What CD receptor do neutrophils express
What role does PGI have
PGI = Platelet gathering inhibitor
What role do Mast Cells have
Release Histamine Vasodilation and increase vascular permeability
What is the second phase response of Mast Cells
4 Mediators that call in Neutrophils
LTB4, C5A, IL-8, bacteria products
Classical compliment system
(ig) GM makes Classic cars (C1)
Pathway/end result of compliment system
C3, C5, generation of membrane attack complex (MAC)
What components of compliment system trigger mast cell degranulation
C3a and C5a
one role of C5 in the compliment system
Calls in neutrophils
What does bradykinin do?
Same thing as histamine increase vasodilation, vascular permeability (++pain)
E2 fEEEEEver and pain
mediators that macrophages release
TNF-g, IL-1 Stimulate cox for PGE2 for fever
Leukocyte migration and rolling what are the binding factors
E-selectin, P-selectin Binds the Sialyl-Lewis
Leukocyte adhesion of vessel wall
ICAM (intercellular adhesion molecule)
Delayed separation of umbilical cord
Leukocyte adhesion deficiency (LAD) CD18
Lack of pus formation
Leukocyte adhesion Deficiency
Impaired phagolysosome formation
Whats the mechanism of O2 to HOCl (bleach) in a phagocyte degredation
O2 --> O2- --> H2O2 --> HOCL
What is the defect in Chronic Granuloma Dz (CGD) aka poor O2 dependent killing
Defect in NADPH
Maturation process of T cells. where they from and where do they go?
T cells are made in the bone marrow and mature in the thymus
Which T cells recognize which MHC class
CD4 t cells recognize MHC class 2 CD8 t cells recognize MHC class 1
CD4+ T cell activation requires what? (2 signals involved in activation) And what is their role
Antigen presenting cells (APCs) phagocytize antigen, process it, then present it on its MHC 2 membrane//B7 (on APC) binds to CD28 on MHC2 CD4 release cytokines to help in inflammation
What do CD4 helper T cells do?
They help both CD8+ / Bcells Broken into 2 subsets Th1 helps CD8 Th2 helps with B cells
Th1 helps what cells and how?
Th1 helps CD8 cells by releasing IL-2 (t cell growth factor and activator) and IFN-g (macrophages)
Th2 helps what cell and how
B cells IL-4 (class switching to gig and igE) IL-5 (Eosinophil chemotaxis and activation/maturation of B cells)
Whats a main enzyme that triggers apoptosis
B Lymphocyte maturation process
immature B cells are made in the bone marrow Undergo ig rearrangement to become naive B cells that express surface antigens IgM and IgD
B cell activation requires 2 signals
B cell presents antigen to CD4 via MHC 2 CD40 receptor (on Bcell) binds to CD40L on b cell
Marker for hematopoietic stem cell (in bone marrow)
Stem cell of the lung
Type 2 pneumocytes
When converting type 3 collagen to type 1 collagen , which enzyme is used and what does it require as a cofactor
Tumor cell neoplasia is (monoclonal or polyclonal)
3 things to think about when you see an enlarged lymph node
Metastatic cancer Reactive hyperplasia (simple infection) Lymphoma
What is a main cause of neuronal tube defects
Anencephaly is associated with what involving the amniotic fluid
Polyhydramnios - too much amniotic fluid because the baby doesn't have a developed brain to swallow it
Whats syringomyelia? and what brain malformation is associated with it
Degeneration of the spinal cord "CAPE/SHAWL-like" bilateral loss of pain and temp in upper extremities usually associated with Chiari malformation
Whats chiari malformation
herniation of the vermis through the foramen magnum
What is ALS (Amyotrophic Lateral Sclerosis)
Degenerative disorder of the upper and lower motor neurons (corticospinal tract) zinc copper superoxide dismutase mutation (SOD- removes free radicals)
Degenerative disorder of the cerebellum Fred the FRAT star - mess up of Frataxin (iron binding protein) staggering and falling but has a sweet big heart diabets and hypertrophy cardiomyopathy GAA
What is the classic triad of meningitis
Stiff neck, headache, fever
How do you differentiate the etiology of meningitis when looking at the CSF via lumbar puncture
Bacterial- neutrophils with low CSF glucose Viral- lymphocytes with normal CSF glucose Fungal- lymphocytes with low CSF glucose
What happens in an epidural hematoma and what should you see on CT
fracture of the skull that severs the middle meningeal artery Lens shaped lesion on Ct
What happens in a subdural hematoma What should you see on CT
Rupture of the bridging veins Blood BENEATH the dura crescent shape
What is the key cell that myelinated axons in the CNS
What is the key cell that myelinated axons in the PNS
What is multiple sclerosis
Autoimmune destruction of CNS myelin and oligodendrocytes HLA-DR2 SIIIN Scanning speech, intention tremor, incontinence, INO, Nystagmus
What is a lacunar stroke and which vessels do they most commonly involve
infarcts in the deep areas of the brain. Mostly in the lenticulostriate vessels off the MCA
Where does intracrebral hemorrhage mostly occur and why
in the basal ganglia due to the lenticulostriate vessels rupturing (micro aneurysms)
Worst headache of life
Subarachnoid hemorrhage usually rupture of saccular (berry) aneurysm usually located in the anterior circle of willis (ACA) Bloody or yellow CSF with tap Only blood at the bottom of the brain
What is Central pontine myelinolysis and how do you get it what is the major presenting case
Focal demyelination of the pons Caused by RAPID iv correction of Hyponatremia (from low to high the pons will die) Presents as Locked in syndrome- acute paralysis-
In GREY MATTER Degenerate neurons in the cortex? Degenerate neurons in the basal ganglia (deeper structure of the brain)?
Dementia Basal ganglia is required for movement so movement problems
Whats the most common disease for dementia? What is it? and grossly brain findings
Alzheimer's dz (degeneration of the GREY matter in the cortex) Slow onset memory loss, disorientation, loss of learned motor skills Diffuse Brain atrophy, narrowing of Gyri/widening of sulk Neuritic plaques (amyloid precursor protein APP with ab amyloid) Neurofibrillary tangles (hyperphosphorylated tau protein)
What are risk factors for Alzheimer's dz?
Deficient Ach ApoE2 (decreases risk) ApoE4 (increases risk) Presenillin -1/2 Neuritic plaques Amyloid precursor protein mess up that causes AB amyloid
What are neurofibrillary tangles, and in which dz are they seen?
Hyperphosphorylated Tau protein seen in Alzheimers Dz
Dementia in elderly due to multiple infarcts of chronic ischemia
Pick'z DZ (Frontotemporal Dementia) it "picks" the frontotemporal
Frontal (behavioral) and Temporal (language) dementia Pick Bodies, ROUND Hyperphosphorylated tau
What is parkinson dz What are the clinical presentations (hint: its a a trap
Degenerative disorder of CNS involving dopamine deficiency neurons in the Substantia viagra Associated with Lewy Body (alpha-synuclein) Tremor (pill rolling) Rigidity (Cogwheel) Akinesia (brady) Posture (instability shuffle gait)
What are lewy bodies composed of? What disorder would you find these
composed of alpha-synuclein found in Parkinson Dz
Difference between lewy body dementia and Parkinson Dz
Lewybody dementia has early onset (parkinson takes a while) cortical lewy body= Ha'lew'cinations
What is the degeneration of gabarnergic (inhibitory) neurons in the brain? Where in the brain is the mess up? Whats the trinucleotide repeat
Huningtons Dz Caudate nucleus GABAnergic (inhibitory) neurons are destroyed CAG (has anticipation so it gets worse with each generation) CAG (C)audate loses (A)ch and (G)aba
What is the striatum and what composes it
Striatum is the basal ganglia which is important in movement. The caudate and the putamen makes it
What is Hydrocephalus and what TRIAD does it present? (wet whack and wobbly) and what usually improves it
Increased CSF resulting in dilated ventricles Urinary incontinence, dementia, gat instability (magnetic feet) Lumbar puncture (LP) relieves pressure
With hydrocephalus you should be thinking the stretching of the _______
Degenerative dz of prion protein most common form is CJD
Creutzfield Jakob dz (CJD)
spongiform encephalopathy rapid dementia Ataxias and startle myoclonus
What is the role of the astrocytes?
Forms the blood brain barrier
What are the tumors that arise from astrocytes? kids/adult
Kids: Pilocytic Astrocytoma Adults: Glioblastoma Multiforme
What is the role of Oligodendrocytes?
Myelinate axons in the CNS
What are the tumors that arise from oligodendrocytes? Kids/adults
Kids: n/a Adults: oligodendroglioma
What is a glioblastoma multiforme? where does it arise
Malignant tumor of the astrocytes in brain Most common malignant CNS tumor in adults Crosses the Corpus callosum- buffterly glioblastoma Psuedopallisading GFAP
What is a meningioma what does it look like on histo?
Benign tumor of the arachnoid cells? Most common benign tumor "Whorl cells"
What is a Schwanomma? which cell type does it arise? What section of brain does it involve /histo
benign tumor of Schwann cells in the PNS Usually located at the cerebellar pontine angle (CPA) and messes with the Cranial Nerve CN8 s100+
Oligodendrogliomas / what cell it arises from / what section of the brain does it involve / histo
Arise from the oligodendrocytes in the white matter (bc they mylelinate-white) fucks with the frontal lobe fried egg appearance calcified tumor
What is the most common CNS Tumor in children and where does it arise (Remember that most kid CNS tumors are below the tentorium)
Pilocytic Astrocytoma Cerebellum Rosenthal fibers GFAP
CNS tumor in kids Neruoectodermal Tumor Former wright rosettes small blue cells
Which cells line the ventricular space in the brain
Malignancy of the ependymal cells commonly arises in 4th ventricle hydrocephalus?
tumor that arises from the remnants of the Rathe's pouch (pituitary) compression of optic chiasm Bitemporal hemianopsia
What is Bitermporal Hemianopsia and what causes it
Compression of the optic chiasm that leads to loss of lateral vision
What is the most common form of vasculitis and who does it usually effect? what are some symptoms? Tx?
Temporal (giant cell) arteritis Granulomatous Vasculitis Older women Headache (temporal), visual disturbances (ophthalmic), jaw claudication Tx-corticosteroids
Same as temporal arteritis (granulomatous vasculitis) But its usually in younger asain females (less than 40) "pulseless dz" Tx=corticosteroids
Necrotizing vasculitis, involving most organs except the lungs usually a Serum Hep. B surface antigen String of pearls
Kawasaki Dz. What is it and who does it affect, and which artery does it mainly fuck up? How do you treat it
Vasculitis affecting asain children less than 4 yrs old. CRASH and Burn Conjunctival injection, Rash, Adenopathy, Strawberry tongue, Hand (foot) edema and fever Coronary Artery IV immunoglobulin and ASPIRIN
Buergers DZ what is it/ the main cause? and whats the clinical finding
Medium vessel vasculitis Caused by heavy smoking Autoamputation of digits
Wegener Granulomatosis We'C'ener Whats the tx
Small vessel vasculitis involves the C's Nasopharynx/lungs/kidney Triad -necrotizing vasculitis, necrotizing granuloma in the lung/upper airway, necrotizing glomerulonephritis C-ANCA tx- Cyclophosphamide
Microscopic Polyangiitis? which organ does it affect? similar to which other small vessel vasculitis except for? how do you treat it?
Small vessel vasculitis affects lung and kidney no granulomas and no nasopharyngeal involvement Tx-Cyclophosphamide P-ANCA
Churg-Strauss? Which organ does it affect? Which small vasculitis is it similar to? how do they differ?
Small vessel vasculitis Necrotizing granulomatous vascuilits w/ eosinophils involves lungs and heart Similar to microscopic polyangiitis (Both have p-ANCA but differ bc it has granulomas and ASTHMA and no peripheral eosinophilia)
HSP (Henoch Schönlein Purpura)? what population is most common? whats the clinical presentation what infection does it usually follow
Small vessel vasculitis due to IgA immune complex deposition (IgA nephropathy) most common in children Palpable purpura on BUTT/LEGS Follows Upper Respiratory Infection
What is the defined limits of Hypertension and risk factors
BP >140/90 age,race, obesity, high salt diet
What is atherosclerosis? which size vessels does it effect? what are the 4 main arteries it hits (in order of occurrence) how much occlusion do you need to have symptoms
A buildup of cholesterol plaque in medium/large muscular arteries Abdominal Aorta > coronary a.> popliteal A. > carotid greater than 70%
What is the progression of Atherosclerosis
1. endothelial cell fuck up 2. macrophage and LDL accumulation 3.Foam cell formation 4. Fatty streaks 5. Fibrous plaque
What are the two types of ArteriOLOsclerosis
Hyaline:Vascular thickening of vessel wall with protein caused by Hypertension and diabetes Hyperplastic: Onion Skinning caused by sever HTN
What causes Hyaline ArteriOLOsclerosis What does it lead to?
HTN and Diabetes HTN increased BP forces protein into the vessel wall Diabetes- Causes vessel wall to be leaky so protein leaks in leads to ischemia and glomerular scarring
What causes Hyperplastic AteriOLOsclerosis
Thickening of vessel wall due to hyperplasia of smooth muscle due to malignant HTN
Where do you see fibrinoid necrosis (beads on string)
Whats an Aortic Dissection What disorders are prone for Dissections Most common Cause of death
When a rip in the INTIMA of a vessel causes blood to penetrate and create a lumen between intima and media Literally rips through and dissects the two layers due to Pre-existing weakens of the media (HTN) Connective tissue disorders (Marfan Syndrome) Cardiac tamponade
Thoracic Aneurysm What dz most commonly leads to it whats the most common clinical presentatoin
Balloon like dilation of the aorta. must have weakness in the wall Tertiary syphilis - caused by endarteritis of vaso casorum (prevents nutrients to the wall of vessels so it atrophies) Pulsatile abdominal mass
Chest pain that arises with exertion or stress is ____ What dz commonly leads to it Whats the most common presentatoin
atherosclerosis- not enough blood getting to the heart so it becomes hypoxic/ischemic
Chest pain that radiates to left arm or jaw -St depression Tx- rest or Nitroglycerin
Chest pain that occurs at rest is ____ What causes it? Tx?
Unstable angina Rupture of atherosclerotic plaque with thrombosis and incomplete occlusion of the coronary artery -Nitroglycerin high risk of MI
Vasospasm of the coronary artery? Tx
Prinzmetal angina tx-CCB's or Nitrates
Difference between myocardial infarct (MI) and unstable angina
MI has Thrombosis of a Plaque with COMPLE occlusion. also has IRREVERSIBLE damage to myocytes
Which chamber of the Heart does MI mostly occur? Which coronary artery usually gets occluded
LEFT VENTRICLE 1-Left anterior descending (LAD) anterior wall and atrial septum necrosis 2. Right coronary artery-poserior wall of heart
ST elevation MI (STEMI) What type of infarct thickness?
Transmural Full thickness
non ST elevation MI (NSTEMI) thickness?
Which enzymes are indicative of an MI
TROPONIN rises at 2-4hrs peaks at 24 hrs elevated for a week CK-MB rises and goes down quickly can be used to determine multiple infarcts
Which cardiac enzyme is used to determine multiple infarcts
CK-MB because it rises and galls quicker than TROPONIN
Tx for Myocardial infarction
Aspirin/Heparin (to prevent further clotting) Supp. O2 Nitroglycerin Beta Blockers
What is the progression of an MI (days weeks months)
1 day / 1 week / 1 month coagulative necrosis (dead cells) / Neutrophils and macrophages / granulation tissue and scar
Type of pericarditis that occurs 6 weeks after an infarct due to autoantibodies against the pericardium
Whats congestive heart failure mainstay treatment?
When the heart fails to pump appropriately (usually backs into the lungs) Tx-ace inhibitors
Heart failure cells found in lungs with pulmonary edema
Whats the most common congenital heart defect and what syndrome is it associated with
Ventricular septal defect (VSD) associated with FETAL ALCOHOL SYNDROME
What is the mnemonic for left to right shunt yes right to left?
(R)ight to (L)eft shunts are eaRLy cyanosis (L)eft to (R)ight occur LateR cyanosis
What is atrial septum defect? what defect causes this
defect in the septum between atriums Osmium secundum defects
Holocystolic machine like murmur cyanosis of lower extremities How do you treat this What disorder is it associated with
Patent ductus arteriousus PDA failure of ductus arterioles to close cyanosis of lower extremities Tx-ENDomethacin ends PDA Congenital rubella
Tetralogy of Fallot
R-->L shunt most common cause of eaRLy cyanosis (fixed with squatting) Pulmonary stenosis Boot shaped heart (hypertrophy) Overriding aorta/VSD
Transposition of the Great vessels? What dz is it associated with
Failure of the aorticopulmonary system to spiral (they swap places) Maternal diabets
What is rheumatic fever? What is it usually caused by?
occurs 2-3 weeks after strep throat (alpha-beta hemolytic streptococci) M- protein JONES criteria which is joints, heart problems, nodules, erythema marginatum, s-chorea arthritis, pan(all layers)carditis (mitral valve), subQ nodules, rash, rapid movement
Jones criteria whats it used to diagnosis
joints, heart problems, nodules, erythema marginatum, s-chorea arthritis, myocarditis (mitral valve), subQ nodules, rash, rapid movement
Aortic Valve Stenosis how do you get it? What cardiopathy and other symptoms does it lead to?
Narrowing of the aortic valve Systolic ejection click followed by crescendo- decrescendo murmur "wear and tear of valve" -presents in late adult hood or when you have a bicuspid valve instead of (tri) leads to Left ventricular hypertrophy SAD Scope, Angina, and Dyspnea on exertion
Aortic Regurgitation why does it happen?
"blowing murmur" Back flow of blood from aorta into LV during diastole Aortic root DILATION or valve problems Hyperdynamic circulation (bounding pulse, pulsating nail bed, head bobbing)
What is hyper dynamic circulation and what causes it?
Seen in aortic regurgitation Bounding pulse, pulsating nail bed, head bobbing the regurg increases the volume of the next stroke in LV so it keeps adding and adding pressure
Mitral valve prolapse
ballooning of the mitral valve into left atrium during systole Myxoid degeneration of the valve (floppy) *mid systolic click* like a parachute
Mitral Stenosis what happens to the atrium
Narrowing of the mitral valve, usually due to rheumatic valve dz Opening snap followed by a rumble LA overload- pulmonary congestion (edema)
Which organism causes Endocarditis (low virulence)
S viridians most common cause of endocarditis, infects previously damaged valves results in small vegetations that don't destroy valves
Which organism is the most common cause of (acute) Endocarditis in IV drug users and which valve is involved
S. Aureus (acute) Large vegetations on normal valves Most commonly Tricuspid
Which organism causes Endocarditis of prosthetic valves?
Which organism causes Endocarditis with underlying colorectal cancer
Endocarditis with Negative Blood cultures
HACEK Haemophilus, actinobacilus(aggregatibacter, Cardiobacterium, Eikenella, Kingella)
Clinical features of endocarditis
Fever, murmur, Janeway lesions(painless on palm or sole), Osler (ouch) nodes (painful on fingers or toes)
endocarditis with nodules on both sides of the valve And what is it associated with
Libman-Sacks Endocarditis SLE mitral valve
Dilated Cardiomyopathy (most common cardiomyopathy) What causes it tx-
Dilation of all 4 chambers systolic dysfunction (dilated so it can't contract properly), valve regurgitation ABCCCD + p alcohol abuse, Beri beri, COXSACKE, cocaine use, Chagas, Doxorubicin toxicity and pregnancy Transplant
Hypertrophic Cardiomyopathy whats a huge problem with this
Hypertrophy of left ventricle commonly due to genetic mutations in Sarcomere protein Decreased cardiac output due to the heart being so tight. (it can't dilate to get blood in) Can lead to SUDDEN DEATH due to ventricular arrhythmia myofibrillar disarray
Restrictive cardiomyopathy what are the causes
Decreased compliance of ventricles (won't dilate so you have a diastolic problems sarcoidosis, fibrosis, endocardial fibroelastosis (thick fibroelastic tissue in endocardium of young children), hematochromatosis LOFFLER SYNDROME- endomyocardial fibrosis with a prominent eosinophilic infiltrate
Loffler syndrome and does it lead to
endomyocardial fibrosis with a prominent eosinophilic infiltrate leads to restrictive cardiomyopathy
Myxomas were does it usually occur (which valve)
Most common primary cardiac tumor in ADULTS Usually occurs in the left atrium and causes syncope described as "Ball valve" obstruction
most common primary cardiac tumor in CHILDREN associated with tuberous sclerosis
what is primary hemostasis
injury to a blood vessel that results in a PLATELET PLUG (stabilized by secondary hemostasis)
What is secondary hemostasis
Stabilization of the platelet plug via coagulation cascade
Steps of thrombogenisis
1)Endothelial damage= vasoconstriction 2)Exposure: vWF is exposed to collagen and binds 3)Adhesion: Platelets bind to vWF via Gp1b (conformational change) platelets release ADP and Thromboxane 4a)ADP helps platelets adhere to endothelium via increased Gp2b/3a receptors 4b)platelet aggregation via FIBRINOGEN between Gp2b/3a receptors
Where does vWF come from?
Weibel-palade bodies of the endothelial cells and Alpha-granules of platelets
Clinical signs of Primary hemostasis fuck up
Mucosal and skin bleeding (nose -EPISTAXIS-, gi, menstrual)) bruising, petechia, purpura
Idiopathic Thrombocytopenia Purpura (ITP) what clinical values will you see Tx?
Autoimmune production of IgG antibodies against platelet antigens low platelet count, increased megakaryocytic tx-corticosteroids, ivig (the spleen produces the antibodies and also destroys them. so ivig will distract the spleen to give the bodys platelets a chance to recover), splenectomy
Microangiopathic hemolytic anemia
Small blood vessels get a platelet thrombus that shears any passing RBCs Shcistocytes (helmet cells)
Thrombotic thrombocytopenia purpura (TTP) tx=
platelet aggregation that leads to thrombocytopenia (purport from lack of platelets) Deficiency of ADAMTS13 (which breaks down vWF) so you have to much vWF which leads to increased platelet aggregation tx-plasmapharesis, steroids
Thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure seen in children after Etec infection caused by Shiga like toxin
Bernard-Soulier syndrome? whats the defect in?
a defect in platelet plug formation due to decrease in Gp1b defect in platelet-to-vWF adhesion increase bleeding time
genetic deficiency in Gp2b/3a platelet aggregation is impaired ( G2pb/3a is what connects platelet to platelet via fibrinogen
vWF disease tx-
deficient in vWF tx- desmopressin
Vit. K deficiencey
Decrease in synthesis of factors 2,7,9,10,C,S 7 having the shortest half-life
inhibits vit K synthesis via inhabiting epoxide reductase
Heparin induced Thrombocytopenia (HIT)
when you develop IgG antibodies against Heparin-bound platelet factor 4 (PF4) the antibodies activate platelets--> thrombosis and thrombocytopenia elsewhere
Disseminated inter vascular coagulation (DIC) whats the best screening test?
Secondary to other dz pathologic activation of coagulation cascade widespread micro thrombi that leads to ischemia and infarction Consumption of all these platelets leads to bleeding everywhere else (especially IV and mucosal sites) test- Elevated D dimers (when you split fibrin it produces D dimers)
What blocks activation of plasminogen
What two characteristics would you see in a thrombosis
Lines of zahn attachment to vessel wall
Vitamin B12 or folate deficiency leads to elevated ________
TetrahydroFOLATE to methionine
THF--> gives off methyl to Vit. B12---> gives methyl to Homocysteine ----> methionine
Whats the role of Protein C or S
Inactivate factors V and VIII in coag cascade
whats the deal with factor V leiden
Resistant to degradation/inactivation by Protein C
Whats are the anemia subtypes (based off of MCV) mean corpuscular volume (size of red blood cell)
Microcytic MCV 100
Role of ferroportin Role of Transferrin Role of Ferritin
Transfers iron into the blood Delivers iron to liver and bone marrow macrophages Iron Storage
Why do you get anemia of chronic dz?
With chronic dz, you get prolonged inflammation. and in order to stop whatever is causing the sickness, the body increases hepcidin (which fucks up ferroportin and prevents release of iron from ferritin ) which decreases iron transport ----> iron deficiency ---> anemia ferritin goes up/ TIBC goes down Serum iron goes down
What does hepcidin do
Prevents release of iron from storage sites to deprive any infection of iron and kill it off
what are some of the causes
Defect in protoporphyrin synthesis --> defect in Hb. due to X-linked defect in ALA synthase
defect in protoporphyrin leads to iron getting trapped in mitochondria of erythroblasts
congenitcal (ALA synthase), lead poisoning, alcoholism, or B6 Deficiency (pyridoxine)
what attaches Protoporphyrin to Iron (to make heme)
where does this happen
when protoporhyin synthesis is messed up so iron gets loaded into mitochondria.
This iron has nothing to bind to so its trapped there. These iron-laden mitochondrias form rings around the nucleus
Decrease in synthesis of Globulin chains
(leads to microctyic anemia)
4 allele deletion
3 allele deletion
2 and 1 allele deletion
Normally you have 4 alpha alleles
Defect in A-globin deletion
4 allele-no alpha globin, excess gamma globin, (makes gamma4 -Hb Barts) Hydrops fetalis
3 allele- very little alpha globin, Excess ß-globin (HbH)
2/1 not clinicilaly severe
whats the significance of cis vs trans deletions in alpha-thalassemia
cis is when 2 alpha alleles are knocked out on the same chromosome. this can lead to to severe thalasemia in offspring (Prevalent in Asains)
Trans isnt that bad (African population)
ß-Thalassemia (2 beta genes)
Minor (ß/ß+) (normal/diminished)
Major (ß°/ß°) both B are wiped out
minor-asymptomatic with Increase in HbA2
Absent Beta chain, target cells,
massive erythroid hyperplasia- expansion of hematopoiesis into marrow of Skull and facial bones (crew cut and chipmunk like face)
extramedulary hematopoiesis- liver and spleen starts to make it (hepatosplenomegaly)
Risk of Parvovirus B19- aplastic crisis
MCV? what deficiencies cause it? why do the deficiencies lead to it
Folate or Vit. B12 deficiency
(1 less division so theyre macro) due to mess up of DNA precursors
whats the role of folate and Vit B12 in synthesis of DNA (flow chart)
Tetrahydrofolate has a methyl and in order for it to make DNA it has to give that methyl to Vit. B 12
Vit B12 then gives that methyl to Homocystiene.
Homocystiene + methyl = Methionine
Where is folate absorbed?
what casuses its deficiency
Clinical findings of deficiency
-In the Jejunum
-Poor Diet (alcoholics,elderly), Increased demand (preggos, cancer, hemolytic anemia), Drugs methotrexate
-Megaloblastic anemia (macrocytic RBCs, Hypersegmented Neutrophils), Glossitis
-Decreased serum folate(duh),
Increased Homocysteine( piles up because folate doesnt pass Methyl to vit.b12 -->so vit b12 cant change homocysteine to methionine
Methylmalonic acid is Normal
Vit. B12 (Cobalamin)
How is it absorbed/where
What causes its deficiency (alot)
Clinical and lab findings
First needs to be cleaved by pancreatic enzymes
Then, it binds to Intrinsic Factor (IF) to be absorbed in the Ileum. Large hepatic stores so it takes a long time to develop deficiency.
-caused by insufficient uptake (Vegan), malabsorption (Crohn dz), Pernicious anemia (Autoimmune destruction of parietal cells- cant make IF)
Diphyllobothrium Latum (fish tapeworm)
-Macrocytic anemia with Hypersegmented neutrophils, Glossitis
-Subacute Combined Degeneration of Spinal Cord -B12 converts methylmalonic acid --> Succinyl Coa. so without B12 you get a shit tone of mma which is toxic to myelin
Autoimmune destruction of Parietal cells.
This leads to a deficiency of Intrinsic Factor (IF)
Which means you cant absorb Vit B12
What are the 2 major processes that Vit B12 are invovled in?
-In the synthesis of DNA, by accepting methyl from Tetrahydrofolate, then giving it to Homocysteine
-Converts Methylmalonic acid ----> Succinyl CoA myelin synthesis
too much methylmalonic acid is toxic to myelin
what does the reticulocyte count look like?
-Increased reticulocyte count/percentage (falsely elevated) due to destruction of RBCs
You must correct it tho.
In normocytic anemia, what are the perameters for when you correct the reticulocyte count?
Whats the equation
>3% indicates good response by bone marrow; suggests peripheral destruction
<3% indicates bad response by bone marrow; suggests underprodcution
Reticulocyte count x (Hematocrit/45)
in the example it would be a bone marrow problem
Which Anemia does it cause
What are clinical findings
-Extravascular destuction occurs from macrophages in spleen
-Anemia with Splenomegaly, Jaundice due to unconjugated bilirubin (increased risk for gallstones), marrow hyperplasia with corrected reticulocount >3%
remember that when hemoglobin is broken down, the protoporhyrin of heme gets turned into Unconjugated billirubin
What type of anemia does it cause
-Destruction of Hemoglobin in the blood vessel. Haptoglobin (binds to free Hb and brings it back to spleen)
Hemoglobinemia, Hemoglobinuria, Hemosiderinuria
Binds free hemoglobin (Hb) and brings it back to spleen.
levels of haptoglobin are decreased in intravascular hemolysis bc they get used up
how is it diagnosed
Extravascular hemolysis due to defect in RBC membrane (ankyrin, band 3, spectrin are protein fuckups)
Small round RBC with no central pallor (premature removal by spleen)
Increased MCHC (mean corpuscular hemoglobin concentration) only dz with this
-Splenomegaly, Aplastic crisis (ParvoVirus B19 infection)
-osmotic fragility test
Sickle Cell Anemia
whats the mutation?
what causes the sickling
What protects against the sickling (tx)
Auto Recesive mutation in the ß gene (glutamic acid with valine)
-Stressors such as Low O2, high altitude, acidosis, dehydration
-HbF(fetal), give hydroxyurea to increase HbF
'-Aplastic crisis (parvovirus B19),
Painful crisis: dactylitis (sausage fingers), acute chest syndrome, avascular necrosis
Autosplenectomy (howell jolly bodies)- due to infarct of the spleen. increases risk of infection S. pneumonia
whats the mutation
Auto Recessive mutation in ß Chain
Glutamic acid is replaced by Lysine
Paroxysmal nocturnal hemoglobinuria (PNH)
why does it happen?
what does it lead to
aquired dsyfunciton of GPI via hematopoietic stem cell
(anchors decay-accelerating factor -DAF CD55- that protects RBC from complement activation)
at night we breath slower leading to respiratory acidosis --> activation of compliment (intravascular hemolysis) which will fuck up these RBCs since theyre predisposed already
-leads hemolytic anemia (duh), pancytopenia, thrombosis
10% of pts develops AML
-tx eculizumab (compliment inactivator)
whats its function
what causes oxidative stres
what cells does this produce?
X-linked Recessive d.o -->reduced half life of G6PD
(increases RBCs succeptible to oxidative stress)
G6PD helps create NADPH. NADPH helps produce glutathione which protects against oxidative stress
-Infections, Fava Beans
Heinz bodies & Bite cells
Back Pain from all the released Hb(nephrotoxic)
Immune hemolytic Anemia
What are the different types
what are they associated with
Warm IgG: EXTRAVASCULAR chronic anemia due to IgG binding to RBC and removing membrane (results in spherocytes). Associated with SLE and CLL (Methyldopa) / (Warm weather is GREAT)
Cold IgM: Acute anemia triggered by cold. Associated with CLL, Mycoplasma pneumonia, Infectious Myonucleosis. (Cold weather is MMMiserable)
What is the Coombs test?
Direct. vs indirect
direct- do i have cells already bound by IgG? you give them anti- IgG. so if the answer is yes, the RBCs wil agglutinate and percepitate
Indirect- Does the pt have antibodies in their serum? normal RBCs added to patients serum. if serum has the antibodies, the RBCs agglutinate when Coombs is added
Whats the CD for hematopoeitic stem cells?
Give the lineage of everything that it can produce
What are some causes of Neutropenia
What are causes of Lymphopenia
Immunodeficiency: HIV, SCID, SLE, sepsis
High levels of cortisol (or corticosteroids)-these cause apoptosis
Radiation (lmyphocytes die quickest)
Whats the anatomy of lymph node
What areas are the B and T cells located
B cells are in the cortex (follicles)
T cells are the in the Paracortex (swells with viral infection)
What are the markers for Lymphoblasts in the blood?
TdT+ (marker of pre T and pre B)
CD10,19, 20 (marker of pre B)
Tell me about ALL (acute lymphoblastic Leukemia)
whats the good translocation
Most frequently in childeren
Highly associated with Down syndrome (after age of 5)
T(12;21) has good prognosis
Subdivided into T-ALL and B-ALL
**acute is always immature
T-ALL what physical finding should give it away
T should make you think of Thymic (Mediastinal mass)
AML (Acute Myeloblastic leukemia)
whats the classic translocation (also known as APL-acute promyelocytic leukemia). and what does this trans do?
what systemic problem can AML lead to? and how do you treat it?
Myeloperoxidase (+) ->these aggregate to form Auer Rods
APL- T(15;17) fucks up the retinoic acid receptor ->the cells cant mature
can lead to DIC (treat with ATRA-causes blasts to mature)
under AML, if the leukemia is specifically monocytes, what should you think of
lack Myeloperoxidase//heavily infiltrates the Gums
Associated with Downs syndrome before 5
whats the deal with CLL
who does it affect, what are the cell markers
what type of cells will histo show
what can CLL transform into?
Usually in older adults
proliferation of naive B cells (CD5,20)
Diffuse Large B-cell Lymphoma (DLBCL)
Hairy Cell Leukemia
what does it stain positive for?
proliferation of Mature B-cells
stains positive for TRAp
massive Splenomegaly (red pulp) / dry tap on bone marrow aspiration
CML (chronic myelogenous leukemia)
whats the translocation
how do you treat it
what can it transform to?
increase of mature granulocyte (mostly basophils) LAP (-)
Philadelphia chromosome t(9;22)
BCR-ABL (increases tyrosine kinase activity)
To treat, you gotta inhibit tyrosine kinase - Imatinib
can transform into Acute Leukemia
what is messed up(mutation) that causes it
proliferation of mature myeloid cells (especially RBCs) EPO is decreased
JAK2 kinase mutaiton
-blurry vision, Increased risk of thrombosis (Budd chiari), flushed face, itching after bathing (mast cells release histamine)
tx-phlebotomy (get rid of some of that blood)
2nd tx is hydroxyurea
2° Polycythemia (reactive)
Increased EPO from either lung dz (low O2)
or Tumor that produces EPO (renal cell carcinoma)
proliferative disorder of myeloids (specifically Platelets)
shit ton of platelets - either bleeding or thrombosis from lack of function or overfunctioning platelets
what does it lead to
what cells does it make
myeloproliferative disorder (specifically Megakaryocytes)
JAK2 kinase mutation
marrow fibrosis - so the marrow cant make new RBCs which means you get extramedullat hematopoeisis in the spleen (splenomegaly)
What are the subcategories
Tumor that arises from lymphocyte
Hodgkin lymphoma &
Non-Hodgkin Lym : Burkitt, DLBCL, Mantle,
what is it/clinical signs
neoplastic Bcells (CD20) that make small follicle like nodules
Painless LAD (waxing and waning)
T(14;18) - switches heavy chain IG with BCL-2 (inhibits apoptosis) so you get over exp resion of BCL-2
What does BCL-2 do
cell marker that inhibits apoptosis
Mantle Cell Lymphoma
whats the translocation
neoplastic B cells that expand the mantle zone
t(11;14) cyclin D and IG Heavy chain
overexpression of cyclin D causes cell to go from G1 to S phase
What does Cyclin D do?
causes cell to go from G1 to S phase in cell cycle
What is it associated with
what are the 2 different forms
Translocation/ what does histo look like
neoplastic B cell prolif (CD20)
associated with EBV
-Endemic African: Jaw lesion // Sporadic: abdomen
t(8;14) : C-myc (promotes cell growth)
Starry Sky Appearance
Diffuse Large B-cell Lymphoma (DLBCL)
most common form of NHL
large nodes or extranodal mass
what cell do you see on histo
Reed-sternberg cells (owl eyes) CD15/30
you get B-symptoms: fever, night sweats, weight loss
what are some sypmtoms (CRAB)
which IG's are most spiked
Malignant proliferation of plasma cells in marrow
Fried egg appearance
HyperCalcemia, Renal involvment, Anemia, Bone lesion (lytic- punched out)
M Protein spike (increase in Monoclonal immunoglobin (IG G/A)
Increased risk of infection, Rouleaux formation (stacked RBCs), Ig light chains in urine
Monoclonal gammaopathy of undetermined significance (MGUS)
When you get an M spike but you dont have any of the CRAB symptoms of Multiple Myeloma
M spike of IgM with no CRAB. hyperviscosity syndrome like blurred vision and raynaud
Langerhan cell Histiocytosis
what would histo show
proliferative disorder of (langerhan )dendritic cells found in skin. cells express s100
-Birbeck granules (Tennis racket)
-skin rash/ lytic bone lesion
what artery does horse shoe kidneys get stuck on?
inferior mesenteric artery
Bilateral Enlarged kidneys due to cysts in renal cortex and medulla
Autosomal Recessive PKD
what are the clinical signs
usually presents in infants.
Renal failure, HTN, Hepatic fibrosis
Autosomal Dominant PKD
where is the mutation?
How do they present?
What other d.o's are they associated with?
The mutation is in PKD1(85%) or PKD2
-present with Flank pain, hematuria, HTN, Renal failure(Duh)
-Berry aneurysm, hepatic cysts, mitral valve prolapse
(cysts in the liver, brain, and kidney)
Medullary cystic Kidney Dz
what will the kidneys look like?
inherited defect of Cysts in the collecting ducts
Increase in urine BUN and Creatinine
Acute Renal Failure
Abrupt decline in renal function measured by Azotemia (Increase in BUN and Creatinine
-Decrease in Renal BLood Flow
-Acute Tubular Necrosis
-Due to decrease in Renal blood flow (Hypotension)
-Increased BUN/Creatinine Ratio
(BUN is absorbed, creatinine is not)
Hypotension so the kidney is tryna hold onto whatever it can to conserve volume
BUN/Creatinine ration >20
Acute Tubular Necrosis
(intra renal failure)
Whats seen in the urine casts?
what are serum and lab findings
What are the two ways to get it?
Injury and necrosis of Tubular epithelial cells. These necrotic cells plug the tubule which obstructs and Decreases GFR
-Muddy brown casts
-bc the epithelial cells are fucked you get messed up (decreased) resorption of:
BUN which means BUN:CR is <15
Na which means FeNA >2%
Inability to concentrate urine --- Osmalitly<200
-Ischemic & Neprotoxic
Ischemic Acute Tubular Necrosis (ATN)
which parts are most often fucked up
Decreased Blood supply results in necrosis of tubules
-PCT(proximal tubule) and Thick ascneding limb
Nephrotoxic Acute Tubular Necrosis (ATN)
What parts get fucked up?
what agents are nephrotoxic?
Necrosis of tubule cells due to toxic agents
-only PCT (proximal tubule)
-Aminoglycosides, heavy metals, Myoglobinuria (Crush injury), Ethylne Glycol, Radio contrast
Acute Interstitial Neprhitis
which drugs cause this?
what is a giveaway if you see it in the urine
what can it lead to?
Intra renal ARF (acute renal failure)
Drug induced hypersensitivity reaction
-NSAIDs, Penicillins, Diuretics
-Eosinophils in the urine
-can lead to Renal Papillary Necrosis
Renal Papillary Necrosis
-causes (SAAD Papa)
Necrosis of Renal papillae
Gross Hematuria and flank pain
-causes: Sickle cell, Acute pyleonephritis, Analgesics(Nsaids), Diabetes Mellitus
Whats the main hallmark of this?
what all lost becasue of it
List all 6 dz that leads to this
- PrOteinuria (>3.5g/day). due to any damage of the GFR barrier
Loss of Albumin which causes EDEMA
Loss of immunoglobulins --> increased infections
Loss of Antithrombin III(ATIII) --> Hypercoag
Hyperlipidemia- frothy urine
-Minimal Change Dz, Focal segmental glomerulosclerosis (effacement of podocytes)
-Membranous Nephropathy, MPGN (deposition of immune complexes)
-Diabetic Glomerulonephropathy, Amyloidosis
Minimal Change Dz (MCD)
who gets it
what causes this which can be seen on EM
which protein do you lose?
most common cause of NephrOtic syndrome in kids
-effacement of foot processess (podocytes) due to cytokines
you only lose albumin
Focal Segmental Glomerulosclerosis
Who usually gets this?
What is it associated with
what what it look like on histo
whats special about the treatment and what can it progress to
-most common cause of NephrOtic syndrome in Hispanics and Blacks
-HIV, Heroine, and Sickle cell
-Focal (not all glomeruli) Segmental (only part of affected glomeruli) Slcerosis (deposition of pink collagen)
-poor response to steriods and can progress to chronic renal failure
who gets it
whats it associated with
whats it look like on histo due to?
Most common cause of NephrOtic syndrome in Caucasian adults
-Hep B/C, Solid Tumors, SLE
Very thick membranes due to immune complex depositions
-Spike and Dome on EM
what does it look like on stain
divided into two types. explain them and what they are associated with
Thickening of the glomerular membrane due to deposits of Immune complexes
Tram Track appearance because the membrane gets split by the mesangial cells
-Type 1: Subendothelial deposits. Hep B/C
-Type 2: Basement Membrane deposits. C3 Nephritic factor (activates complement by stablizing C3 convertase)
Where are the immune deposits in MPGN (membranous proliferative glomerulonephritis) and Membranous nephropathy
MPGN type 1: Subendothelia
MPGN type 2: basement membrane
What does the diabetes do? how to treat it
what kind of nodules will you see?
cause of NephrOtic syndrome
High blood sugar leads to Nonezymatic glycosylation of GBM
leads to leaky and thickening
also increase in GFR due to constriction of efferent arteries (can be treated with Ace inhibitors
what will stain show?
Cause of NephrOtic syndrome
Kidney is the most common organ of Amyloid deposition
Congo Red stain shows apple-green birefiringence
whats the hallmark finding
what causes the finding
What are the different types
-Glomerular Inflammation and bleeding that leads to hematuria and RBC casts in urine
limited proteinuria (<3.5g/day)
-deposition of immune complex triggers inflammation
-Types: Post Strep Glomerulonephritis, Rapidly progressive glomerulonephritis (Crescentic), IgA nephropathy
Post Strep GlomeruloNephritis (PSGN)
when does it occur and the virulence factor
-whats it look like on histo
how do you treat it?
Main cause of NephrItic Syndrome
-occurs after group A, ß hemolytic strep infection of skin or throat
-Periorbital Edema, Cola Urine, Hypertension
-"Lumpy bumpy Hump" GRANULAR on Basement membrane
-it usually resolves on its own
Rapidly Progressive Glomerulonephritis (Crescentic)
what are the crescents made of?
What will the Immunoflorescence look like?
A cause of NephrItic syndrome that progresses to renal failure in weeks to months
Crescents in the glomerulus
-crescents consist of Fibrin and plasma proteins
Linear: Antibodies to basement membrane = Goodpasture syndrome
when do you usually get it?
Cause of NephrItic Syndrome
IgA immune complex deposition in Mesangium of Glomeruli
Concurrently with Respiratory or GI Tract infection (the IgA gets secreted by mucosal linings)
cause of NephrItic syndrome
inherited (X-linked) defect in Type 4 collagen
-thinning and slpitting of the GBM
Eye problems, ear problems kidney problmes,
cant see, cant pee, cant hear a bee
Urinary Tract infection
whos at higher risk
whats in the lab findings
which bacteria cause these?
what if you have a negative culture
Infection of urethra, bladder (cystitis), or kidney
most commonly ascending infection, women are more risk due to shorter urethra
+ Leukocyte esterase, + nitrites,
urine culture >100k
-E Coli > Staph saprophyticus > Klebsiella > Proteus mirabilis (pee has ammonia scent)
-negative culture suggests Neisseria gonorrhoaeae / Chlamydia
how does it present?
whats in the urine
Infection of the kidney (usually due to ascending infection)
-fever, flank pain (Costovertebral angle)
WBC casts in urine
which abnormality usually causes this
what does this look similiar to/mimic on histo
when you get acute pyelonpehritis a bunch and you get atrophy and fibrosis of the tubules
-vesicoureteral reflux (relfux back into the ureters up to the kidney)
cortical scarring with blunted calyx
what kind of stones are there and shape/associations/tx
Colicky pain with unilateral flank tenderness, hematuria
-Calcium oxylate (most common): envelope,chrons dz, tx=HCTZ
-Amonium magnesium phosphate: coffin, ureas(+) organisms: Proteus or Klebsiella tx=surgically remove (Staghorn)
-Uric acid: rhomboid, acidic ph/hot climate/gout(duh), tx=Allopurinol
-Cysteine: seen in children, genetic defect where you dont reabsorb Cysteine, Staghorn
Renal Cell Carcinoma
what can it be associated with
what does it look like grossly
what mutation leads to this and which chromosome is it on
-hematuria, palpable mass, flank pain
-associated with paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP, renin)
-golden yellow mass + clear cell
Loss of von hippel-lindau (VHL) suppresor gene on Chromosome 3
how does pt present
what syndrome can this be a part of?
Most common kidney tumor in kids
-Large palpable unilateral flank mass, hematuria, HTN
-Loss of function of WT1 or WT2
WAGR- Wilms, Aniridia(no iris), GU malformations, mental Retardation
main cause of rhinitis
what is a major consequence it can lead to
when a child has nasal polyps what should you be thinking?
ASA (asprin) intolerant asthma
main cause of epiglottitis
what does the sputum look like?
3 types of pneumonia?
Infection of lung parenchyma
-yellow green or rusty colored sputum
-Lobar, Bronchopneumonia, Interstitial
which are the two most common causes
consolidation of an entire lobe
S. Pnuemonia (95%) & Klebsiella Pneumoniae
which bacteria causes this
scattered patchy pneumonia cetered around the bronchioles
-S. A, H. influ, S. pneumonia, klebsiella
interstitial (atypical) pneumonia
why is it called Walking Pneumonia
What causes it
diffuse interstitial infiltrates
-has very mild symptoms
-Mycoplasma pneumonia (military recruits or college kid), Chlamydia Pnuemonia, RSV (infants) , CMV (post transplant)
whats the PPD
inhalation of Mycobacterium Tuberculosis
-caseating necrosis of lower lobe
-Ghon complex (fibrosis and calcification)
Secondary- reactivation of TB due to AIDs (APEX) of lung. CASEATING granulomas
whats the spirometry readings
obstruction of getting air OUT of the lung
ForcedVC (down), FExpiratoryV1(down-down)
TLC(up) due to lung trapping of air
-Chronic Bronchitis, Emphysema, Asthma, Bronchiectasis
how does one get it
Whats the Reid index and whats the value for CB
How do they present
whats a bad thing this can lead to
Hyperplasia of mucus secreted glands as a result of smoking
Reid index is the thickness of mucosal gland layer to the thickness of wall btwn epithelium and cartilage. For CB its >50%
-presents with Productive Cough, Cyanosis
-Cor Pulmonale (hypoxia leads to vasoconstriction to area and shunting to other areas in lung--> failure of right heart)
what imbalnace/deficiency causes this?
most common cause of this?
what are the two types? which lobes are they associated with?
whats a nickname for this?
Destruction of alveolar sacs
loss of elastic fibers, increased compliance, "Shopping bag', AIrway collapse
Lack of Alpha 1 AntiTrypsin (A1AT)
-SMOKING (duh bruh)
Centriacinar (smoking-upper lobes)
Panacinar (A1AT deficiency- lower lobes)
-PINK PUFFER (barrel chest)
Reversible Bronchospasm most often due to allergic stimulus
IgE Hypersensitiviy type 1 mediated
4 - IG class switching
5 - calls in eosinophils
10 - stimulates th2 T cells
what causes it?
Permanant dilation of the bronchioles and bronchi
loss of tone leads to air trapping
(think of blowing throught a big pipe)
-necrotizing granulation of airway wall
Restrictive respiratory DZ
whats the FEV:FVC ratio?
Restricted filling of the lung mostly due to FIBROSIS
Ratio is INCREASED >80%
Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis
what does lung look like?
repeated wound healing with collagen deposition
Honeycomb lung appearance
Interstitial fibrosis due to occupational exposure
coal worker, silicosis, abestosis
coal workers pneumoconioses
whats caplan syndrome?
Restricitve lung dz (fibrosis)
macrophages laden with carbon lead to inflammation and fibrosis
caplan: rheumatoid arthritis and penumonconioses
Antrhacosis: carbon in the lung thats assymptomatic
how does it affect macrophages?
whats special solely about this pneumocon.?
what part of lung does it affect? (roof and base)
Restrictive lung dz (pneumoconioses)
-it impairs the phagolysosome
-its the only wone that increases chance of TB
"silica and coal are on the base, but affect the roof"
restrictive lung dz (pneumoncon.)
exposure to beryllium in aerospace
where does it affect the lung
what do you look for to confirm diagnosis
restrictive lung dz (pneumocon)
Associated w/ shipbuilding, roofing, plumbing.
-asbestos (ferrunginous) bodies: golden brown rods
which type of lesion and where will you find them
who gets it?
what else type of cell can you see in this histo?
what values are elevated?
why does this cause hypercalcemia?
Restrictive lung dz
"noncasesating granuloma" in multiple organs (speccifically lung and hilar lymp nodes)
African american femal under 40yrs old
-elevated ACE levels, CD4/8 ratio
-due to incr. 1Alpha-hydroxylase vit D activation in macrophages
Small cell carcinoma
who gets it, where is it located, what does it produce
poorly differentiated small cells
Male smokers, Centrally,
may produce ACTH or antibodies against PRESYNAPTIC Ca+2 channels (lambert-eaton)
Squamos cell carcinoma
Whats the big clue on histo
where is it? what symdrome?
Keratin pearls and Intercelluar bridging
-produces PTHrP (hyperCalcemia)
who gets these/why is it special?
where is it located
-characterized by glands or mucin production
-most common cancer in Non-Smokers,
Large cell carcinoma
-no keratin pearls, no glands or mucin
central or periph
what kind of cells, whats growth look like
well differentiated, nest of nueroendocrine cells
polyp like growth
Lung cancer (general facts)
where does it metastisize?
Where does it get mets from?
what complications does it cause
mets to the adrenals
mets from the breast, colon, prostate
SPHERE of complications
-Superior Vena Cava syndrome, Pancoast tumor, Horner syndrome, Endocrine (paraneoplastic), Recurrent laryngeal nerve (hoarseness), Effusions (plueral)
What are the types and describe them
Accumulation of Air in the Pleural space
Spontaneous: Rupture of bleb or cysts. collapse of the lung w/ trachea shifting to collapse
Tension: caused by penetrating chest wall injury. trachea is pushed to opposite side of injury. (this is the one with the flap. air gets in but cant get out. pushes the trachea away)
how does it present?
what occupational hazard can cause this
Malignancy of the Mesothelial cells
Presents with recurrent pleural effusions
Whats up with DiGeorge Syndrome?
whats the deletion
how does it present?
Developmental failure of 3rd/4th pharyngeal pouch
-T-cell deficiency (Lack of Thymus)
-Hypocalcemia (Lack of parathyroid)
Whats up with SCID?
what are the deficiencies?
Defective cell mediated (T-cell) and Humoral mediated (B-cell) immunity
-Adenosine Deaminase Deficiency
MHC class II deficiency
-bubble boy/ bone marrow transplant
whats up with X-linked agammaglobulinemia
whats the defect?
when do you get it? why?
-fuck up of B-cell maturation
complete lack of immunoglobulins
-defect in BTK (Bruton Tyrosine Kinase)
-After 6 months of life which is when maternal IgG depletes
Common Variable Immunodeficiency
-increased risk of autoimmune dz and lymphoma
Selective IgA deficiency
What type of infections
-low serum IgA (duh)
Hyper IgM Syndrome
wheres the mutation
what type of infections?
increased levels of IgM
mutation at CD40L (cant class switch)
-decreased IgA, IgE, IgG
Pyogenic infections, mucosal infections
-Mutation in WAS gene
-Wiskott Aldrich Thrombocytopenia Eczema Recurrent infections
Systemic Lupus erythematosus
-Malar "butterfly" Rash. Chronic inflam, Arthritis, CNS psychosis
Renal Damage (Cause of death)/ Heart problems
Libman-Sacks-Endocarditis (SLE-->LSE) Vegetations on both sides of a valve
-Antinuclear antibody (ANA) + Anti-dsDNA
What are the Lupus causing drugs?
what antibodies do they produce?
Hydralazine, procainamide, Isoniazid
what are the two antibodies?
what can they lead to?
Associated with Lupus
Autoantibody associated with proteins on phospholipid. Hypercoag state
Anticardiolipin + lupus anticoagulant (falsely increases PTT)
false positive syphillis test
-life long anticoag tx
lab test? what other dz is SS associated with?
what could enlarged parotids lead too?
Autoimmune destruction of Lacrimal and Salivary glands.
-dry eyes, dry mouth, dental carries
-presence of ANA: Anti-SS-A/ Anti-SS-B (ribonucleoproteins)
-enlarged parotids=could mean B Cell Lymphoma
Diffuse vs Localized
Triad: Autoimmunity, noninflam vasculopathy, Collagen depositions w/ Fibrosis
Diffuse: widespread involvement of skin and viscera. Anti SCL-70 antibody (Anti-DNA Topoisomerase I antibody)
Localized: local skin involvment of fingers and face. CREST syndrome- Calcinosis/anti Centromere ab, Raynauds, Esophageal dysmotility, Sclerodactyly, Telangeictasia
Mixed Connective Tissue Dz
whats the antibody?
Grab bag of a lil bit of SLE, Scleroderma, polymyosistis
Anti-U1 RNP antibodies
What are the layers of the epidermis? from surface to deep. what are found in each
Stratum Corneum (keratin)
Basale (stem cells)
Whats atopic dermatitis?
where does it usually appear?
what type of hypersensitivity?
face and flexor surfaces
what type of hypersensitivity
Poison Ivy, Nickel, neomycine
Type IV (delayed)
-remove offending agent/topical steroids
whats it due to?
what type of infection
comedones (white heads and black heads), pustules (pimples)
Chronic inflammation of the hair follicles and sebacious glands
Proprionibacterium acnes (P. acnes)
-retinoids, benzoyl peroxide, antibiotics
whats it look like/ where is it found
whats another clinical sign it can be found with?
whats Auspitz sign?
excessive keratin proliferation: Parakeratosis (nuclei still in Stratum Corneum)
well-circumscribed "salmon colored" plaques with silvery scales
-extensor surfaces and scalp
Auspitz: pinpoint bleeding after removing a scale
how does histo look?
which other infection is it associated with?
Pruritic, purple, polygonal planar papules and plaques
-Sawtooth infiltrates of Lymphocytes at dermal-epidermal junciton
whats histo like? what layer is messed up
whats the clinical sign/finding?
what does immunoflourescence look like?
which type of skin does it involve?
Autoimmune destruction of Desmosomes via IgG antibodies
-tombstone appearance since basment cells are intact while the Stratum Spinosum is fucked up
-Separation of epidermis upon touching the skin (wet blisters)
-skin and oral mucosa
what will immunoflourescene look like?
how do the blisters look?
Autoimmune Destruction of Hemidesmosomes via IgG antibodies
oral mucosa isnt affected
-Tense Blisters that dont rupture easily
what do the lesions look like?
what dz is associated?
how do you treat it?
Depositions of IgA at tips of dermal papillae.
-herpes; so tiny vesicles that are grouped together
-dapsone/gluten free diet
what kind of skin lesions?
what are some associations?
Hypersensitivity reaction w/ Target Lesions
-HSV, M. pnuemo, sulfa drugs
Steven Johnson Syndrome
Erythema Multiforme w/ oral mucosa and Fever
-Toxic epidermal necrosis: Sloughing off of the skin
whats it called when you have a sudden appearance of these?
morgan freeman, looks stuck on
Leser-Trelat sign: sudden onset, usually a sign of malignancy (usually GI)
(thick epidermis) (dark)
what is it? where is it usually found?
what causes/associated with it?
Thickening of the skin
usually on the groin or axilla
-diabetes, obesity, cushings, malignancy
Basal cell carcinoma of the skin
what are the risk factors?
whats it look like?
whats a key finding on histo?
most common skin cancer
-exposure to UV sunlight
-raised lesion/central ulcer/dilated blood vessels (telangiectasias)
Squamous cell Carcinoma of the skin
what are some risk factors?
where is it usually found?
whats usually its precursos
malignant proliferation of squamous cells
-sunlight, immunosupression, arsenic
precursor to squamous cell
well differentiated SCC
volcanic lesion that forms quickly and resolves quickly as well
what level in the skin are mealoncytes found?
what embryo structure is it derived from?
where does it synthesize melain?
in the Basal cells
-synthesizes melanin in the melanosome
Autoimmune destruction of the melanocytes
- localized loss of skin pigmentation
whats the enzyme defect?
what are the 2 types?
what can it lead to?
Congenital lack of pigmentation
--defect in Tyrosine transport (impairs melanin production)
-eyes or eyes/skin
-increased risk of skin cancer
why are freckles present/darker than rest of skin?
they have increased number of melanosomes in their cells
hyperpigmentation of the cheeks associated with pregnancy or OCP use
whats a junctional nevus?
Junctional: increased melanocytes at dermal-epidermal junction. these guys are Flat
Malignant neoplasm of melanocytes
most common cause of Death in skin cancer
nodular: bad prognosis, creates huge bump
lentignious: good prognosis (radial prolif along the dermal epidermal junction)
acral: on the hands and feet of dark skinned ppl
skin infeciton caused by SA and Strep pyogenes
Honey colored crusting
deep skin infection (bacteria to the dermis
red, tender swollen rash
-trauma, bug bite, surgery
Necrosis of Subcutaneous tissue below the dermis
caused by anaerobic flesh eating bacteria
produciton of CO2 leads to crepitus
Staph scalded skin syndrome
difference between this and TEN (toxic epidermal necrosis)
Exotins A&B destroy keratinoctye attachments in stratum granulosom from rest of skin
-sloughing of skin with rash and fever
-TEN has separation at the dermal-epidermal junction where as SSS is stratum granulosom
which hormones do prolactin inhibit
what inhibits prolactin secretion
whats sheehan syndrome
what are some clinical signs
In pregnancy the pituitary gland doubles in size, however, the blood flow doesnt increase to match it so it doubles in size
-poor lactation and lossof pubic hair
what is it? whats main cause
Warty neoplasm of genital area
-HPV 6 and 11.
Thinning of the epdiermis/fibrosis of the dermis of the vag
-cigarrete "parchment" paper skin
lichen simplex chronicus
what causes it
hyperplasia of vulvar epithelium
-thickening of the skin
-chronic itching and scratching
Pagets dz of the vulva
malignant epithelial cells of the epdiermis
-erythematous, pruritc, ulcerated skin
Clear Cell Adenocarcinoma
whats an old drug that causes this?
Malignant proliferation of glands with clear cytoplasm
malignant mesenychmal cells of immature skelatal muscle
Lymph node spread of upper and lower vag carcinomas
upper 2/3 -- inguinal
lower 1/3 - illiac nodes
What causes acute endometriitis
left over products of conceptions
painless uterine bleeding
endometrial glands and stoma outside the uterine lining
whats a chocolate cyst?
its when the ovary is filled by endometriosis
Extension of the endometrial tissue (endometriosis) into the myometrium
what causes it?
how does it present
most important predictor for progression to carcinoma?
abnormal endometrial GLAND proliferation (relative to stroma)
-excess estrogen stimulation
-post menopausal vaginal bleeding
how does it present
Malignant prolif of endometrial glands
post menopause bleeding
how dangerous are they?
Benign proliferation of smooth muscle from myometrium
multiple, well-circumscribed tumors that increase during pregnancy
-asymptomatic, but sometimes can cause bleeding
whats the functional unit of the ovary?
Polycystic Ovariand Dz (PCOD)
what causes it?
what can it usually lead to?
hormone imbalnce -> incr. LH/ low FSH
-too much LH leads to incr. androgen production. that androgen goes to the periphery and gets converted to estrogen which then goes to pituitary and shuts down FSH (neg. feedback)
w/o FSH the ovary atrophies and creates a cyst
-obese woman, hirsutism, infertiliity,
when would you use the serum marker CA 125
to monitor for treatment and Recurrance
Mature cystic teratoma of the ovaries
what type of tumor (Surface epithelia, Germ cell, Sex cord stroma)
what do the cysts contain
Immature cystic teratome
Contains fetal tissue from all 3 germ layers
Immature contains immature tissue (ie neuroectoderm)
cystic teratoma composed of thyroid tissue
malignant ovarian tumor
Sheets of uniform "fried egg" cells (large cells with central nuclei and clear cytoplasm)
Yolk sack tumor (whats another name for it)
most common germ cell in ____
whatst the major tumor marker
what cells do you see on histo
Endodermal sinus tumor
most common germ cell in kids
Schiller-Duval bodies (central vessel looks like glomeruli) *glomeruloid like structures
whats it composed of?
how does it spread?
Malignant prolif of placenta tissue
-trophoblasts and Syncytiotrophoblasts
Villi are absent
Very high ß-hCG
Granulosa-Theca cell tumor
sex cord stromal tumor
neoplasm of granulosa/theca cells (duh)
production of estrogen/progestorone which will have differnt affects at different ages
Associated with _____ syndrome. which is
Benign tumor of Fibroblsts
Meigs Syndrome: Fibroma, Ascites, Hydrothorax
what does it secrete?
Gi malignancy that mets to ovaries
mucin secreting signet cell adenocarcinoma
where does it usually come from
intraperitoneal accumulation of mucin material
usually arises from Appendix tumor
whats the most common site?
big risk factor?
fertilization and implantation of ovary at site other than uterine wall.
-ampulla of Fallopian tubes
-scarring (from PID-salpingitis, endometriosis)
-lower abdominal pain after missed period (ALWAYS DO PREGNANCY TEST)
loss of fetus before 20 wks
passage of fetal tissues
Accreta: placenta attaches to myometrium w/o penetration. difficulty delivering placenta
Preeclampsia w/ thrombotic microangiopathy of the liver
Hemolysis, Elevated Liver enzymes, Low Platelet
Sudden infant Death Syndrome (SIDS)
Death of infant 1mo. - 1 yr. without cause
-sleeping on stomach, smoking in house,
how do you diagnos
instead of growing a baby you grow abnormal placental tissue
swollen and edematous villi, proliferation of trophoblasts
-passage of "grape-like" masses / snowstorm on US
-dilation and curettage of mole, monitor b-hcg
Complete Hydatidiform Mole
whose fault? fetal parts? villi? b-hcg
All dads fault (only sperm and enucleated egg)
46,XX; 46, XY
-no fetal parts
-All villi are edematous/fucked up
-b-hcg much higher than partial mole
Partial Hydatiform mole
fetal tissue? villi?
2 sperm + 1 egg
69 XXX; 69, XXY; 69, XYY
Yes fetal parts
some villie are fucked
What causes Hypospadias?
failure of the urethral folds to fuse
pee out the bottom of your weewee
what causes Epispadias?
what other abnormality is it associate with?
faulty positioning of the genital tubercle
bladder Extrophy (protrusion of the bladder)
Squamous cell carcinoma of the penis
major risk factors
malignant prolif of squamos cells of the penis
High risk HPV/lack of circumcision
-Bowens dz: shaft
Erythoplasia of Queyrat: glans
Bowenoid papulosis: reddish papules
-usually self resolving but after age 2 it can lead to testicular atrophy/increased risk of seminoma
which side is most common
"Bag of worms"
-usually left sided due to drainage into left renal vein
what causes testicular hydrocele?
incomplete obliteration of processus vaginalis (infants)
or blockage of lymph drainage (adults)
buzzwords for clinical presentaiton?
-Tender and Boggy
Lower back/pelvic pain
Benign prostatic hyperplasia
what causes it
what it can lead to
hyperplasia of the prostate around the lateral/middle lobes. increased PSA
-increase of DHT
-tx: a-blocker (terazosin), 5a-reductase inhibitor
how is it diagnosed
where does it met to?
Malignant prolif of prostatic glands
Most common cancer in men
arises in peripheral zone
-diagnosed by Incr. PSA / decr. fraction of free PSA
-mets to the bone (lower back pain)
What are the lobules and ducts lined by in the breast?
luminal cell layer
myoepithelial cell layer (contractile function)
which organism causes this
infection of the duct, purulent discharge
what does the biopsy show?
benign lump due to injury to breast tissue
necrotic fat with calcifications and giant cells
most common in premenopausal women
lumpy breasts, Blue dome cysts
whats Sclerosing adenosis
fibrosis of the acini and stroma of the breast
associated with calcifications
most common cause of _________
papillary= long like finger pertrusion in the lactiferous duct
most common cause of BLOODY NIPPLE
Most common tumor in premenopausal females
tumor of fibrous tissue and glands
well circumscribed, mobile, marble like
benign breast tumor with Leaf like lobulations
Ductal carcinoma in Situ (breast)
how is it detected on mammography
whats the comedo subtype
Malignant proliferation of cells in ducts
No invasion into the basement membrane
-Comedo:high grade cells w/ necrosis and dystrophic calcification in center
Paget's dz of the breast/nipple
how does it present?
DCIS that extends to the nipple
Invasive ductal Carcinoma (breast)'
advanced tumors can cause ____
forms rock-hard "duct like" structures
-dimpling of skin / retraction of nipple
Inflammatory breast cancer
what does the breast look like?
Cancer of the Dermal lymphatics
Peau d'orange (breast dimples like orange skin)
pretty bad prognosis
Invasive lobular carcinoma
how does it look?
Orderly row (Indian file) of cells due to decr. E-cadherin
Whats a pleomorphic adenoma
whats it composed of?
where does it usually arise?
whats the tumor look like? special about it?
A bening mixed tumor of the salivary glands
-most common salivary gland tumor
-composed of stromal and epithelial cells
-mobile, painless, and circumscribed
-high rate of recurrance
benign cystic tumor with germinal centers
-contains lymphnode tissue
most common malignant tumor of the salivary glands
-mucinous and squamous components