Idiopathic thrombocytopenic purpura (ITP)

o IgG against platelets

o Hyperplasia of megakaryocytes in bone marrow
o Spleen is making the antibodies then destroys platelets
Microangiopathic hemolytic anemia
o Platelet microthrombi in small blood vessels
o RBC sheared and become schistocytes
Thrombotic Thrombocytic purpura (TTP)
o Deficiency ADAMSTS13 which normally cleaves vWf multimers
o Can form a platelet microthrombi
o Often due to autoantibody presents in older women
Hemolytic uremic syndrome
o Ecoli01587 damages endothelial cells form platelet microthrombi
Bernard-Soulier syndrome
o GP1b deficiency so less platelet adhesion
o Platelets thus are bigger and less in number
Glanzmann thrombasthenia
o GP2b/3a deficiency so less platelet aggregation
Aspirin induced platelet change
o Blocks cyclooxygenase, thus less less TXA2 so calls less platelets
Uremia
o Nitrogenous buildup from renal problem causes platelet adhesion and
aggregation problem
Hemophilia A
o Factor 8 deficiency XLR
Hemophilia B
o Factor 9 deficiency
Anti-factor 8
o Antibody against coagulation factor
o Differentiate from Hemophilia by mixing with normal serum
Von Willebrant Disease
o Problem with platelet adhesion, so increased bleeding time
o Increased PTT because vWF stabilizes factor 8
o Abnormal ristocetin test, treat with desmopressin to release vWF
Vitamin K deficiency
o 2,7,9,10, C, S all need gamma-carboxylation
o Epoxide reductase activates vitamin K (Coumadin blocks epoxide red)
Liver failure hemostatic factor
o Decreased coagulation factor prod., less epoxide reductase (vit K)
Heparin-induced Thrombocytopenia (HIT)
o Heparin binds platelet factor 4 and thus IgG binds and causes platelet
destruction which can then activate other platelets causing
thrombosis
o Would want to give an anti-coagulant
Disseminated Intravascular coagulation (DIC)

o Pathologic activation of coagulation cascade causing microthrombi

o Consumes platelets and factors so have bleeding (fibrin breaks to Ddimer)
o Almost always secondary to another disease
Fibrinolysis problem
o Excess plasmin causes breakdown of coagulation factors but normal
platelets
o Fibrinogen breaks, no clot so no fibrin so no D-dimer from fibrin split
Cystathione beta synthase deficiency (CBS)
o Cant convert homocystein to homocystothionine
o Excess homocysteine in blood promotes thrombosis
Protein C/S deficiency
o Normally Protein C/S inactivate Factors 5/8
o Increased risk of Coumadin (warfarin) necrosis
Factor 5 Leiden
o Mutated factor 5 that cannot be shut down by protein C/S
Prothrobin 20210A
o Overexpression of prothrombin, thus promotes thrombus formation
Anti-Thrombin III deficiency
o Endothelial cells normally produce Heparin like Molecules (HTM)
which normally bind and promote ATIII which prevents thrombus
Oral contraceptive thrombosis
o Estrogen induces coagulation factors
o Thus important to check if someone smoking
Atheroscelrotic embolus
o Plaque that dislodges
o Will notice cholesterol clefts in the embolus
Fat embolus
o Usually associated with bone fractures
Gas embolus (decompression sickness)
o Caisson disease when chronic nitrogen embolus
o Can happen during laproscopic surgery
Amniotic fluid embolus
o Amniotic fluid lodges in womens lungs
o Amniotic fluid has tissue-thromboplastin which can cause DIC
Pulmonary embolus
o Often DCT can cause thromboembolus which goes to lungs
o Lung has dual blood supply so can be silent and resolve
Iron deficiency anemia
o Lack of iron in nutrition (1/3 of world is deficient)
o Causes microcytic hypochromic anemia because less hemoglobin
(early stage is normocytic, however)
Plummer-Vinson syndrome
o Mucosal protrusion in esophagus which presents with iron deficiency
anemia

Anemia of chronic disease (ACD)

o Chronic disease results in Hepcidin release which sequesters iron into
storage sites
o Bacteria need iron for survival, so body tries to hide away the iron
(dont take iron supplements if chronic infection)
Sideroblastic anemia
o Due to defect in protoporphyrin synthesis which forms ringed
sideroblast consisting of iron in mitochondria (and iron overload)
o Rate limiting step of heme synthesis enzyme is ALAS (needs B6)
Thalassemia
o Decreased globin chains and thus less Hb
o Alpha thalassemia from deletions, beta thalasemmia from mutations
Folate/B12 deficiency
o Megaloblastic anemia because not enough DNA precursors
o Hypersegmented neutrophils, rapid growth in other epithelial cells
B12 deficiency
o Takes years to develop because of large liver stores of B12
o Pernicious anemia can destroy parietal cells (less IF so less B12
uptake in ileum)
o Methylmalonic acid does not become succinyl coA so MMA buildup
can result in subacture combined degeneration of spinal cord
Extravascular hemolysis
o Reticuloendothelial system eats red blood cells and dumps the
byproducts resulting in jaundice and bile stones
Intravascular hemolysis
o RBC broken in blood but hemoglobin here just goes into blood and
binds haptoglobin
o Late presentation of hemosiderinuria
Hereditary spherocytosis
o Defect of RBC cytoskeleton tethering proteins making RBC round and
less able to maneuver through spleen (thus eaten)
o Can treat with splenectomy, but can result in Howell-Jolly body
o Breaks during osmotic fragility test
Sickle cell anemia
o AR mutation of B chain, glutamic acid replaced with valine
(hydrophobic)
o HbS polymerizes when deoxygenated which causes shape change
which can result in vaso-occusive crisis
Hemoglobin C
o Glutamic acid is replaced by lyCine
Paroxysmal nocturnal hematuria
o Acquired defect myeloid such that there is no GPI so no DAF or MIRL
so cells are susceptible to complement destruction which happens a
lot at night because of more CO2
o destroyed platelets promotes thrombosis which results in death

G6PD deficiency
o NADPH needed to regenerate reduced glutathione which is important
for breaking down oxygen radicals
o Results in Heinz bodies which are bitten off as bite cells and results in
intravascular hemolysis
Immune hemolytic anemia
o IgG or IgM binds to RBC which breaks it down
o IgG broken in splenic macrophage thus spherocytosis results
o IgM fixes complement and occurs in cold temp of extremities
Microangiopathic hemolytic anemia
o Schistocytes from microthrombi, prosthetic valves, or aortic stenosis
Malaria anemia
o Plasmodium lives within the RBC and breaks the cell
Parvovirus B19 infection
o Infects progenitor cells and halts erythropoiesis
Aplastic anemia
o Damage to hematopoietic stem cells so pancytopenia
o Can be caused by some drugs and treated with marrow stimulation
Myelophthisic process
o Process that replaces bone marrow resulting in pancytopenia
Neutropenia
o Low number of neutrophil during chemotherapy because they dont
divide or severe infection because neutrophils have gone into tissue
Lymphopenia
o Immunodeficiency, high cortisol state, whole body radiation can
decrease lymphocyte cells
Neutrophilic leukocytosis
o Due to bacterial infection or tissue necrosis that causes immature
neutrophils to be increasingly released into circulation
Monocytosis
o Increase in number of monocytes due to chronic inflammation and
malignancy
Eosinophilia
o Allergic reactions, parasitic infection, and Hodkin lymphoma due to
increased Il-5 production
Basophilia
o Classically associated with CML
Lymphocytic leukocytosis
o Viral infections because CD8+ cells needed
Infectious mononucleosis
o Commonly EBV infection (also CMV) promotes CD8+ cell proliferation
and lymphocytic leukocytosis
ALL
o B-ALL and T-ALL increase in blasts
AML

o MPO seen as Auer rods indicates myeloblast accumulation

Myelodysplastic syndrome
o Ineffective production of myeloid class of blood cells and results in
cytopenia
Chronic lymphoid leukemia
o Neoplastic proliferation of nave B-Cells
o B cells end up producing fewer immunoglobulins
Hairy cell leukemia
o Proliferation of B cells and cytoplasm has hairy outgrowths
o TRAP can test for this, and B cells trapped in red pulp and bone
marrow
Adult T Cell Leukemia Lymphoma (ATLL)
o Helper T cell proliferation associated with HTLV-1 virus
o Lytic bone lesions/ hypercalcemia (Multiple myeloma) + rash
Mycosis fungoides
o Neoplastic proliferation of CD4+ T cells, and creates skin rashes
(Pautrier microabscesses)
o When it spreads to blood becomes Sezary Syndrome
Chronic Myeloid Leukemia
o Proliferation of mature myeloid, especially granulocytes (Basophils)
o T(9;22) which causes BCR-Abl fusion and increased Tyrosine Kinase
activity
o Similar presentation but different than leukemoid reaction (infection)
Polycythemia Vera
o JAK2 kinaste mutation results in increased mature myeloid especially
RBC
o Different than reactive polycythemia because here less EPO produced
Essential Thrombocythemia
o JAK2 kinaste mutation results in increased mature myeloid especially
platelets
o Unlike other myelodysplastic, there is no hyperuricemia/gout
Myelofibrosis
o Neoplastic mature myeloid especially megakaryocytes which
produces excess platelet derived growth factor leading to bone
marrow fibrosis (thus spleen takes over Hematopoiesis)
Follicular lymphoma
o Neoplastic small B cells that make follicle-like nodules
o BCl2 (18)-IgH(14) translocation thus there is inhibition of apoptosis
in follicle region (where somatic hypermutation occurs)
Mantle cell lymphoma
o Neoplastic small B cells that expands to mantle region
o Cyclin D1 (chr. 11) to IgH (14) translocation
Marginal cell lymphoma
o Neoplastic small B cells that expands to marginal zone

o Associated with chronic inflammatory states because marginal zone

normally exists when there is activation in germinal center
MALToma
o Marginal cell lymphoma in mucosal areas such as stomach
Burkitt Lymphoma
o Neoplastic intermediate sized B cell when c-myc (chromosome 18)
onto chromosome 14 IgH
Diffuse large B-Cell lymphoma (DLBCL)
o Most common NHL that grows clinically aggressive
Hodkins lymphoma
o Reed-Sternberg neoplasm which secretes cytokines which pull in
other cells
o Various subtypes of HL
Multiple myeloma
o Malignant proliferation of plasma cells in bone marrow which result
in osteoclast activation
o M spike of gamma globulin, and free light chains can deposit places
Monoclonal Gammopathy of Undetermined Significance
o Multiple myeloma M spike without other symptoms
Waldenstrom Macroglobulinemia
o B-cell lymphoma with monoclonal IgM (which is big pentamer)
o M spike with increased IgM
Langerhans cell histiocytosis
o Neoplastic Langerhans cell growth (dendritic cells present antigen on
skin)
o Various subtypes (Letterer-Siwe disease, Eosinophilic granuloma,
Hand-Schuller-Christian)
Temporal (giant cell) arteritis
o Older adults with granulomatous vasculitis and often carotid arteries
Takayasu Arteritis
o Less than 50 with granulomatous vasculitis
o From aortic arch branch points instead of distal like giant cell arteritis
Polyarteritis nodosa
o Necrotizing muscle artery vasculitis that spares lungs
o Looks like beads on a string
Kawasaki disease
o Classically young Asian children and nonspecific symptoms commonly
involving coronary artery
o Give aspirin which is interesting because dont give aspirin for viral
infection
Buerger Disease
o Often from smoking results in necrotizing vasculitis in digits
Wegener Granulomatosis
o Necrotizing granulomatous vasculitis affects nasopharynx, lungs, and
kidneys

Microscopic Polyangiitis
o Like Wegeners except here no nasopharygeal onvolvement and PANCA instead of c-ANCA
Churg-Strauss Syndrome
o Necrtotizing granulomatous vasculitis with eosinophils with asthma
and p-ANCA
Henoch-Shonlein Purpura
o IgA immune complex deposition with palpable purpura because there
is inflammation along with vasculitis
Atherosclerosis
o Intimal plaque that obstructs blood flow often in medium and large
sized arteries
o Lipid deposits within intima and then gets oxidized and inside
macrophage
Arteriolosclerosis
o Narrowing of small arterioles, two types hyaline (BHT and diabetic
glycosylation which lets proteins in) and hyperplastic (due to
hyperplasia of the smooth muscle from malignant HT)
Monckeberg Medial Calcific Sclerosis
o Non-obstructive calcification of the Medial region but not clinically
significant
Aortic dissection
o Blood rips through media of Aorta near the heart because of
preexisting weakness of the media
Abdominal aortic aneurysm
o After aorta but before the bifurcation of descending aorta
Stable angina
o Reversible injury of myocytes caused by atherosclerosis
Unstable angina
o Rupture of a plaque results in thrombosis which partially occludes the
myocardial vessel
Prinzmantel angina
o Coronary artery vasospasm that results in pain to myocytes but not
death
o Transmural ischemia so you get ST elevation
Myocardial infarction
o Death of myocytes due to atheroscleoris which results in complete
thrombus
Dressler syndrome
o Autoantibody against pericardium after infarction
Left heart failure
o Due to various causes importantly leads to blood buildup in lungs
o Decreased forward perfusion can lead to exasperation (treat with
ACEI)
Right heart failure

o Most common cause is left heart failure, Left-to-right shunt

o Cor pulmonade is when right heart fails due to lung problems
VSD
o Left to right shunt that results in lots of blood into lungs but later
leads to pulmonary HTN that results in Right-to-left shunt
o Large defects can lead to Eisenmenger syndrome
ASD
o Left-to-right shunt that results in delayed pulmonary valve closure
(S2 split)
o Can cause paradoxical embolus not in pulmonary
Patent Ductus arteriosus (PDA)
o Eisenmenger syndrome is when shunt reverses after pulmonary HT
which results in non-oxygenated blood to the system
Tetrology of Fallot
o Stenosis of pulmonary valve and VSD results in right-to-left shunt
leading to cyanosis and boot shaped heart on X-ray
Transposition of great vessels
o Two independent circuits that do not mix due to Aorta and
Pulmonary artery switching positions
o Keep baby alive by giving PGE to keep PDA open temporarily
Truncus arteriosus
o Truncus fails to divide into pulmonary and aorta leading to early
cyanosis
Tricuspid atresia
o Tricuspid valve does not work, associated with ASD that lets blood
into systemic circulation
Coarctation of Aorta
o Associated with PDA and before PDA so right to left shunt resulting in
cyanosis
o Adult form is not associated with PDA, and results in hypertension in
upper extremities and hypotension in lower extremities which needs
collateral circulation which results in notching
Acute rheumatic fever
o M protein antibodies also resembles human tissues (molecular
mimicry) and diagnosed by JONES criteria
o Mitral valve stenosis occurs, and aschoff bodies in myocardium
Aortic stenosis
o Narrowing aortic valve usually from fibrosis from wear and tear
o Compensation results in ejection-click and LV hypertrophy
Aortic regurgitation
o Most often from aortic root dilation or syphilitic aneurysm
o Hyperdynamic circulation
Mitral valve prolapse
o mid systolic click because mitral valve is ballooning back and can have
some regurgitation

Mitral regurgitation
o Mitral valve is letting some blood go back into atrium during systole
o Holosytolic murmur that gets louder with squatting and exhale
Mitral stenosis
o Chronic rheumatic would create stenosis while acute is regurgitation
o Opening snap followed by a diastolic rumble, volume overload can
lead to LA dilatation
Bacterial endocarditis
o S. viridans = Low virulence so affects previously affected endocardium
o S. aureus = High virulence so acute endocarditis
o S. epidermis = prosthetic valves
o S. bovis = endocarditis in patients with colorectal cancer
o HACEK = endocarditis with negative blood cultures
Nonbacterial thrombotic endocardititis
o Sterile Vegetation in valves often leading to mitral regurgitation
Libman-Sacks Endocarditis
o Sterile vegetations associated with SLE leading to mitral regurgitation
Dilated cardiomyopathy
o Dilation of all chambers resulting in valve regurgitation and arryhtmia
and CHF
Hypertrophic cardiomyopathy
o Massive hypertrophy in LV often due to genetic change in sarcomere
o Decreased CO (muscles so big) and can have random arryhtmia in
young children during exercise
Restrictive cardiomyopathy
o Various causes prevent heart from properly stretching
Myxoma
o Mesenchymal proliferation since since heart cells cant become
cancerous
Rhabdomyoma
o Benign hemartoma of cardiac muscle most common in children
o High association with tuberous sclerosis and usually in
ventriclepMain