complexes along BM and mesangium SubEPITHELIAL humps on EM cola colored urine, HTN, decreased complement levels
Homocysteinuria
CYSTATHIONE SYNTHASE D (cant make cysteine) or HOMOCYSTEINE METHYLTRANSFERASE D (cant make methionine)
*^ Homocysteine in urine
*intellectual disability
*tall with Kyphosis and osteoporosis
*Down and in lens subluxation
*Atherosclerosis/ Thromboembolism/ Stroke (EVEN IN KIDS)
TX: Increase cysteine or methionine, B12/B6 supplementation
ITP
usually post infectious in kids
*Anti GpIIb/IIIa ab
*Thrombolysis,
^ Megakaryocytes on BM smear
Marginal maltoma
Associated with sjogrens , hashimoto thyroiditis, and H pylori
Krabbe Leukodystrophy
Galactocerebrosidase D (AR) leads to ^ GALACTOCEREBROSIDE psychosine
*peripheral neuropathy
*Developmental delay
*optic atrophy
*globoid cells
FATAL BEFORE AGE 2
PAN
Polyartaritis nodosa
* “rosary sign” micro-aneurysms and spasms
* Immune complex involvement of medium sized renal and visceral vessels
*Transmural inflammation with fibrinoid necrosis
*Associated with Hep B Fever, weightloss, malaise, headache, abdominal pain, melena, HTN, neurologic dysfunction
TX: CORTICOSTEROIDS, CYCLOPHOSPHAMIDE
Thromboangiitis Obliterans
(Buerger DZ) Heavy smokers, male >40 Segmental thrombosing vasculitis
*Claudication causing gangrene, autoamputation, superficial nodular phlebitis and raynauds.
TX: SMOKING CESSATION
Burkitt Lymphoma
8:14 translocation C myc
Starry sky appearance
EBV associated Jaw lesion in africa
Glycogenolysis
Glycogen Phosphorylase
^Epi, glucagon, AMP
v G6P, insulin, ATP
High potency antipsychotics
Try to Fly High
Trifluoperazine, fluphenazine, Haloperidol
PARKINSONISM
Fragile X
v FMRI Xlinked
*intellectual disability
* Big balls
*Large Jaw
*Large everted ears
*autism
*Mitral prolapse
ALL
Tcell variety= mediastinal mass
Bone pain Spreads to CNS and testes
Good response to chemo
t(12:21) confers better prognosis DOWNS association
Glycogen Synthesis
Glycogen Synthase
^G6P, Insulin, Cortisol
v Epi, Glucagon
Porphyria Cutanea Tarda
UROPOPHRYHOGEN DECARBOXYLASE D
- ^ Uroporphyrin
*BLISTERING PHOTOSENSITIVITY
*Liver involvement
*Tea colored urine
*hypertrichosis
*facial pigmentation
*HepC, Alcoholism, LFTs
Ataxia Telangectasia
DS DNA breaks Cerebellar defects, telangectasia IgA deficiency ^ AFP, v IgA,G,E
Bernard Soulier
decreased GpIb –> Decreased ADHESION to vWf
Takayasu Arteritis
“pulseless disease”
Granulomatous involvement of aortic arch and great vessels
Young asian females
Fever, night sweats, arthritis, myalgias, skin nodules, ocular disturbances
TX:CORTICOSTEROIDS
Galactokinase D
AR Galctose in blood and urine (maybe galactitol)
*Infantile cateracts lack of tacking/ social smile
Diabetic Glomerulonephropathy
Mesangial expansion with GBM thickening.
Eosinophilic nodular glomerulosclerosis “Kimmelstein wilson lesions”
Glycosylation of GBM –> Permeability
Glycosylation of efferent arterioles—> mesangial expansion
Metachroomatic Leukodystrophy
ARYLSULFITASE A D (AR) leads to ^ CEREBROSIDE sulfate
*Central and peripheral demyelination
*Ataxia
*Dementia
METACHROMATIC staining
Biotin B7
Carboxylation enzymes:
Pyruvate–>OAA
Acetyl CoA->Malonyl CoA
Pripionyl CoA –> Methylmalonyl
CoA Deficiency: Caused by a ton of raw egg whites or antibiotics
*Dermatitis, alopecia, enteritis
Leukocyte adhesion deficiency
LFA1 defect
Bacterial infections, impaired healing, delayed umbilical separation
Neutrophilia from decreased margination
Membranoproliferative glomerulonephritis
Type I - SubENDOthelial immune complex deposits with granular IF-
TRAM TRACK appearance
HBV, HCV, Lupis, Subacute bacterial endocarditis
Type II -Intramembranous
DENSE DEPOSITS. LOW C3
Brouton agammaglobinemia
X-Linked BTK (Bcell Tyrosine Kinase) deficiency
No adult BCL count
no pro B cells and low Ig(AMGDE)
Bacterial and viral infections
Common variable deficiency
v B cell differentiation
BRONCHIECTASIS in normal 20-30 yo female (sinopulm infections)
v Plasma cells and IG
AML
(PML with 15:17) >20% blasts in periphery or >20% in BM
Aurer rods/ faggot cells
Treat with retinoic acid
Can come from myeloproliferative disorders
>60 YO DIC common presentation
Hereditary hemorrhaghic telangectasia
Telangectasia, epistaxis, AV malformations, GI bleed hematuria
Osler-Weber-Randau
Chronic granulomatous dz
X linked NADPH oxidase D
^ catalase + organisms
PLACESS Pseudomonas, listeria, Aspergilis, Candida, Ecoli, Staph, Seratia
Dihyrorotamine and nitroblue test
Cholesterol Synthesis
HMG CoA reductase
^Insulin, T4
v Glucagon, Cholesterol
B5 (pantothenate)
CoA part - fatty acid synthesis
Deficiency -Dermatitis, enteritis, alopecia, adrenal insufficiency
Hurler Syndrome
alpha-L-IRONIDASE D (AR) causes ^ HEPARAN & DERMATAN sulfate *Gargoylism *Devo delay *airway obstruction *corneal clouding *hepatosplenomegaly
Wiskott-Aldrich
X recessive
WATER Wiskott Aldrich
Eczema
Recurrent infections
v IgM,G
^ IgA, E
GPA
Wegeners Granulomatosis with Polyangiitis
Focal necrotizing vasculitis with granuloma formation
*Perforation of nasal septa, chronic sinusitis, OM, Mastitis
*Hemoptysis, cough, dyspnea
*Hematuria, red cell casts
+cANCA (Anti-neutrophil cytoplasmic antibody)
TX: CORTICOSTEROIDS, CYCLOPHOSPHAMIDE
Thiamine B1
Part of TTP- necessary in many dehydrogenase reactions
*Pyuvate/ alpha ketoacid dehydro/Transketolase/ Branched chain keto Deficiency-
*Confusion/ophthalmoplegia/ataxia
*Confabulation, personality change- Medial thalamus and mamillary bodies
*Dry Beriberi- Polyneuritis/muscle wasting
*Wet beriberi- High output cardiac failure
*** Give thiamine with glucose to hypoglycemic at risk for deficicency**
Carnetine D
Unable to transport LCFA into mito for Oxidation
*Weakness/hypotonia
*Hypoketotic hypoglycemia
De Novo Pyrimidine synthesis
Carbamoyl phosphate synthetase II
Autosomal Dominant Diseases
MMOOCHA STAND
Marfan/MEN, OI/Osler-weber-rendu, Cholesterolemia, Huntington/vHL, ADPKD/Achondroplasia, Spherocytosis, Tuberous sclerosis, Adenosis polposis, Neurofibromatosis 1/2, Dystrophies myotonic
Hunter Syndrome
IDURONATE SULFATASE D (XR)
^ HEPARIN DERMATAN SULFATE
*Mild Hurler + Aggressive behavior
*No corneal clouding
Fabry Dz
ALPHA GALACTOSIDASE A D (XR)
Buildup of CERAMIDE TRIHEXOSIDE
*Peripheral neuropathy
*ANgiokeratomas
*CV/Renal DZ with mesenteric ischemia
Churg-Strauss
Associated with ASTHMA
EOSINOPHILIC granulomatous necrotizing vasculitis
+pANCA and ^IgE
*Asthma, sinusitis, palpable purpura, PERIPHERAL NEUROPATHY
Diffuse Large B Lymphoma
T 14:18- ^BCL2 = v Apoptosis
Most common in adults
CML
t9:22 BCR-ABL constituative kinase Increased myeloid cells
Splenomagaly 45-85 yrs
Imatinib treatment
Lesch Nyhan
HGPRT Deficiency (XR)
*Excess uric acid production leading to gout
*intellectual disability
*self mutilation
*aggression
*dystonia
TX: Allopurinol and Febuxostat
SLL/CLL
Small/chronic lymphocytic leukemia
- B cell leukemia
>60 year olds
SMUDGE CELLS
autoimmune hemolysis
HMP Shunt
G6PD
^NADP+
v NADPH
Adult T Lymphoma
HTLV1- retrovirus Cutaneous and bone lesions Japan, west Africa, carribean
Chedak Higashi
Lysosomal trafficking
*Pyogenic infection
*Partial albinism
*Neuropathy/neurodegen
Inclusion in neutrophils and platelets- Pancytopenia common
Ketogenesis
HMG CoA Synthetase
SCID
Aensine deaminase or IL2 Receptor D
*Failure to thive
*Diarrhea
*Recurrent infections
v TRECs, no thymus
TX: BMT
Hairy cell leukemia
B cell leukemia with pseudopod appearance Older adults TRAP+
Fructose intolerance
Aldolase B D (AR)
^ F1P and v Available phosphate
*Hypoglycemia
*Jaundice/Cirrhosis
*Vomiting TX: Eliminate fructose and Sucrose from diet
Ornithine Transcarbamylase D
XR Defect in ornathine + carbamoyl phosphate –> Citruline
Carb Phosphate converted to OROTIC ACID
*^OOROTIC ACID
*^ BUN
*Hyperammonemia and hepatic encephalopathy- (Slurring of speech, somnolence, vomiting, cereberal edema,vision problems)
TX: decrease protein, give BENZOATE, BIOTIN, PHENYLBUTYRATE
G6P D
XR - African americans
*Inability to produce NADPH - cant reduce glutathione
Hemolysis with oxidative stress (fava beans, sufa, primaquine/chloro, Anti TB drugs)
*Heinz bodies and Bite cells
Pyruvate Dehydrogenase Deficiency
^ Pyruvate
*Lactic acidosis (2/2 LDH)
*Neuro defects
*Increased alanine (2/2 ALT)
TX: KETOGENIC FOODS (fats) and AA(Lysine Leucine)
PKU
PHENYLALANINE OH-ASE D or BH4 D (AR)
^ Phenylketones in urine- v aromatic acid metabolism
*intellectual disability
*Mousy/musty smell
*Fair skin
*Eczema
*Growth retardation
TX: Avoid aspartame, dairy, meat, fish, chicken, beans, nuts- BH4 sup.
Low potency Antipsychotics
Cheating Thieves are Low
Chlorpromazine, Thoradiazine
