DISORDERS OF PRIMARY HEMOSTASIS
Quantitative
 Immune thrombocytopenic purpura (ITP)
o MCC of thrombocytopenia
o IgG antibodies against platlet antigens
o Acute  children  after viral
infection  self-limited
o Chronic  women of childbearing age
 anti-platelet IgG can cross placenta
 a/w SLE
o Labs
 Low platelets, ↑megakaryocytes
in BM
 Normal PT/PTT
 Microangiopathic hemolytic anemia
o Thrombotic thrombocytopenic purpura
(TTP)
 ↓ADAMTS13  large multimers
of vWF
 CNS abnormalities
o Hemolytic uremic syndrome (HUS)
 E. coli O157:H7 dysentery in
children
 Kidney insufficiency
o Clinical manifestations:
 Skin and mucosal bleeding
 Fever
o Labs
 Low platelet count,
↑megakaryocytes
 ↑bleeding time
 Normal PT/PTT
 Anemia + schistocytes
Qualitative
 Bernard-Soulier syndrome
o Genetic GPIb deficiency  impaired
adhesion
o Enlarged platelets “Big Suckers”
 Glanzmann thrombasthenia
o Genetic GPIIb/IIIa deficiency 
impaired aggregation
 Aspirin  ↓TXA2 for aggregation
 Uremia disrupts both adhesion and agg
DISORDERS OF SECONDARY HEMOSTASIS
 Hemophilia A
o Factor 8 deficiency, X-linked
o Deep tissue, joint, post-sx bleeding
o Labs
 ↑PTT; normal PT
 Platelet count and bleeding time
normal
 Hemophilia B
o Factor 9 deficiency
o Like hemophilia 8
 Coagulation factor inhibitor
o Antibody against coag factor (MC
factor 8)
o Mixing study  PTT does NOT correct
(unlike in hemophilia 8)
 Von Williebrand Disease
o MCC of inherited coagulation d/o
o ↓vWF, AD inheritance
o Platelet adhesion problem  skin and
mucosal bleeding***
o Labs
 ↑bleeding time
 ↑PTT; normal PT (cannot
stabilize factor 8)
 Ristocetin  lack RBC
aggregation
o Desmopressin  vWF release from W-
P bodies
 Vitamin K deficiency
o Defective gamma-carboxylation of 2, 7,
9, 10, protein C and S
o Newborns lack vitK  give IV vitK
o Long-term abx (vitK production by bac)
o Malabsorption
 Liver failure
o ↓production of coagulation factors
o ↓epoxide reductase to activate vitK
o Follow PT
 Large-volume transfusion
o Dilutes coagulation factors
OTHER DISORDERS OF HEMOSTASIS
 Heparin-induced thrombocytopenia
o Heparin-PF4 complex  IgG antibodies
 complex ingested by spleen
o Fragments of platelets  thrombosis
 Disseminated intravascular coagulation
o Pathologic activation of coag cascade
o Widespread microthrombi  ischemia
and infarction
o Consumption of platelets and factors
 bleeding from IV sites and mucosal
surface
o Secondary to another dz:
 Obstetric complications, sepsis,
mucin from adenocarcinoma,
PML, rattlesnake bite
o Labs
 ↓platelet count, fibrinogen
 ↑PT and PTT
 Microangiopathic hemolytic
anemia
 ↑fibrin split products (D-dimer)
DISORDERS OF FIBRINOLYSIS
 Radical prostatectomy – release urokinase
 activates plasmin
 Cirrhosis of liver – reduce production of α2-
antiplasmin
 Increased bleeding (looks like DIC)
 Labs
o ↑PT and PTT
o ↑bleeding time with NORMAL platelet
count***
o ↑fibrin split products (NOT D-dimers*)
 Aminocaproic acid  blocks activation of
plasminogen
THROMBOSIS (Virchow’s triad)
Disruption in normal BF
o Stasis or turbulence
 Immobilization, cardiac wall dysfunc,
aneurysm
 Endothelial cell damage
o Atherosclerosis, vasculitis
o ↑homocysteine levels
 Vitamin B12 and folate deficiency
 Cystathionine beta synthase deficiency
 Thrombosis, MR, lens dislocation,
long slender fingers
 Hypercoagulable state
o Procoagulants > anticoagulants
o Protein C and S deficiency (AD)
 ↑risk for warfarin skin necrosis –
protein C and S have shorter T½***
o Factor V Leiden
 MCC of inherited hypercoag state
 Mutated factor V that is resistant to
cleavage by protein C or S
 Prothrombin 20210A
o ↑prothrombin gene expression
 Antithrombin III deficiency
o ↓heparin-like molecules
o PTT does NOT rise w/ heparin
 OCPs – Es increase production of
coagulation factors
EMBOLISM
 Thromboembolism – most common
 Atherosclerotic embolism – contains
cholesterol clefts
 Fat embolus – long bone fractures
o Dyspnea & petechiae on chest
 Gas embolus –
o Decompression sickness
o Caisson dz – multifocal ischemic
necrosis of bone
o Laparoscopic surgery
 Amniotic fluid embolus – keratin debris
o During labor/delivery
o SOB, neurologic symptoms, DIC
 Pulmonary embolism
o MCC from DVT
o Most often clinically silent
o SOB, hemoptysis, pleuritic chest pain,
pleural effusion
o V/Q mismatch
o ↑D-dimer
o Hemorrhagic wedge-shaped infarct
o Saddle embolus  sudden death
o Chronic PE  pulm HTN
 Systemic embolism
o MCC from L heart
o Mostly affects lower extremities
MICROCYTIC ANEMIA (<80 μm3)
 Iron deficiency anemia
o MCC of anemia, initially normocytic
o Newborns  breast milk
o Children  poor diet
o Adult males  PUD
o Adult females  menorrhagia
o Elderly  colon polys/CA or
hookworm
o Anemia, koilonychias (spoon), pica
o ↓ferritin, ↑TIBC***
o ↓serum iron, ↓%sat
o ↑RDW, FEP
o a/w Plummer-Vinson syndrome –
anemia + dysphagia (esophageal web)
+ beefy-red tongue
 Anemia of chronic disease
o ↑production of hepcidin (acute phase
protein)
 Limits iron transfer from
macrophages to erythroid
precurosis
 Also ↓EPO production
o ↑ferritin, ↓TIBC***
o ↓serum iron, ↓%sat
o ↑RDW, FEP
 Sideroblastic anemia
o ↓protoporphyrin (component of
heme)
o Fe + protoporphyrin in mitochondria
 Fe trapped in mitochondria 
ring around nucleus
o ALAS congenital deficiency
o Alcoholism – mito poisoning
o Lead poisoning – ALAD and
ferrochelatase
o Vit B6 deficiency a/w isoniazid
o ↑ferritin, ↓TIBC***
o ↑serum iron, ↑%sat*** (overload)
 Thalassemia
o ↓synthesis of globin
o Protective against P. falciparum
 α-thalassemia
o 1 gene deletion – asymp
o 2 gene deletion
 Cis (Asians) – a/w with Sabs
 Trans (Africans)
o 3 gene deletion – severe anemia
 HbH = β-chain tetramers
o 4 gene deletion – hydrops fetalis
 Hb Barts = γ-chain tetramers
 β-thalassemia – due to gene mutations
o Minor (β/β+) – asymp
 Microcytic, hypochromic RBCs
and TARGET CELLS
 slightly ↓HbA, ↑HbA2 and HbF
o Major (β⁰/ β⁰) – most severe
 α tetramers  damage RBC 
ineffective erythropoiesis
 massive erythroid hyperplasia 
“crew cut”, chipmunk facies,
hepatosplenomegaly
 hepatic aplastic crisis w/
parovirus B19
 Microcytic, hypochromic RBCs
and TARGET CELLS
 Also have nucleated RBCs
 NO HbA, ↑HbA2 and HbF
MACROCYTIC ANEMIA (>100 μm3)
 Folate deficiency
o Absorbed in jejunum (stores last
months)
o Causes: poor diet, ↑demand, folate
antagonists (MTX)
o Macrocytic RBCs + hypersegmented
PMNs
o Glossitis
o ↓folate, ↑homocysteine
o Normal methylmalonic acid*** 
shows vit B12 is normal
 Vitamin B12 deficiency
o Absorbed in ileum, requires intrinsic
factor (stores last years)
o Causes: pernicious anemia, pancreatic
insufficiency, dmg to terminal ileum,
dietary deficiency rare unless vegan
o Macrocytic RBCs + hypersegmented
PMNs
o Acute combined degen of spinal cord*
o ↓vit B12, ↑homocysteine
o ↑methylmalonic acid*** inhibits
myelination
[homocysteine  ↑risk of thrombosis]
NORMOCYTIC ANEMIA
Predominant extravascular hemolysis
-UNCONJUCATED BILIRUBIN
-splenomegaly, jaundice, bilirubin gallstones
 Hereditary spherocytosis
o Defect of spectrin, ankyrin, band 3.1
o Spherocytes w/ loss of central pallor
o ↑RDW, ↑MCHC***
o Splenomegaly, jaundice, bilirubin
gallstones
o ↑risk of aplastic crisis w/ parovirus
B19
o Osmotic fragility test - ↑fragility
o Tx: splenectomy  Howell-Jolly bodies
 Sickle cell anemia
o β-chain mutation: glutamic acid 
VALINE
o Homozygous  >90% HbS
o Hypoxemia, dehydration, acidosis 
deoxygenation  HbS polymerization
o HbF at birth is protective (presents
around 6 mos of age)  tx with
hydroxyurea to increase HbF
o Extravascular, intravascular hemolysis
 TARGET CELLS
o Massive erythyroid hyperplasia
o Irreversible sickling  dactylitis,
autosplenectomy (vaccinate kids
against encapsulated organisms, H-J
bodies), acute chest syndrome, pain
crisis, renal papillary necrosis
o Metabisulfite screen  causes cells to
sickle
o 90% HbS, 8% HbF, 2% HbA2, no HbA
 Sickle cell trait
o Heterozygous  <50% HbS
o Asymptomatic (no sickling)
o Extreme hypoxia and hypertonicity of
renal medulla  causes sickling 
microinfarctions, hematuria, ↓ability
to conc. urine
o 55% HbA, 43% HbS, 2% HbA2
 Hemoglobin C
o β-chain mutation: glutamic acid 
LYSINE
o Extravascular hemolysis  mild
anemia
o HbC crystals***
Predominant intravascular hemolysis
-hemoglobinemia, hemoglobinuria
-hemosiderinuria (HEMOSIDERIN)
-↓free serum haptoglobin
 Paroxysmal nocturnal hemoglobinuria (PNH)
o Acquired absence of GPI
(glycosylphosphatidylinositol) in stem
cells  cannot attach DAF (CD55) 
lose protection from complement
o At night we are more acidotic 
activates complement  intravascular
lyses RBCs at night  dark urine in
morning
o Destroyed platelets  thrombosis
o Complications: iron deficiency anemia,
AML (10%)
 G6PD deficiency
o ↓G6PD, ↓NADPH, ↓reduced
glutathione
o African variant – mildly reduced T½ of
G6PD
o Mediterranean variant – markedly
reduced T½ of G6PD
o Oxidative stress (infection, drugs, fava
beans)  intravascular hemolysis
o Heinz bodies = Hb precipitates
 Removed by spleen  bite cells
o Hemoglobinuria + back pain
 Immune hemolytic anemia (IHA)
o IgG (warm)  extravascular hemolysis
 Spherocytes
 a/w SLE, CLL, drugs (PCN,
cephalosporins)
o IgM (cold)  intravascular hemolysis
 a/w mycoplasma pneumoniae
and infectious mononucleosis
o DIRECT Coombs – tests Abs that are
already bound to RBC
o INDIRECT Coombs – tests if pts serum
contains Abs
 Microangiopatheic hemolytic anemia
o Microthrombi, prosthetic heart valves,
aortic stenosis (schistocytes)
 Malaria
 o RBCs rupture due to plasmodium
 P falciparum  daily fever
 P vivax and ovale  fever every
other day
ANEMIA DUE TO UNDERPRODUCTION
 Parovirus B19
o Infects progenitor cells  temporarily
halts erythropoiesis  significant
anemia in setting of pre-existing
marrow stress
 Aplastic anemia
o Damages hSCs  pancytopenia w/ low
reticulocyte count
o Causes: drugs, chemicals, viral
infections, autoimmune damage
o Fatty, empty marrow
o Tx: stop cause, transfusion, marrow-
stimulating factors (EPO, GM-CSF, G-
CSF), last resort is BM transplant
 Myelophthisic process
o Pathologic process that replaces bone
marrow  pancytopenia
INFECTIOUS MONONUCLEOSIS
 Monospot test (detect IgM)
o EBV  (+) heterophile abs
o CMV  (-) heterophile abs
 Effects oropharynx, liver, B-cells
 CD8+ response
o Hyperplasia of lymph node
PARACORTEX
o Hyperplasia of spleen in PALS
 Atypical lymphocytes  large nucleus, lots
of cytoplasm, “kissing” surrounding cells
 Complications:
o Splenic rupture (avoid contact sports
for 1 year)
o Rash w/ ampicillin
o Dormancy in B-cells  recurrence and
B-cell lymphoma
ACUTE LEUKEMIA
 Acute lymphocytic leukemia (ALL)
o >20% lymphoblasts
o TdT+
o a/w children and Down syndrome
(arises AFTER age 5)
o B-ALL (most common)
 TdT+, CD10, CD19, CD20
 Response well to chemo
 Require direct injection for
prophylaxis into scrotum and CSF
 t(12;21) – children, good
prognosis
 t(9;22) – adults, poor prognosis
o T-ALL
 TdT+, CD2 through CD8
 Thymic mass in Teenager 
“lymphoma”
 Acute myelocytic leukemia (AML)
o Myeloperoxidase (MPO)  forms Auer
rods
 Activates complement  DIC
o MC in older adults
o Acute promyelocytic leukemia (APL)
 t(15;17)  translocation of
retinoic acid receptor (RAR) from
chromo 17  chromo 15
 RAR disruption  blocks
maturation of promyelocytes
 Tx: all-trans-retinoic acid
o Acute monocytic leukemia
 Monoblasts (lack MPO) 
accumulate in gums
o Acute megakaryoblastic leukemia
 Megakaryocytes (lack MPO)
 a/w Down syndrome (arises
BEFORE age 5)
o AML may arise from myelodysplastic
syndromes (after cancer treatment)
 Cytopenias, hypercellular BM,
increased blasts but <20%
 Most pts die from infection or
bleeding
CHRONIC LEUKEMIA
 Chronic lymphocytic leukemia (CLL)
o Naïve B-cells  CD5, CD20
o ↑lymphocytes and SMUDGE CELLS
o If cause generalize lymphadenopathy =
small lymphocytic lymphoma
o Complications:
 Hypogammaglobulinemia
 Autoimmune hemolytic anemia
 Richter transformation  into
diffuse large B-cell lymphoma 
enlarging lymph node or spleen
 Hairy cell leukemia
o Mature B-cells w/ hair cytoplasmic
processes
o TRAP+
o Splenomegaly (red pulp), BM fibrosis
o NO lymphadenopathy
o Good response to 2-CDA and
adenosine deaminase inhibitor
 Adult T-cell leukemia/lymphoma
o Mature CD4+ T-cells
o a/w HTLV-1 (Japan and Caribbean)
o rash, generalized lymphadenopathy,
hepatosplenomegaly, lytic (punched-
out) bone lesions w/ hyperCa2+
 Mycosis fungoides
o Mature CD4+ T-cells
 Skin rash, plaques, nodules
 Pautrier microabscesses
o Spread to involve blood  Sezary
syndrome  cerebriform nuclei
MYELOPROLIFERATIVE DISORDERS
-all myeloid cells increased
-↑risk of hyperuricemia/gout
-can progress into acute leukemia
 Chronic myeloid leukemia (CML)
o Predominant: granulocytes (esp
BASOPHILS)
o t(9;22)  fusion BCR-ABL  increased
tyrosine kinase activity
o enlarging spleen  accelerated phase
 transformationi into acute leukemia
 2/3 into AML, 1/3 into ALL
o LACK leukocyte alkaline phosphatase
(LAP)*** seen in leukemoid rxns
o tx: imatinib (Gleevac)
 Polycythemia vera
o Predominant: RBCs
o a/w JAK2 kinase mutation
o HYPERVISCOSITY of blood
 Blurry vision, headache
 ↑venous thrombosis (MCC of
Budd-Chiari syndrome***)
 Flushed face (plethora)
 Itching
o Tx: phlebotomy, hydoxyurea
Polycythemia vera Reactive polycythemia
↓EPO ↑EPO
Normal SaO2 Low SaO2
(a/w high altitude or
lung dz)
 Essential thrombocythemia
o Predominant: platelets
o a/w JAK2 kinase mutation
o platelets functioning  thrombosis
o platelets not functioning  bleeding
o rare progression to fibrosis and acute
leukemia
o no significant risk for hyperuricemia
 Myelofibrosis
o Predominant: megakaryocytes
o a/w JAK2 kinase mutation
o Produces PDGF  marrow fibrosis***
o Splenomegaly
o Leukoerythroblastic smear (tear-drop
RBC***s, nucleated RBCs, immature
granulocytes)
o ↑risk of infection, thrombosis,
bleeding
LYMPHADENOPATHY (LAD)
 Enlarged lymph nodes
o Painful  acute lymphadenitis
 o Painless  chronic lymphadenitis
o Cortex, follicles  B-cell region
 a/w HIV
o Paracortex  T-cell region
 a/w infectious mononucleosis
o Medulla  sinus histiocytes that are
draining a region of cancer
NON-HODKIN LYMPHOMA (60%)
-late adulthood, painless LAD
 Follicular lymphoma
o Small CD20 B-cells  form follicles
o t(14;18)  overexpression of Bcl2
o tx: rituximab
o enlarging lymph node may suggest
progression to large B-cell lymphoma
o destruction of normal lymph node
architecture
o monoclonal, lack tangible body
macrophages (white spots) in germinal
centers
 bitten” appearance
Mantle cell lymphoma
o Small CD20 B-cells  expands mantle
zone
o t(11;14)  overexpression of cyclin D1
 promotes G1/S transition
 OTHER VASCULAR LESIONS
Marginal zone lymphoma
o Small CD20 B-cells  expands
marginal zone
o a/w Hashimoto thyroiditis, Sjogren
syndrome, H. pylori gastritis (marginal
zone only present during chronic
inflamm)
o MALToma = marginal zone lymphoma
in mucosal sites
 
Burkitt lymphoma
o Intermediate-sized CD20 B-cells
o t(8;14)  overexpression of c-myc
onogene
o a/w EBV
o extranodal mass in child/young adult
 African  jaw
 Sporadic  abdomen
o starry sky appearance***
 Diffuse large B-cell lymphoma
o MOST COMMON form of NHL
 Sporadic or transformation of
low-grade lymphoma
o Large CD20 B-cells that grow in sheets
 HIGH grade (aggressive)
o Enlarging lymph node or extranodal
mass in adulthood
HODGKIN LYMPHOMA (40%)
 Neoplastic proliferation of Reed-Sternberg
(RS) cells = large B-cells w/ multilobed nuclei
+ prominent nucleoli  “owl-eyed nuclei”
 CD15, CD30***
 Nodular sclerosis
o MOST COMMON form of HL
o Cervical/mediastinal lymph node in
young adult (F>M)
o Divided by bands of sclerosis
 Lymphocyte rich  best prognosis
 Mixed cellularity  abundant eosinophils
 Lymphocyte depleted  most aggressive
o Seen in elderly and HIV-pts
PLASMA CELL DISORDERS (DYSCRASIAS)
 Multiple myeloma (MM)
o MC primary malignancy of bone
o High serum IL-6  plasma cell growth
o Bone pain + hyperCa2+ (RANK
activation  lytic lesions)
o M spike  monoclonal IgG or IgA 
infection = most common cause of
death
o Rouleaux formation of RBCs***
o Primary AL amyloidosis  Bence Jones
protein  deposition in kidney 
proteinuria
 Monoclonal gammopathy of undetermined
significance （MGUS）
o ↑serum protein with M spike
o Other features of MM missing
o Common in the elderly
 1%/yr
 Waldenstrom macroglobulinemia
o B-cell lymphoma w/ monoclonal IgM
o LAD
o ↑serum protein with M spike
o Hyperviscosity  visual and neurologic
deficits
o Bleeding
o Tx: plasmapheresis to remove IgM
LANGERHANS CELL HISTIOCYTOSIS
-Birbeck (tennis racket) granules
-CD1a, S100***
 Eosinophilic granuloma
o Benign
o Pathologic fracture in adolescent
o Langerhan cells mixed w/ eosinophils
 Letterer-siwe disease
o Malignant
o Skin rash, cystic skeletal defects in
infant <2 yrs
o Multiple organ involvement  rapidly
fatal
 Hand-Schuller-Christian disease
o Malignant
o Scalp rash, lytic skull defects, diabetes
insipidus, exophthalmos in child
SECONDARY HTN
 Renal artery stenosis
o Atherosclerosis  elderly male
o Fibromuscular dysplasia  young
female
o ↑RAAS
 ↑SVR, ↑plasma volume
o Unilateral atrophy of stenosed kidney
ATHEROSCLEROSIS
 Atherosclerosis
o INTIMAL thickening in medium/large
vessels
o Cholesterol w/ fibromuscular cap
o MC involve: abdominal aorta,
coronary, popliteal and internal
carotids
o Modifiable risk factors = HTN, DM,
hypercholesterolemia, smoking
o Complications:
 Only symptomatic with >70%
occlusion
 Stenosis of medium-sized vessels
 peripheral vascular dz, angina,
ischemic bowel disease
 Plaque rupture  thrombosis 
MI or stroke
 Emboli w/ cholesterol crystals
 Weakening of vessels 
aneurysm (abdominal)
 Arteriolosclerosis
o Hyaline – due to proteins leaking into
wall (PINK)
 a/w benign HTN and DM***
 classically produces glomerular
scarring
(arteriolonephrosclerosis)  CKD
o Hyperplastic – thickening via smooth
muscle hyperplasia  onion skinning
 a/w malignant HTN***
 classically produces AKI w/ “flea-
 Monckeberg medial calcific sclerosis
o MEDIAL thickening via calcification
o NOT clinically significant (non-
obstruction)
 Aortic dissection
o INTIMAL tear with dissection of blood
through media
o Proximal 10cm of aorta (highest stress)
w/ preexisting weakness of media
o Elderly  HTN  hyaline
arteriosclerosis of vasa vasorum 
atrophy of media
o Younger  inherited CT d/os
Marfan or Ehlers-Danlos  cystic
medial necrosis
o SHARP, tearing pain that radiates to
the back
o MCC of death = pericardial tamponade
 Thoracic aneurysm
o Classically seen in 3⁰ syphilis  “tree-
bark” appearance
 o Weakness in aortic wall (endarteritis of
vasa varsorum)
o Dilation of aortic root  aortic insuff
 Abdominal aortic aneurysm
o Usually below renal arteries but above
aortic bifurcation
o Male smokers >60 yrs old w/ HTN
o Atherosclerosis  reduces diffusion to
media  atrophy and weakness
o If >5cm  ↑risk of RUPTURE 
hypotension, pulsatile abd mass, flank
pain
VASCULAR TUMORS
 Hemangioma
o Benign prolif of blood vessels
o Present @ birth, regresses during
childhood***
o Mostly skin (strawberry) and liver
 Angiosarcoma
o Malignant prolif of endothelial cells
o Highly aggressive
o Mostly skin, breast, liver
 Liver angiosarcoma a/w polyvinyl
chloride***, arsenic, Thorotrast
 Kaposi sarcoma
o Low-grade malignant prolif of
endothelial cells
o a/w HHV-8***
o PURPLE patches, plaques and nodules
on skin
o Older Eastern European males 
remains localized to skin
o AIDS or transplant pts  spreads early
ISCHEMIC HEART DISEASE
 o
Stable angina
o Pain w/ exertion or emotional stress
o >70% stenosis
o Chest pain lasting <20 min radiates
to L-arm or jaw
o Subendocardial ischemia  ST
depression
 Unstable angina
o Occurs at rest
o Rupture of plaque w/ thrombosis and
INCOMPLETE occlusion
o Subendocardial ischemia  ST
depression
o High risk of MI
 Prinzmetal angina
o Coronary artery vasospasm
o Transmural ischemia  ST elevation
 Myocardial infarction
o Necrosis of cardiomyocytes
o Rupture of plaque w/ thrombosis and
COMPLETE occlusion
o Severe crushing pain lasting >20 min
o Ventricles involved, atria usually
spared
 Lab tests
o Troponin I = most sensitive and specific
 Rises 2-4 hrs after, peaks 24 hrs,
returns to normal 7-10 days
o CK-MB remains elevated for ~72 hrs
 Reperfusion of irreversibly-damaged cells 
Ca2+ influx  contraction band necrosis
 Free radical generation  reperfusion injury
 Dressler syndrome
o Autoimmune pericarditis 6-8 wks after
transmural MI (Abs against
pericardium)
CHRONIC HEART FAILURE
 Left-sided CHF
o ↓CO
 Reduced BF to kidneys  ↑RAAS
 fluid retention exacerbates
CHF
o Pulmonary congestion  pulm edema
 Dyspnea, PND, orthopnea,
crackles
 Intra-alveolar hemorrhage 
hemosiderin-laden macrophages
 Right-sided CHF
o Systemic congestion
 Elevated JVP
 Painful hepatosplenomegaly w/
“nutmeg” liver***
 Dependent pitting edema
CONGENITAL CARDIAC DEFECTS
 VSD
o MOST COMMON
o a/w fetal alcohol syndrome
o L  R shunt  pulm HTN  reverses
(Eisenmenger syndrome)
 ASD
o MC due to ostium secundum
o Ostium primum is a/w Down’s***
o S2, paradoxical emboli
 PDA
o a/w congenital rubella***
o LR shunt  Eisenmenger syndrome
 cyanosis in LOWER extremities
o Holosystolic “machine-like” murmur
o PGE keeps PDA open  indomethacin
reduces PGE to close PDA
 Tetralogy of fallot
o Stenosis of RV outflow tract
o RV hypertrophy
o VSD
o Aorta overriding VSD
o RL shunt***  early cyanosis
o Squatting increases SVR  decreases
shunting to allow more blood to reach
lungs
o Boot-shaped heart on x-ray***
 Transposition of the great vessels
o 2 independent circuits that do not mix
o a/w maternal diabetes***
o Need to maintain PDA to survive
 Truncus arteriosus
o Single large vessel stemming from both
ventricles (truncus fails to divide)
o Early cyanosis (blood from RV mixes
with blood from LV)***
 Tricuspid atresia
o Tricuspid valve orifice fails to develop
 RV hypoplasia
o a/w ASD
o RL shunt  early cyanosis***
 Coarctation of the aorta
o Infantile a/w PDA
 Distal to arch but proximal to
PDA
 Lower extremity cyanosis
 a/w Turner syndrome***
o Adult
 Distal to arch
 BP in upper >> lower extremities
 Collaterals thru the intercostals
 notching of ribs***
 a/w bicuspid aortic valve
VALVULAR DISORDERS
 Acute rheumatic fever (GAS strep)
o M protein resembles human tissues 
molecular mimicry***
o ASO and anti-DNase B titers
o Criteria:
 Joint
 O (heart – pancarditis)
 Nodules in skin
 Erythema marginatum
 Sydenham chorea
o Endocarditis – MV > AV
 Small vegetations along lines of
closure  regurgitation
o Myocarditis
 Aschoff bodies = chronic
inflammation with
fibronoid/giant cells
 Anitschkow cells = histiocytes w/
wavy nuclei
Pericarditis  friction rub & chest pain
 Chronic rheumatic heart disease
o Repeat exposure to GAS
o Scarring  stenosis
 Thickening of chordae tendineae
and cusps of MV
 Fusion of commissures of AV***
 fish-mouth
o Complication = endocarditis
 Aortic stenosis
 o Fibrosis and calcification  disease of
“wear and tear”
o Increased risk with bicuspid valve
o If rheumatic etiology
 MV will also be involved
 Fused AV commissures
o Sys crescendo-decrescendo murmur
o Complications: concentric LVH, angina,
syncope, microangiopathic hemolytic
anemia
 Aortic regurgitation
o MC due to dilated aortic root
o Early, blowing diastolic murmur
o Hyperdynamic circulation, wide pulse
pressure (↑sys, ↓dias)
o Bounding pulse, pulsating nail bed
(Quincke), head bobbing
o LV dilation and eccentric hypertrophy
 Mitral valve prolapse
o Seen in 2-3% of US adults
o Due to myxoid degeneration  floppy
o May be a/w CT d/o
o Mid-systolic click +/- regurg murmur
o Rare complications due to valve dmg
 Mitral regurgitation
o Complication of MVP, acute rheumatic
heart dz, papillary muscle rupture
o Holosystolic “blowing” murmur
o Complications: volume overload and L-
sided CHF
 Mitral stenosis
o Chronic rheumatic valve disease
o Opening snap + diastolic rumble
o Pulmonary congestion, pulmonary HTN
o (LA dilatation)  atrial fibrillation, risk
mural thrombi
ENDOCARDITIS
 MCC by Strep viridans – infects previously
damaged valves (i.e. chronic rheumatic)
o Small vegetations that do NOT destroy
valves
 Staph aureus = MC in IVDUs
o Affects normal valves (tricuspid)
o Large vegetations that destroy the
valve
 Strep epidermidis – a/w prosthetic valves
 Strep bovis – a/w underlying colorectal CA
 Sterile vegetations
o a/w hypercoagulable or underlying CA
o often involve MV
 Libman-Sacks endocarditis
o Sterile vegetations a/w SLE
o Present on surface + undersurface***
of MV  MR
CARDIOMYOPATHY
 Dilated CM
o SYSTOLIC dysfunc  biventricular CHF
o MR and TR
o Simultaneous onset of R and L-sided
congestion
o a/w coxsackie A/B myocarditis,
pregnancy, doxorubicin
 Hypertrophic CM
o DIASTOLIC dysfunc
o ↓CO, sudden death in young
athletes***, syncope w/ exercise
o Myofiber hypertrophy + disarray***
o a/w genetic mutations in sarcomere
proteins (AD)
 Restrictive CM
o DIASTOLIC dysfunc
o Amyloidosis, sarcoidosis,
hemochromatosis, endocardial
elastosis (children), Loeffler syndrome
(endomyo fibrosis w/ eosinophilic
infiltrate)
o Low-voltage EKG + diminished QRS
amplitude
CARDIAC TUMORS
 Myxoma
o MC primary cardiac tumor in adults
o Benign mesenchymal tumor
o Gelatinous appearance (lots of ground
substance)
o Forms pedunculated mass in LA 
syncope and obstruction of MV
 Rhabdomyoma
o MC primary cardiac tumor in children
o a/w tuberous sclerosis***
o Benign hamartoma
o Usually arises in ventricle
 Metastasis
o More common than primary tumors
o Come from breast, lung, melanoma,
lymphoma
o Mostly involve pericardium 
pericardial effusion
NASOPHARYNX
 Rhinitis
o MCC = adenovirus
o Sneezing, congestion, runny nose
o Allergic rhinitis = type I HSR
 Eosinophils
 a/w asthma and eczema

Nasal polyps
o Protrusions of edematous, inflamed
nasal mucosa
o Repeated bouts of rhinitis (cystic
fibrosis***, ASA-intolerant asthma***)
 Angiofibroma
o Benign tumor of nasal mucosa
 Large blood vessels + fibrous
tissues
o Adolescent males*** w/ perfuse
epistaxis
 Nasopharyngeal carcinoma
o Malignant tumor of nasal mucosa
 a/w EBV***
o African children & Chinese adults
o Pleomorphic keratin-positive***
epithelial cells + lymphocytes
o Often involves cervical lymph nodes
LARYNX
 Acute epiglottitis
o MCC = H. influenzae type b***
o High fever, sore throat, drooling w/
dysphagia***, muffled voice,
inspiratory stridor
o Risk airway obstruction
 Laryngotracheobronchitis (croup)
o MCC = parainfluenza virus***
o Hoarse, “barking” cough***,
inspiratory stridor
 Vocal cord nodule (singer’s nodule)
o Nodule on true vocal cord
o Excessive use of vocal cords (bilateral*)
o Myxoid degeneration
o Hoarseness, resolves with rest
 Laryngeal papilloma
o Benign papillary tumor of vocal cord
o HPV 6, 11***
o Single in adults, multiple in children
o Hoarseness
 Laryngeal carcinoma
o SCC from epithelial lining of vocal cord
o Risk factors = smoking, alcohol***
o Rarely arise from laryngeal papilloma
o Hoarseness, cough, stridor
PULMONARY INFECTIONS (pleuritic chest pain)
 Lobar pneumonia
o Consolidation of entire lobe
o MCC: S pneumo (95%), K pneumo***
o Congestion
o Red hepatization
o Gray hepatization
o Resolution – type II pneumocytes
 Bronchopneumonia
o Scattered patchy consolidation
centered around bronchioles
o Often multifocal and bilateral
 Interstitial (atypical) pneumonia
o Diffuse interstitial infiltrates
o Relative mild URT symptoms
o “atypical” presentation
 Aspiration pneumonia
o Alcoholics, comatose pts
o MCC = anaerobic bacteria of
oropharynx (Bacteroides,
Fusobacterium, Peptococcus)
o Mostly R-lower lobe abscess***
  R-main stem has less angle
 Tuberculosis (AFB+)
o Primary TB
 Ghon complex = LOWER lobe
caseating necrosis + hilar lymph
node (fibrosis and calcification)
 Mostly asymp, but has +PPD
o Secondary TB
 Reactivation a/w AIDS and aging
 Occurs in UPPER lobes
 Cavitary foci of caseous necrosis
 May also lead to military
pulmonary TB or tuberculous
bronchopneumonia
 Fever, night sweats, hemoptysis,
weight loss
 Systemic spread can involve:
meninges, cervical lymph nodes,
kidney, lumbar vertebrae (Pott
dz)
CHRONIC OBSTRUCTIVE PULMONAR DZ
 Chronic bronchitis
o Productive cough lasting at least 3 mos
over minimum of 2 yrs
o Highly a/w smoking
o Hypertrophy of bronchial mucinous
glands  ↑Reid index
o Mucus plugs trap CO2 (↑PaCO2***)
o “BLUE BLOATERS”
o Increased infection, cor pulmonale
 Emphysema
o Destruction of alveolar air sacs  loss
of elastic recoil and collapse during
exhalation  air trapping
o Imbalance of proteases vs
antiproteases
o Smoking = MCC of emphysema
 ↑↑protease activity
 Centriacinar (end alveoli sacs
spared), worst in UPPER lobes
o A1AT deficiency
 ↓antiprotease
 Panacinar, worst in LOWER lobes
 Normal = PiMM
 Disease = PiZZ  misfolding of
protein  accumulation in ER of
LIVER  liver cirrhosis
 PAS+ globules***
o “PINK PUFFERS”
o Pursed-lip breathing  ↑back pr
o ↑AP diameter of chest (barrel-chest)
o ↑FRC
o Hypoxemia (↓DLCO, surface area) and
cor pulmonale
 Asthma
o REVERSIBLE airway
bronchoconstriction
o Type I HSR, a/w allergic rhinitis and
eczema
o Th2  IL-4, IL-5, IL-10
 IL-4  switch to IgE
 IL-5  recruit eosinophils
 IL-10  enhance Th2
o Early  histamine vasodilation &
vascular permeability
o 2nd phase  leukotrienes 
vasoconstriction, bronchoconstriction,
vascular permeability
o Late phase – major basic protein
perpetuates bronchoconstriction
o Productive cough: Curschmann spirals
+ Charcot-Leyden crystals***
(eosinophils)
o ASA-intolerant asthma – asthma,
bronchospasm, nasal polyps
 Bronchiectasis
o Permanent DILATION of bronchioles
and bronchi (loss of tone)
o a/w necrotizing inflammation: CF,
Kartagener syndrome (dynein arm
defect), tumor, necrotizing infection,
allergic bronchopulmonary
aspergillosis (a/w asthma and CF)
o Foul-smelling sputum***
o Hypoxia and cor pulmonale
o Secondary amyloidosis*** due to
chronic inflammation (SAA  AA)
RESTRICTIVE DISEASES
 Idiopathic pulmonary fibrosis
o TGF-β from injured pneumocytes
o Secondary causes: bleomycin and
amiodarone
o Subpleural patches  honeycomb
 Pneumoconiosis
o Alveolar macrophages engulf foreign
particles  induce fibrosis
o CWP – carbon dust, BLACK lungs
 a/w RA (Caplan syndrome)
o Silicosis – upper lobe fibrotic nodules
 ↑risk of TB* (↓phagolysosome)
o Berylliosis – look like sarcoidosis
 ↑risk of lung cancer
o Asbestosis – fibrous plaques
 ↑↑risk of lung cancer***
 ↑risk mesothelioma***
 Sarcoidosis
o NONCASEATING granulomas in
multiple organs
o Classically in Af-Am females
o a/w CD4+ T-cell activity
o involve hilar lymph nodes and lung 
restrictive dz
o stellate inclusions = asteroid bodies***
o may also have: uveitis, cutaneous
nodules, erythema nodosum, Sjogren-
like syndrome
o elevated serum ACE
o hyperCa2+*** (1α-hydroxylase of
epithelioid histiocytes activates vitD)
 Hypersensitivity pneumonitis
o Granulomatous reaction to inhaled
organic antigens (pigeon breeders)
o FEVER, cough, dyspnea hours after
exposure
o Chronic exposure  interstitial fibrosis
PULMONARY HTN
 Primary
o Young adult females
o Familial: BMPR2 mutation***  prolif
of vascular smooth muscle
 Secondary
o Hypoxemia (COPD)
o ↑volume (congenital heart dz)
o Recurrent pulmonary embolism
 Atherosclerosis of pulmonary trunk
 Smooth muscle hypertrophy + intimal
fibrosis
 Plexiform lesions***
 Presents w/ exhertional dyspnea***
 Eventual cor pulmonale
RESPIRATORY DISTRESS SYNDROMES
 Acute respiratory distress syndrome
o Damage  exudate  hyaline
membrane
o ↑DLCO  hypoxemia and cyanosis
o ↑surface tension  alveolar collapse
o Diffuse whiteout of lung***
o Activation of PMNs and protease
damage of type I + II*** pneumocytes
o Knock out type II  interstitial fibrosis
 Neonatal respiratory distress syndrome
o ↓surfactant production from type II
o ↑respiratory effort after birth, use of
accessory muscles
o Diffuse granularity of lung
o a/w prematurity (screen L:S ratio > 2 =
mature lung), C-section (lack cortisol),
maternal diabetes (insulin inhibits
production of surfactant)
o hypoxemia  ↑risk of PDA and
necrotizing enterocolitis
o O2 supplement  blindness and
bronchopulmonary dysplasia
LUNG CANCERS
 Benign lesions
o Granuloma (TB, fungi)
o Bronchial hamartoma = lung tissue +
cartilage*** (calcified)
 Small cell carcinoma (15%)
o Tx with chemo
o Poorly differentiated neuroendocrine
cells (Kulchitsky cells)
o Male smokers
 o CENTRAL lesions
o ↑ADH or ACTH
o Eaton-Lambert syndrome
 Non-small cell carcinoma (85%)
o Tx surgically
o AdenoCA – glands + mucin
 MC tumor in non-smokers or
female smokers
 PERIPHERAL
o SCC – keratin pearls
 MC tumor in male smokers
 CENTRAL
 May produce PTH  hyperCa2+
o Large cell carcinoma – no glands or
keratin
 a/w smoking, poor prognosis
 Carcinoid tumor
o Well-differentiated neuroendocrine
cells (form nests)
o Chromogranin+***
o Forms polyp-like mass in bronchus
o NOT related to smoking
o May cause carcinoid syndrome
 Bronchioloavleolar carcinoma
o Columnar cells along bronchioles
o Arise from Clara cells***
o NOT related to smoking
o PERIPHERAL
o Present w/ pneumonia-like
consolidation on x-ray***
o Good prognosis
 Metastasis to lung
o More common than primary
o MC sources = breast and colon
o Multiple nodules
 Adrenal gland = unique site of distant spread
LUNG PLEURA
 Pneumothorax
o Spontaneous – rupture of blebs
 Young adults
 Collapse of lung
 Trachea pulled to side of collapse
o Tension – penetrating chest injury
 Trachea pushed to OPPOSITE side
of collapse
 Mesothelioma
o Malignant neoplasm a/w asbestos
o Recurrent pleural effusions, dyspnea,
chest pain
o Tumor encases the lung
ORAL CAVITY
 Cleft lip/palate
o Failure of facial prominence fusion*
o Usually occur together
 Aphthous ulcer
o Painful ulcer a/w stress
o Resolves but recurs
o Grayish base surrounded by erythema
 Behcet syndrome
o Recurrent aphthous ulcers, genital
ulcers and uveitis
o a/w immune complex vasculitis
 Oral herpes
o Vesicles rupture  ulcers
o a/w HSV-1
o remains latent in trigeminal nerve
ganglia***
o “cold sores”
 SCC
o Risk factors = smoking, alcohol
o MC location = floor of mouth
o Leukoplakia (not scraped off)
o Erythroplakia
 Hairy leukoplakia – on lateral tongue, a/w
AIDS and EBV
o NOT pre-malignant
SALIVARY GLAND
 Mumps
o Bilateral inflammation of parotid
glands
o Orchitis, pancreatitis, aseptic
meningitis
 Sialadenitis
o Unilateral inflammation of salivary
gland
o MC due to obstructing stone  S.
aureus infection
 Pleomorphic adenoma
o MC tumor of salivary gland
o Benign: stromal and epithelial
o MC in parotid  mobile, painless,
circumscribed @ angle of jaw
o High recurrence*** (irregular margin)
o Rare transformation in to carcinoma
 involves facial nerve
 Warthin tumor
o 2nd MC tumor of salivary gland
o Benign CYSTIC tumor
o Lymphocytes + germinal centers
o MC in parotid
 Mucoepidermoid carcinoma
o Malignant tumor of mucinous and
squamous cells
o MC in parotid
o Involves facial nerve  PAIN
ESOPHAGUS
 Tracheoesophageal fistula
o Congenital, MC proximal esophageal
atresia w/ distal esophagus arising
from trachea
o Vomiting, polyhydramnios, abd
distension, aspiration
 Esophageal web
o MC in upper esophagus
o Dysphagia of poorly chewed food
o ↑risk for esophageal SCC
o Plummer-Vinson – iron deficiency
anemia + esophageal web + beefy-red
tongue (atrophic glossitis)
 Zenker diverticulum
o Outpouching through acquired defect
in muscular wall (false)
o Junction of esophagus and pharynx
o Dysphagia, obstruction, halitosis
 Mallory-Weiss syndrome
o Longitudinal laceration at GE junction
o a/w severe vomiting (alcoholism,
bulimia)
o PAINFUL hematemesis
o Risk Boerhaave syndrome – rupture of
esophagus  air in mediastinum 
subQ emphysema (cracking)
 Esophageal varices
o Due to portal HTN – left gastric vein
anastomoses with esophageal vein
o Asymptomatic, but risk rupture 
PAINLESS hematemesis
 Achalasia
o Disorder esophageal motility + inability
to relax LES
o Due to damaged ganglion cells in
myenteric plexus a/w Trypanosoma
cruzi
o Bird-beak sign on barium swallow***
o High LES pressure***
o Dysphagia for solids and fluids
o Putrid breath
o ↑risk of esophageal SCC
 GERD
o Reduced LES tone
o Risk factors: alcohol, smoking, obesity,
fat-rich diet, caffeine, hiatal hernia***
o Heartburn, asthma, enamel dmg
o Late: ulceration w/ stricture or Barrett
 Barrett esophagus
o Stratified squamous  nonciliated
columnar w/ goblet cells
o May progress to dysplasia and
adenoCA
 Esophageal carcinoma
o AdenoCA = MC type of esophageal
carcinoma in the West
 arise from Barrett, involves
LOWER 1/3 of esophagus
o SCC = MC type of esophageal
carcinoma worldwide
 Risk factors: alcohol, smoking,
very hot tea, achalasia, Plummer-
Vinson syndrome, esophageal
injury
 Involves UPPER or MIDDLE 1/3
 Progressive dysphasia***
 Hoarseness, cough
STOMACH
 Gastroschisis
o Anterior abdominal wall malformation
 expose abd contents
 Omphalocele
 o Persistent herniation through umbilical
cord  covered w/ peritoneum and
amnion
 Pyloric stenosis
o Congenital hypertrophy (M > F)
 Born NORMAL, present @ 2wks
o Projectile nonbilious vomit***
o Visible peristalsis
o Olive-like mass in abdomen
 Acute gastritis
o Burning of stomach by acid (↑acid or
↓mucosal protection)
o Severe burns  hypovolemia  ↓BF
 Curling ulcer
o ↑ICP  ↑vagal stimulation  ↑acid
production  Cushing ulcer***
o NSAIDs  ↓PGE2
o Heavy alcohol
o Chemotherapy, shock
 Chronic gastritis
o Chronic autoimmune
 o
Destruction of parietal cells (in
BODY and FUNDUS***) and/or
intrinsic factor
 Type IV HSR
 Mucosal atrophy
 Achlorhydria, ↑gastrin, G-cell
hyperplasia
 MC of pernicious anemia***
 Intestinal metaplasia  ↑risk for
gastric adenoCA
o Chronic H. pylori (90%)
 MC involve ANTRUM***
 Ureases and proteases cause
inflammation and weaken
mucosal defenses
 Pain
 ↑risk for gastric adenoCA and
MALT lymphoma
 Tx: triple therapy
 Peptic ulcer disease
o Duodenal ulcer (90%)
 H. pylori or ZE syndrome
(↑gastrin)
 Pain IMPROVES w/ meals
 Hyperplasia of Brunner’s glands
 Posterior ulcer rupture 
bleeding from gastroduodenal
artery or acute pancreatitis
 Never malignant
o Gastric ulcer (10%)
 H. pylori or NSAIDs
 Pain WORSENS w/ meals
 Rupture along lesser curvature 
bleeding from L-gastric artery
 May be a/w gastric carcinoma
 Gastric carcinoma
o Intestinal type – large, irregular ulcers
w/ heaped up margins
 Lesser curvature
 Risk factors: intestinal
metaplasia, nitrosamines, blood
type A***
o Diffuse type – signet ring cells***
 Desmoplasia  linitis plastic***
 Not a/w intestinal-type risk
factors
 Early satiety
Acanthosis nigricans, Leser-Trelat
(explosion of seborrheic keratosis)
o Can involve Virchow node = LEFT
supraclavicular node
o MC metastasize to liver
o Sister Mary Joseph nodule =
periumbilical (intestinal-type)
o Krukenburg tumor (diffuse type) 
mucin producing, bilateral ovarian
enlargement
SMALL BOWEL
 Duodenal atresia
o a/w Down syndrome***
o Polyhydramnios
o Bilious vomiting
o “double bubble” sign***
 Meckel diverticulum
o Outpouching of all 3 layers (true)
o Due to failure of vitelline duct
involution (midgut connection to yolk
sac)
o No closure  pass meconium through
umbilicus
o Slight closure  Meckel diverticulum
o 2%, 2 inch long, 2 feet down from
ileocecal valve, present within first 2
yrs of life
o Most cases asymp
o Bleeding  ectopic gastric mucosa
 Volvulus
o Twisting  infarction
o Elderly  sigmoid colon
o Young adults  cecum
 Intussusception
o Telescoping of proximal segment into
distal segment
o Children  lymphoid hyperplasia
(Peyer’s patches)
o Adults  tumor
 Small bowel infarction
o Transmural infarction –
embolism/thrombosis of SMA or
thrombosis of mesenteric vein
o Mucosal infarcation – marked
hypotension
 Lactose intolerance
o No lactase in brush border
o Abd distension and osmotic diarrhea
o May be congenital or acquired
o Temporary after small bowel infarction
 Celiac disease
o Blunting of villi due to gluten exposure
 Most prominent in duodenum**
o a/w HLA-DQ2 and DQ8*****
o gliadin gest deamidated by tissue
translglutaminase (tTG)  presented
via MHC II  CD4+ T-cell damage
o Dermatitis herpetiformis (blisters)***
 IgA deposition at tips of dermal
papillae
 Resolves when remove gluten
o IgA against endomysium, tTG or gliadin
o Late complications: small bowel
carcinoma, T-cell lymphoma
 Tropical sprue
o Damage to small bowel villi due to
unknown agent
 Most prominent in jejunum and
ileum***
o Arises AFTER infectious diarrhea (abx)
 Whipple disease
o Macrophages loaded with Tropheryma
whippelii
o PAS+ foamy macrophages
o Stuck in lamina propria  compress
lacteals  chylomicrons cannot enter
lymphatics
o Fat malabsorption and steatorrhea
 Abetalipoproteinemia
o AR deficiency of apo-B48 and B100
o Defective chylomicron formation (B48)
o Absent VLDL and LDL (B100)
 Carcinoid tumor
o Malignant neuroendocrine
o Chromogranin+***
o MC in small bowel
o 5HT  liver MAO breaks it down into
5-HIAA  asymp
o If spread to liver***  bronchospasm,
diarrhea, flushing of skin
o R-sided valvular fibrosis*** (lung has
MAO)
APPENDIX
 Acute appendicitis
o Children  lymphoid hyperplasia
o Adult  fecalith
o Periumbilical pain, fever, nausea
 Pain moves to LRQ (McBurney pt)
o Rupture  guarding and rebound
tenderness
INFLAMMATORY BOWEL DISEASE
 Young adults w/ recurrent bouts of BLOODY
diarrhea and abd pain
 Most prevalent in Caucasians and Eastern
European Jews
 Crohn disease
o Transmural
o Skip lesions, MC terminal ileum
o RLQ pain, non-bloody diarrhea
 o Granulomas
o Cobblestone mucosa, creeping fat
o Strictures  “string sign”
o Malabsorption w/ nutritional
deficiencies
o Fistula formation***
o If involve colon  then there is a risk
for carcinoma
o Ankylosing spondylitis, polyarthritis,
erythema nodosum
o Smoking ↑risk
 Ulcerative colitis
o Mucosal or submucosal
o Continuous, starts @ rectum
o LLQ pain, bloody diarrhea
o Crypt abscesses, pseudopolyps
o Loss of haustra  “lead pipe” sign
o Toxic megacolon and carcinoma risk
o Primary sclerosing cholangitis***
o p-ANCA+***
o Smoking is protective
COLON
 Hirschprung disease
o Failure of relaxation and peristalsis of
distal sigmoid and rectum
o a/w Down syndrome
o Failure of ganglion cells to descend
into myenteric and submucosal plexus
o Myenteric (Auerbach) btw IC and OL
muscle layers
o Submucosal (Meissner) regulates BF,
secretions and absorption
o Failure to mass meconium
o Empty rectal vault
o Massive dilatation  megacolon
proximal to obstruction
o Need rectal suction biopsy*** to
include submucosa
o Resect involved bowel
 Colonic diverticula (high stress on LEFT)
o Outpouching through muscularis
propria (false)
o MC location = sigmoid colon
o Related to wall stress: constipation,
straining, low-fiber diet
o Areas where vasra recta traverse
(weak point)
o Hematochezia, diverticulitis (LLQ pain),
fistula (air or stool in urine)
 Angiodysplasia (high stress on RIGHT)
o Acquired
o Mostly in cecum and right colon
o High wall tension
o Hematochezia in older adult
 Hereditary hemorrhagic telangiectasia
o AD
o Thin-walled vessels in mouth and GI
tract  rupture  bleeding
 Ischemic colitis
o MC at splenic flexure
o a/w atherosclerosis of SMA
o Postprandial pain and weight loss
o May have bloody diarrhea
 Irritable bowel syndrome
o Middle-aged females
o Relieved w/ defecation
o No pathologic changes
 Colonic polyps
o Hyperplastic glands
 MC in rectosigmoid (L-side)
 Serrated appearance***
 Benign, no malignant potential
o Neoplastic proliferation
 Benign, but premalignant
 May progress to adenoCA
o Adenoma-carcinoma sequence
 APC mutation
 K-ras mutation
 p53 mutation  increases COX
expression (ASA is protective***)
o Greatest risks  >2 cm, sessile, villous
 Familial adenomatous polyposis
o AD, loss of APC on chromo 5***
o 100s-1000s of polyps
o High risk of carcinoma
o Gardner syndrome = FAP +
fibromatosis and osteomas
o Turcot syndrome = FAP + CNS tumors
 Juvenile polyp
o Sporadic hamartomatous polyps in
children <5 yrs
o Solitary rectal polyp  prolapses and
bleeds
 Peutz-Jeghers syndrome
o AD
o Hamartomatous polyps through GI
tract
o Mucocutaneous hyperpigmentation of
lips, oral mucosa, and genital skin***
o ↑risk for colorectal, breast and GYN
cancer
 Colorectal carcinoma
o 3rd MCC cancer incidence and death
o Adenoma-carcinoma sequence (APC)
or microsatellite instability (MSI)
o Hereditary nonpolyposis carcinoma
(HNPCC) – mutations in DNA mismatch
repair enzymes
 ↑risk for colorectal, ovarian and
endometrial CA
o APC  Left-sided – napkin ring lesion
 Decreased stool caliber
o MSI  Right-sided – raised lesion
 Occult bleeding
EXOCRINE PANCREAS
 Annular pancreas
o Ventral pancreas forms ring around
duodenum  obstruction
 Acute pancreatitis
o Premature activation of trypsin*** 
activates other pancreaticenzymes 
autodigestion
o Liquifactive necrosis
o Fat necrosis  saponification
o MCC = alcohol and gallstones 
contract/obstruct sphincter of Oddi
o Other causes: hyperCa+2, hyperlipid,
drugs, scorpion stings, mumps, rupture
of posterior duodenal ulcer
o Epigastric pain radiates to back
o Periumbilical and flank hemorrhage
o Nausea/vomiting
o ↑lipase (more specific) and amylase
o HypoCa2+ (saponification)
o Complications: shock, pancreatic
pseudocyst (↑amylase), pancreatic
abscess, DIC, ARDS
 Chronic pancreatitis
o Fibrosis of pancreatic parenchyma
o Adults  alcohol
o Children  cystic fibrosis
o Pancreatic insufficiency 
malabsorption and steatorrhea
o Fat soluble vit deficiencies
o Dystrophic calcification
o Secondary DM (late)
o ↑risk of pancreatic CA
 Pancreatic carcinoma
o Arise from pancreatic ducts
o Risk factors: smoking, chronic
pancreatitis
o Pain and weight loss
o If in head  blocks bile duct 
jaundice, pale stool
o If in body or tail  secondary DM
(thin, elderly)
o Trousseau sign = migratory
thrombophlebitis (swelling, erythemia,
tenderness in extremities)
o Serum marker CA 19-9***
o Whipple procedure = removal of head
and neck of pancreas, proximal
duodenum and gallbladder
GALLBLADDER and BILIARY TRACT
 Biliary atresia
o Failure to form extrahepatic biliary
tree  obstruction within 1st 3 mos
o Jaundice (CB) and cirrhosis
 Cholelithiasis (gallstones)
o Supersaturation of cholesterol or
bilirubin
o Decreased phospholipids or bile acids
o Stasis
o Cholesterol – radiolucent, yellow
 Es increases activity of HMG-CoA
reductase
 Clofibrate
  Native American
 Crohn disease
 Cirrhosis
o Bilirubin – radio-opaque, black
 Extravascular hemolysis
 Biliary tract infection (E. coli,
Ascaris, Clonorchis 
deconjugation)
o Most asymp
 Biliary colic
o Waxing and waning RUQ pain
o Gallbladder contracting against stone
o Relieved once stone passes
o May result in acute pancreatitis or
obstructive jaundice
 Acute cholecystitis
o Stone  cystic duct dilatation w/
pressure ischemia, bacterial
overgrowth
o RUQ pain radiating to right scapula***
o Fever, WBCs, serum alkaline
phosphatase
 Chronic cholecystitis
o Chemical irritation
o Rokitansky-Aschoff sign*** (herniation
of gallbladder mucosa into muscular
wall
o RUQ pain after eating
o Late  porcelain gallbladder
(dysmorphic calcification, fibrosis)
 Ascending cholangitis
o Enteric gm- bacteria
o Sepsis, jaundice and abd pain
o ↑incidence w/ choledocholithiasis
(stone in biliary ducts)
 Gallstone ileus
o Gallstone obstructs small bowel
o Fistula formation btw gallbladder and
small bowel (air in biliary tree)
 Gallbladder carcinoma
o adenoCA
o gallstones = major risk factor, esp
when complicated by porcelain
gallbladder***
o cholecystisis in elderly women*
o poor prognosis
LIVER
 Jaundice
o Serum bilirubin > 2.5 mg/dL
o ↑UCB
 Extravascular hemolysis (dark
urine due to urobilinogen)
 Ineffective erythropoiesis
 Physiological jaundice of
newborn – low UGT activity
(phototherapy makes UCB water
soluble)
 Gilbert syndrome – mildly low
UGT activity
 Crigler-Najjar syndrome –
absence of UGT
o ↑CB
 Dubin-Jounson syndrome –
deficiency bilirubin canalicular
transport (dark liver)
 Biliary tract obstruction -
↓urobilinogen, ↑ALP (pruritis
due to bile acids; dark urine due
to CB)
o Viral hepatitis increases CB and UCB
 Viral hepatitis
o ALT > AST***
o Hep A and E  fecal oral
 Acute, no chronic
 Hep E in pregnant women 
fulminant hepatitis
o Hep B  needles, placental
 Acute, rare chronic
o Hepatitis C
 Most chronic
o Hepatitis D
 Requires hep B
o Chronic hepatitis mostly affects portal
tract
 Cirrhosis
o TGF-β from stellate cells (line beneath
endothelial cells that line sinusoids) 
broad bands of fibrosis separating
nodules
o Portal HTN  ascites, congestive
splenomegaly, portosystmic shunts,
hepatorenal syndrome
o ↓detoxicification  mental status
changes, asterixis, gynecomastia,
spider angiomata, palmer erythema
(↑Es), jaundice
o ↓protein synthesis 
hypoalbuminemia, decreased clotting
factor production (↑PT and PTT)
 Alcohol-related liver disease
o AST > ALT*** (AST located in
mitochondria)
o Damage due to acetyladehyde
o Fatty liver
o Mallory bodies (damaged cytokeratin
filaments***)
 Nonalcoholic fatty liver disease
o ALT > AST***
o a/w obesity
 Hemochromatosis
o Iron deposition (hemosiderosis)
o End organ dmg (hemochromatosis)
o Fentin rxn  Fe can generate ROS
o 1⁰  HFE mutation (C282Y)
o 2⁰  transfusions
o Presents in late adulthood
o Classic triad = cirrhosis, 2⁰ DM, bronze
skin
o Cardiac arrhythmia, gonadal
dysfunction
o Prussian stain***
 Wilson disease
o ATP7B gene mutation in ATP-mediated
hepatocyte copper transport  cannot
transport copper into bile or onto
ceruloplasmin
o Copper also generates ROS
o Presents in childhood
 Cirrhosis
 Neurologic (behavioral,
dementia, chorea,
parkinsonism)***
 Kayser-Fleischer rings in
cornea***
o ↑urinary copper, ↓serum
ceroloplasmin***
o Tx: D-penicillamine
 Primary biliary cirrhosis
o Autoimmune granulomatous
destruction
o Women ~40 yrs
o Anti-mitochondrial antibody***
o Obstructive jaundice
o Late: cirrhosis
 Primary sclerosing cholangitis
o Fibrosis of intrahepatic and
extrahepatic bile ducts
o Onion skinning
o “beaded” appearance
o a/w ulcerative colitis (p-ANCA***)
o Obstructive jaundice
o Late: cirrhosis
o ↑risk of cholangiocarcinoma***
 Reye syndrome
o Fulminant liver failure +
encephalopathy
o Children w/ viral illness who take ASA
o Hypoglycemia, ↑LFTs,
nausea/vomiting
[recall: give Kawasaki pts ASA]
 Hepatic adenoma
o Benign tumor of hepatocytes
o a/w OTCs
o risk rupture and intraperitoneal
hemorrhage (esp during pregnancy)
 Hepatocellular carcinoma
o Risk factors = chronic hepatitis,
cirrhosis, aflatoxins from
Aspergillus*** (induce p53 mutations)
o Can develop Budd-Chiari syndrome
 Infarction due to hepatic vein
obstruction
 PAINFUL hepatomegaly and
ascites
o ↑AFP***
 Metastasis to liver
o More common than primary tumors
o MC from colon, pancreas, lung, breast
o Multiple nodules on liver
CONGENITAL KIDNEY DISORDERS
 Horseshoe kidney (MC)
o Conjoined at lower pole
 o Located in lower abd (caught on IMA
root)
 Renal agenesis
o Unilateral  hypertrophy of existing
kidney
 Hyperfiltration  risk renal
failure
o Bilateral  oligohydramnios sequence
 Incompatible with life
 Lung hypoplasia, flat face, low set
ears, Potter sequence
 Dysplastic kidney
o Noninherited**, UNILATERAL
o Cysts and abnormal tissue
 Polycystic kidney disease
o BILATERAL enlarged kidneys w/ cysts in
renal cortex and medulla
o AR – juvenile form  renal failure,
HTN, Potter sequence, congenital
hepatic fibrosis and hepatic cysts
o AD (APKD1, APKD2 genes)– adult form
 cysts develop over time, HTN
(↑RAAS), berry aneurysm***, hepatic
cysts, MVP
 Medullary cystic kidney disease
o AD
o Cysts in medullary collecting ducts***
o Parenchyma fibrosis  shrunken
kidneys***
o Worsens renal failure
ACUTE RENAL FAILURE
 Prerenal azotemia
o ↓RBF  ↑RAAS
o BUN:Cr > 15, FENa <1%, urine osm
>500 mOsm/kg
 Postrenal azotemia
o Obstruction of urinary tract
o At first looks like prerenal, then labs
reversed (tubules don’t work)
 Acute tubular necrosis
o MCC of acute renal failure
o Brown, granular casts
o Labs reversed of prerenal (tubules
don’t work)
o Ischemia  PT and medullar segment
of TAL most susceptible
 Preceeded by prerenal azotemia
o Nephrotoxicity = aminoglycosides,
heavy metals, myoglobinuria, ethylene
glycol, radiocontrast dye, urate (tumor
lysis syndrome***)
o Tubular cells = stable cells  takes a
few days to re-enter cell cycle and
resolve oliguria
 Acute interstitial nephritis
o Drug-induced HSR of interstitium and
tubules
o Inflammation in interstitium, but
tubules are not damaged
o NSAIDss, PCN, diuretics
o Fever, rash after starting drug
o Eosinophils in urine***
o May progress to renal papillary
necrosis
 Renal papillary necrosis
o Hematuria and flank pain
o Causes:
 Chronic analgesics (phenacetin,
ASA)
 DM
 Sickle cell trait/disease
 Server acute pyelonephritis
URINARY TRACT INFECTION
 Cystitis
o Dysuria, urinary frequency, urgency,
suprapubic pain
o MC due to ascending infection
o No systemic signs
o Cloudy urine >10 WBCs/hpf
o Dipstick: positive leylocyte esterase
and nitrites
o E. coli 80%
o Proteus  alkaline urine w/ stones
o Pyuria + negative urine culture 
Chlamydia and Neisseria
 Pyelonephritis
o MC due to ascending infection
o ↑risk w/ vesicoureteral reflux
o Fever, flank pain, WBC casts,
leukocytosis
o E. coli (90%)
 Chronic pyelonephritis
o Vesicoureteral reflux (children) 
scarring at upper/lower poles
o Obstruction (BPH, or cervical CA)
o Thyroidiziation of kidney*****
(proteinaceous material in atrophic
tubules)
NEPHROLITHIASIS
-colicky pain
 Calcium oxalate/calcium phosphate
o MCC stone in adults
o More often due to idiopathic
hyperCa2+
o Tx: thiazides
 Ammonium, magnesium, phosphate
o a/w infection: proteus or klebsiella
o Staghorn calculi***
 Uric acid
o RADIOLLUSCENT
o Hot, acid climates
o Low urine volume
o Acidic pH***
o Tx: hydration and alkalinization***
 Cysteine
o Staghorn calculi in children***
CHRONIC RENAL FAILURE
 End-stage kidney failure
o MCC: DM, HTN, glomerular dz
o Uremia
o Salt/H2O retention
o HyperK+ and met acidosis (AG)
o HypoCa2+ (hyperphosphatemia, low
vitD)
o Renal osteodystrophy – osteitis fibrosa
cystica, osteomalacia, osteoporosis
o Shrunken kidneys w/ cysts when on
dialysis  ↑renal cell CA
RENAL NEOPLASIA
 Angiomyolipoma
o Blood vessels, smooth muscle, adipose
o a/w tuberous sclerosis*****
 Renal cell carcinoma
o Classic triad = hematuria, palpable
mass, flank pain
o Fever, weight loss, paraneoplastic
syndromes** (EPO, renin, PTH, ACTH)
o L-sided varicocele***
o Yellow mass
o MC subtype = clear cell
o Loss of VHL (3p) tumor suppressor 
↑IGF-1  ↑HIF transcription factor
 ↑VEGF, PDGF***
o Sporadic  single tumor in upper lobe
(smoker)
o Hereditary  multiple and bilateral
(Von Hippel-Lindau disease ***=
bilateral renal cell CA and
hemangioblastoma of cerebellum)
o Retroperitoneal lymph nodes
 Wilms tumor
o MC kidney mass in children
o Blastema, primitive tissue
o Large, unilateral flank mass
o Hematuria and HTN
o WT1 mutation
o WAGR syndrome – Wilms tumor,
Aniridia, Genital abnormalities,
mental/motor Retardation
o Beckwith-Weidemann syndrome –
Wilms tumor, neonatal hypoglycemia,
muscular hemihypertrophy,
organomegaly
LOWER URINARY TRACT CARCINOMA
 Urothelial carcinoma
o MC, usually in bladder
o Risk factors: smoking, naphthylamine,
azo dyes, cyclophosphamide,
phenacetin
o PAINLESS hematuria
o Papillary – begins as low-grade
o Flat – high-grade flat lesion (early p53)
o Field defect*** entire urothelium is
mutated  recurrence
 SCC
 o Mostly in bladder
o Stems from squamous metaplasia
o Risk factor: chronic cystitis,
Schistosoma hematobium (Egyptian
male)***, long-standing
nephrolithiasis
 AdenoCA
o Mostly in bladder
o Risk factor: urachal remnant (DOME of
bladder to yolk sac)***, cystitis
glandularis, exstrophy
VULVA
 Bartholin cyst
o Obstruction of gland
o UNILATERAL, painful, cystic lesion in
lower vestibule near vaginal canal
 Condyloma
o MC due to HPV 6, 11***
o Also a/w 2⁰ syphillis
o Koilocytic change
 Lichen sclerosis
o THINNING of epidermis + fibrosis of
dermis
o Leukoplakia parchment-like vulvar skin
o Postmenopausal women
o Benign, slight risk of SCC
 Lichen simplex chronicus
o HYPERPLASIA of vulvar sq epi
o Leukoplakia w/ leathery skin
o a/w chronic irritation and scratching
o Benign, NO risk of SCC
 Vulvar carcinoma
o Presents as leukoplakia
o HPV types 16, 18 (40-50yrs)
 Arises from VIN
 Koilocytes, ↑mitotic figures
o Non-HPV  lichen sclerosis (70-80yrs)
 Long standing inflammation and
irritation
 
Extramammary Paget disease
o Malignant epithelial cells in epidermis
o Erythematous, pruritic, ulcerated
o Keratin+, PAS+***
o Distinguish from melanoma (S100+)
o Less CA than Paget’s of nipple
VAGINA
-non-keratinized sq epi
 Adenosis
o Persistence of columnar epithelium in
upper 1/3 of vagina (derived from
Mullerian duct)
o a/w exposure to DES in utero*** 
↑risk of clear cell adenoCA
 Clear cell adenoCA
o Complication of pts exposed to DES w/
adenoma
 Embryonal rhabdomyosarcoma
o Immature skeletal muscle
o Bleeding botyroid mass*** protruding
from vagina or penis
o Children <5 yrs
o Cross-striations, positive for desmin
and myoglobin***
 Vaginal carcinoma (SCC)
o High-risk HPV: 16, 18, 31, 33
o Precursor of VAIN
o Cancer from lower 2/3  inguinal
nodes
o Cancer from upper 1/3  regional iliac
nodes
CERVIX
-exocervix: non-keratinized sq epi
-endocervix: single layer of columnar
-lesions most common @ transformational
junction
 HPV
o High-risk HPV
 E6  inhibits p53***
 E7  inhibits Rb***
Cervical intraepithelial neoplasia (CIN)
o Dysplasia is REVERSIBLE
o Carcinoma is NOT
 Cervical carcinoma
o Middle aged women
o Vaginal bleeding (esp postcoital) or
cervical discharge
o Secondary risk factors: smoking,
immunodeficiency***
o SCC (80%) – a/w HPV
o adenoCA (15%) – a/w HPV***
o advanced tumors can invade through
anterior uterine wall to bladder 
block ureters
o Hydronephrosis w/ postrenal
failure*** = MCC of death
 Screening and prevention
o Pap smear – limited efficacy in
screening of adenoCA
o Colposcopy and biopsy
ENDOMETRIUM and MYOMETRIUM
 Asherman syndrome
o 2⁰ amenorrhea due to loss of
basalis*** and scarring
o a/w overaggressive dilation and
curettage
 Anovulatory cycle
o Estrogen-driven prolif phase w/o
subsequent progresterone-driven
secretory phase
o Proliferative glands break down and
shed  uterine bleeding
o Common cause of dysfunctional
uterine bleeding (esp during menarche
and menopause)
 Acute endometritis
o Bacterial infection
o a/w retained products of conception
o fever, abnormal uterine bleeding,
pelvic pain
 Chronic endometritis
o Lymphocytes and plasma cells***
o Retained produces, chronic PID, IUD,
and TB
o Abnormal uterine bleeding, pelvic
pain, INFERTILITY
 Endometrial polyp
o Hyperplastic protrusion of
endometrium
o Abnormal uterine bleeding
o May be due to tamoxifen*** (pro-
estrogenic effects in endometrium)
 Endometriosis
o Endometrial glands + stroma outside of
uterine endometrial lining
o a/w retrograde menstruation
o dysmenorrhea (pain), pelvic pain,
infertility
o cycles like endometrium
o MC involves OVARY  chocolate cyst*
o Involvement of soft tissue  “gun-
powder” nodules
o ↑risk of carcinoma (esp ovary)
 Adenomyosis
o Endomtriosis that involves the
myometrium
 Endometrial hyperplasia
o Glands > stroma  back-to-back
glands***
o Unopposed ESTROGEN
o Postmenopausal uterine bleeding
(stopped progesterone, but obesity
can produce Es)
o Classified histiologically – most
important predictor for progression to
carcinoma = cellular atypia***
 Endometrial carcinoma
o Malignant prolif of endometrial glands
o Postmenopausal bleeding
o Hyperplasia (50s, endometrioid) or
sporadic (>70, p53***, papillary
serous, psammoma body, aggressive)
 Leiomyoma (fibroids)
o Benign prolif of smooth muscle
o MC tumor in female
o a/w estrogen
o Premenopausal women
o Enlarge during pregnancy, shrink after
o Multiple, well-defined, white
WHORLED masses***
o Usually asymp***
 Leiomyosarcoma
o Malignant prolif of smooth muscle
 o Arises DE NOVO*** (not from
leiomyoma)
o Postmenopausal women
o Single w/ necrosis and hemorrhage
o Mitotic activity, cellular atypia
OVARY
 Polycystic ovarian disease
o Hormonal imbalance
o LH:FSH > 2***
o LH  excess androgen production 
hirsutism
o Androgen converted into estrone (E1)
 inhibitory feedback on FSH
o Reduced FSH  degeneration of
follicle  cyst***
o High levels of estrone  ↑risk for
endometrial CA
o Classic presentation*** = obese young
woman w/ infertility, oligomenorrhea
and hirsutism
o Some pts have insulin resistance and
develop type 2 DM 10-15 yrs later
Surface epithelial tumors (70%)
-coelomic epithelium lines ovaries
-usually cystic
 Serous tumors – filled w/ water
 Mucinous tumors – filled w/ mucus
 Benign form = cystadenoma
o Single cyst w/ simple, flat lining
o MC premenopausal (30-40yrs)
 Malignant form = cystadenocarcinoma
o Complex cysts w/ thick shaggy lining
o MC postmenopausal (60-70yrs)
 Borderline tumors – btw benign and
malignant, have metastatic potential
 BRCA1  ↑risk of serous CA of ovary and
fallopian tube
 Endometrioid tumors – endometrial-like
glands
o Malignant
o May arise from endometriosis
o 15% are independent and a/w
endometrial carcinoma
 Brenner tumor – bladder-like epithelium
o Benign
 Surface tumors present LATE
o Vague abd symps (pain, fullness)
o Signs of compression (urinary freq)
o Poor prognosis
o Spread locally  peritoneum
 CA-125*** = useful serum marker to
monitor for treatment and screen for
recurrence
Germ cell tumors (15%)
-reproductive age (15-30 yrs)
 Cystic teratoma
o Embryological layers
o MC germ cell in females
o 10% bilateral
o Benign
o But presence of immature tissue
(neuroectoderm) or somatic
malignancy (SCC)  indicates
malignant potential
o Struma ovarii = teratoma composed of
thyroid tissue
 Dysgerminoma
o Large cells w/ clear cytoplasm and
central nuclei (looks like ova)
o MC malignant germ cell tumor
o ↑LDH***
 Endodermal sinus tumor
o From yolk sac
o MC germ cell tumor in CHILDREN
o AFP+***
o Schiller-Duval bodies – glomeruloid-
like structures***
 Choriocarcinoma
o Placental tissue, NO villi
o β-hCG***
o Early hematogenous spread
o POOR response to chemo*
 Embryonal carcinoma
o Malignant tumor composed of large
primitive cells
o Aggressive w/ early metastasis
Sex cord-stromal tumors
 Granulosa-theca cell tumor
o Produce estrogen  Es excess
o Prior to puberty  precocious puberty
o Reproductive age  menorrhagia or
metrorrhagia
o Postmenopause (MC)  endometrial
hyperplasia w/ postmenopausal bleed
o Malignant, but low risk for metastasis
 Sertoli-Leydig cell tumor
o Leydig cells have Reinke crystals***
o May produce androgen  hirsutism
and virilization
 Fibroma
o Benign tumor of fibroblasts
o a/w pleural effusions and ascites
(Meigs syndrome***)
Metastasis
 Kruckenburg tumor
o Mucinous tumor in both ovaries
o From signet cell gastric CA
 Pseudomyxoma peritonei
o Mucinous tumor from appendiz
o “Jelly belly”
GESTATIONAL PATHOLOGY
 Ectopic pregnancy
o MC in fallopian tube
o Risk factor = scarring
o Lower quadrant abd pain weeks after
missed period  pregnancy test
 Spontaneous abortion
o <20 weeks gestation
o Up to ¼ of recognizable pregnancy
o Vaginal bleeding, cramp-like pain,
passage of fetal tissue
o MC due to chromosomal abnormalities
o Hypercoaguable states (SLE),
congenital infection, exposure to
teratogens
o 1st 2 weeks of gestation  sAB
o Weeks 3-8  organ malformation
o Months 3-9  organ hypoplasia
 Placenta previa
o Placenta overlies cervical OS
o 3rd trimester bleeding
o Need C-section
 Placental abruption
o Separation of placenta rom decidua
prior to delivery
o Common cause of still birth
o 3rd trimester bleeding and fetal insuff
 Placental accreta
o Improper implantation of placenta into
myometrium w/ little or no intervening
decidua
o Difficult delivery of placenta and
postpartum bleeding
 Preeclampsia
o Pregnancy-induced HTN, proteinuria
and edema
o Arises in 3rd trimester
o Due to abnormality of maternal-fetal
vascular interface in placenta
o May have fibrinoid necrosis
 Eclampsia = preeclampsia + seizures
 HELLP = preeclampsia + thrombotic
microangiopathy involving the liver
 Both HELLP and elcampsia warrant
immediate delivery
 SIDS
o Death of HEALTHY infant 1 month – 1
year w/o cause
o Usually expire during sleep
o a/w sleeping on stomach and smoking
in house
 Hydatidiform mole
o Partial – normal ovum + 2 sperm 
trisomy
 Have fetal tissue
 Some hydropic, some normal villi
 Focal trophoblastic prolif
 Minimal risk of chorioCA
o Complete – empty ovum + 2 sperm 
disomy
 No fetal tissue
 Most villi hydropic
 Diffuse, circumferential
trophoblastic prolif
 2-3% risk of chorioCA
o Passage of grape-like masses through
vaginal canal in 2nd trimester
o Uterus enlarges
o β-hCG much higher than expected***
o “snow storm” U/S finding + lack of
fetal heart sounds
o Screen for development of chorioCA
(β-hCG)
 chorioCA from gestation pathway
respond well to chemo***
  chorioCA from germ cell do NOT
respond well to chemo***
PENIS
 Hypospadias
o Ventral opening
o Failure of urethral folds to close
 Epispadias
o Dorsal opening
o Abnormal positioning of genital
tubercle
o a/w bladder exstrophy
 Condyloma acuminatum
o HPV type 6, 11 w/ koilocytes
 Lymphogranuloma venereum
o Necrotizing granulomatous
inflammation of inguinal lymphatics
and lymph nodes
o STD: Chlamydia serotypes L1-L3
 SCC
o 2/3 cases due to high-risk HPV
o Lack of circumcision
o Precursor in situ lesions:
 Bowen dz – in situ CA of penile
shaft or scrotum (leukoplakia)
 Erythroplasia of Queyrat – in situ
CA of glans (erythroplakia)
 Bowenoid papulosis – in situ CA
that presents as multiple reddish
papules
 Seen in younger pts (40s)
 Do NOT progress to invasive
carcinoma
TESTICLE
 Cryptorchidism
o MC congenital male repro abnormality
o Most resolve spontaneously
o Orchiplexy if not resolved by age 2 –
maintain fertility
o ↑risk of atrophy/infertility and
seminoma
 Orchitis
o Chlamydia D-K or Neisseria
 Younger sexually active
o E. coli or pseudomonas
 Older adults
o Mumps virus
 Teen males (>10 yrs)
 Involves parotid, meninges,
pancreas, testicles
o Autoimmune orchitis
 Granulomas in seminiferous
tubes (not necrotizing like TB)
 Testicular torsion
o Twisting  obstruct thin-walled VEINS
 congestion and hemorrhage infarct
o a/w failure of testes to attach to inner
lining of scrotum
o Testicular pain
o Absent cremasteric reflex***
 Varicocele
o Dilation of spermatic vein due to
impaired drainage
o “bag of worms”
o Mostly L-sided
o a/w renal cell CA
o 
causes infertility
 Hydrocele
o Fluid collection within tunica vaginalis
o a/w incomplete closure of processus
vaginalis
o infants  communication w/
peritoneal cavity
o adults  blockage of lymphatic
drainage
o scrotal swelling that transilluminates
Germ cell tumors (>95%)
-risk factors: cryptorchidism, Klinefelter
 Seminoma (55%)
o Response WELL to radiotherapy***
o Malignant tumor w/ large cells w/
clear cytoplasm and central nuclei
o Forms homogenous mass (NO
hemorrhage or necrosis***)
o Rarely produce β-hCG
 Non-seminoma
o Embryonal CA
 Malignant tumor of primitive
cells (form glands***)
 Hemorrhage mass and necrosis
 Aggressive w/ early
hemotogenous spread
 CTX may result in differentiation
into teratoma***
 AFP or β-hCG
o Endodermal sinus
 MC testicular tumor in children**
 AFP+***
 Schiller-Duval body
o Choriocarcinoma
 NO villi
 Spread early via blood
 β-hCG  similar to FSH, LH and
TSH  can leady to
hyperthyroidism and
gynecomastia***
 Small primary, larger secondary
tumors
o Teratoma
 Malignant in adults
 Benign in children < 12yrs
AFP or β-hCG
o Mixed germ cell tumors
 Prognosis based on worst
component
Sex cord-stromal tumors （benign）
 Leydig cell tumor
o Produce androgens***
o Reinke crystals***
o Precocious puberty in children
o Gynecomastia in adults
 Sertoli cell tumor
o Tubules, clinically silent
Lymphoma
 MCC testicular mass in males > 60 yrs***
 Bilateral, diffuse B-cell type
PROSTATE
 Acute prostatitis
o Chlamydia, Neisseria – young adults
o E. coli and Pseudomonas – older
o Dysuria w/ fever and chills
o Tender and boggy on DRE
o WBCs and bacterial culture
 Chronic prostatitis
o Dysuria w/ pelvic or back pain
o WBCs, but NEGATIVE cultures***
 Benign prostatic hyperplasia
o Hyperplasia of stroma and glands
o Age-related
o NO increased risk of CA
o Related to DHT
o Affects central periurethral zone of
prostate***  obstructive symps:
difficulty starting/stopping steram,
impaired bladder emptying, dribbling
o Hypertrophy of bladder wall,
microscropic hematuria
o PSA slightly elevated (4-10)
o Hydronephrosis
 Prostate adenoCA
o Malignant proliferation of prostatic
glands
o MC cancer in men (incidence)
o Risk factors: age, Af-Am > white >
Asian, diet high in saturated fats
o Affects peripheral, posterior region***
o Nuclei w/ dark nucleoli***
o Often clinically silent  need to screen
(DRE and PSA > 10)
 Reduced free PSA
o Biopsy to confirm presence of CA
o Gleason grading – based on
architecture alone
o Metastasis to lumbar vertebrae*** 
osteoblastic metastases  sclerotic
(↑alkaline phosphatase, PSA, PAP)
o Prostatectomy – local
o Continuous GnRH
o Androgen receptor inhibitor
(flutamide)
ANTERIOR PITUITARY GLAND
 Pituitary adenoma
o Benign tumor of anterior pituitary
o Functional or non-functional
o Mass effect: bitemporal hemianopsia,
hypopituitism, headache
 o Prolactinoma (MC)  galactorrhea and
amenorrhea (females); decreased
libido and headaches (males)
o Growth hormone cell adenoma
 Gigantism – children
 Acromegaly – adults (growth of
organs  dysfunction)
 #1 cause of death = CHF
 GH induces liver gluconeogenesis
 secondary DM
 ↑GH and IGF-1
 Lack GH suppression w/ oral glc
 Tx: octreotide, GH antag, surgery
o ACTH adenomas  Cushing syndrome
o TSH, LH, FSH adenomas are rare
 Hypopituitarism
o Loss of >75% of parenchyma
o Causes:
o Pituitary adenoma (adults) – mass
effect or apoplexy
o Craniopharyngioma (children) – mass
effect or apoplexy
o Sheehan syndrome – infarction after
pregnancy complicated w/ major blood
loss
 Poor lactation, loss of pubic hair
and fatigue
o Empty sella syndrome – congenital
defect
 Herniation of arachnoid and CSF
into sella compresses and
destroys pituitary gland
POSTERIOR PITUITARY GLAND
 Central diabetes insipidus
o ADH deficiency due to hypothalamic or
posterior pituitary pathology
o Polyuria, polydipsia, life-threatening
dehydration
o HyperNa+, low urine osmo
o Tx: desmopressin
 Nephrogenic diabetes insipidus
o Impaired renal response to ADH
o Mutations or lithium and
demeclocycline
o No response to desmopressin
 SIADH
o Excessive ADH secretion
o Most often due to ectopic production
(small cell CA of lung***)
o CNS trauma, pulm infection,
cyclophohsphamide
o HypoNa+ and low serum osm 
neuronal swelling and cerebral edema
 mental status change in and
seizures
o Tx: free water restriction or
demeclocycline
THYROID GLAND
 Thryoglossal duct cyst
o Cystic dilation of thryoglossal duct
remnant
o Anterior neck mass
 Lingual thyroid
o Persistence of thyroid tissue @ base of
the tongue
 Hyperthyroidism
o weight loss w/ ↑appetite
o heat intolerance, sweating
o tachycardia, ↑CO (↑β1-receptors)
o arrhythmia
o tremor, anxiety, insomnia, heightened
emotions
o starting gaze w/ lid lag
o diarrhea w/ malabsorption
o oligomenorrhea
o bone resorption w/ hyperCa2+
(osteoporosis)
o ↓muslce mass w/ weakness
o Hypocholesterolemia
o Hyperglycemia
 Graves disease
o IgG that stimulates TSH-receptor
 HLA-DR3
o Women of childbearing age
o Hyperthyroidism
o Diffuse goiter
o Exophthalmos and pretibial myxedema
(GAGs)
o Scalloping of colloid***
o Chronic inflammation
o ↑total and free T4, ↓TSH
o Thyroid storm: elevated CATs and
massive hormone excess (response to
stress)  arrhythmia, hyperthermia,
vomiting, hypovolemic shock
 Tx: PTU
 Multinodular goiter
o Enlarged thyroid w/ multiple nodules
o a/w iodine deficiency
o usually euthyroid
 Cretinism
o Hypothyroidism in neonates/infants
o MR, short stature, skeletal
abnormalities, coarse facies, enlarged
tongue, umbilical hernia
o Causes: maternal hypothyroidism,
thyroid agenesis, dyshormonogenetic
goiter (defect in thyroid peroxidase),
iodine deficiency
 Myxedema
o Hypothyroidism in adults
o ↓BMR and SNS activity
o GAGs  deepening of voice and large
tongue
o Weight gain
o Slowing of mental activity
o Muscle weakness
o Cold intolerance, ↓sweating
o Bradycardia, ↓CO  SOB and fatigue
o Oligomenorrhea
o Hypercholesterolemia
o Constipation
o Causes: iodine deficiency, lithium,
radioablation of thyroid
 Hashimoto thyroiditis
o HLA-D5***
o Antithyroglobulin and antimicrosomal
antibodies (sign of thyroid dmg)***
o Initial hyperthyroidism  progress to
↓T4 and ↑TSH
o Germinal centers and Hurthle cells
o ↑risk for B-cell lymphoma (marginal
zone)  enlarging thyroid
 Subacute granulomatous (De Quervain)
thyroiditis
o Granulomatous thyroiditis after viral
infection
o TENDER nodule w/ transient
hyperthyroidism
o Self-limited; does NOT progress to
hypothyroidism
 Reidel fibrosing thyroiditis
o Extensive fibrosis  rock hard thyroid
o Fibrosis may involve local structures
o Mimics anaplastic carcinoma (but pts
are younger and no malignant cells)
THYROID NEOPLASIA
 Follicular adenoma
o Benign prolif of follicles surrounded by
fibrous capsule
o Usually non-functional
 Papillary carcinoma
o MC type of thyroid CA (80%)
o Exposure to ionizing radiation in
childhood***
o Orphan Annie eyes***
o Psammoma bodies
o Spreads to cervical lymph nodes
o GOOD prognosis
 Follicular carcinoma
o Malignant prolif of follicles surrounded
by capsule w/ INVASION through
capsule
o Hematogenous metastases***
 Medullary carcinoma
o Malignant prolif of parafollicular C-
cells
o Chromogranin+
o Secrete calcitonin  deposits as
amyloid***
o HypoCa2+
o a/w mutates in RET oncogene***
 MEN 2A – medullary CA,
pheochromocytoma, parathyroid
adenoma
 MEN 3A – medullary CA,
pheochromocytoma,
ganglioneuromas of oral mucosa

Anaplastic carcinoma
o Undifferentiated malignant tumor
o Elderly
 o Invades local structures  dysphagia
or respiratory compromise
o POOR prognosis
PARATHYROID GLANDS
-PTH activates OSTEOBLAST to activate osteoclast
-increases vitD activation
-↑renal reabs of Ca2+, ↓reabs of PO4-
 Primary hyperparathyroidism
o Parathyroid adenoma (>80%)
 Benign neoplasm of ONE gland
 Mostly asymp hyperCa2+
 Nephrolithiasis, nephrocalcinosis
 CNS disturbance
 Constipation, PUD, acute
pancreatitis
 Osteitis fibrosa cystica
o ↑PTH
o ↑serum Ca2+, ↓serum PO4-***
o ↑urinary cAMP***
o ↑serum alkaline phosphatase
 Secondary hyperparathyroidism
o Excess PTH due to extrinsic causes: MC
chronic renal failure
o Renal insuff  ↓phosphate excretion
 free PO4- binds Ca2+  hypoCa2+
stimulates all 4 glands  ↑PTH
o ↑PTH
o ↓serum Ca2+, ↑serum PO4-***
o ↑serum alkaline phosphatase
 Hypoparathyroidism
o Low PTH
o Causes: autoimmune, surgical excision,
DiGeorge syndrome***
o HypoCa2+
 Numbness, tingling
 Muscle spasms – Trousseau sign
(tightening BP cuff) and Chvostek
sign (tapping on facial nerve)
o ↓PTH, ↓serum Ca2+
 Pseudohypoparathyroidism
o End-organ resistance to PTH
o AD (altered Gs), a/w short stature and
short 4th/5th digits
o ↑PTH, ↓serum Ca2+
ENDOCRINE PANCREAS
 Type I DM
o HLA-DR3 and HLA-DR4
o Inflammation and destruction of islets
by T-cells
o Weight loss, low muscle mass,
polyphagia
o Diabetic ketoacidosis 
hyperglycemia, AG metabolic acidosis,
hyperK+
o When give insulin  hypoK+
o Kussmaul respiration and fruity
halitosis
 Type 2 DM
o Insulin resistance  hyperinsulinemia
 beta cell exhaustion
o Amyloid deposition in islets
o Hyperosmolar non-ketotic coma 
very high blood glc >500
o Life-threatening diuresis w/
hypotension and coma
o No ketones b/c has insulin
 Long term consequences of DM
o Non-enzymatic glycosylation
 Cardiovascular dz
 Peripheral dz
 Glomerulosclerosis
 Kimmelstiel-Wilson dz
 HbA1c***
o Aldose reductase converts glc 
sorbitol***  cataracts, PN,
impotence, blindness
 Pancreatic endocine neoplasms
o MEN 1: pancreatic islet tumor,
parathyroid hyperplasia, pituitary
adenoma
o Insulinoma – episodic hypoglycemia
 ↓glc, ↑insulin, ↑C-peptide
o Gastrinomas – ZE syndrome 
multiple ulcers that may extend into
jejunum
o Somatostatinomas – achlorhydria
(inhibit gastrin) and cholelithiasis w/
steathorrea (inhibit CCK)
o VIPomas – watery diarrhea, hypoK+,
achlorhydria
ADRENAL CORTEX
 Cushing syndrome
o ↑cortisol
o Muscle weakness w/ thin extremities
(break down muscle for
gluconeogenesis)
o Moon facies, buffalo hump, truncal
obesity (↑insulin)
o Purple striae (thinning of skin)
o HTN
o Osteoporosis
o Immune suppression
o Causes:
 exogenous sources (bilateral
adrenal atrophy***)
 adrenal
adenoma/hyperplasia/carcinoma
(atrophy of uninvolved gland)
 ACTH-secretion pituitary
adenoma (bilateral hyperplasia)
 Paraneoplastic ACTH secretion
(small cell CA of lung, bilateral
hyperplasia)
o High-dose dexamethasone 
suppresses pituitary ACTH, but not
ectopic ACTH from small cell lung
CA***
 Conn syndrome
o ↑aldosterone
o HTN, hyperNa+, hypoK+
o Metabolic ALKALOSIS
o Primary  adrenal adenoma (high
aldo, low renin)
o Secondary  ↑RAAS
 Congenital adrenal hyperplasia
o 21-hydroxylase deficiency
 ↑ACTH
 ↓cortisol and aldosterone
 ↑androgens  clitoral
enlargement in females,
precocious puberty in males
 Adrenal insufficiency
o Waterhouse-Friderichsen syndrome
 Hemorrhagic necrosis of adrenal
glands due to DIC in children w/
N. meningitidis
 bilateral
o Addison dz (chronic insufficiency)
 Autoimmune, TB, metastatic
carcinoma from lung
 Primary  ↑ACTH levels 
hyperpigmentation
 Secondary  no
hyperpigmentation
ADRENAL MEDULLA
 Pheochromocytoma
o Brown, chromaffin+ tumor
o ↑urine metanephrines and
vanillylmandelic acid
o Tx: surgical excision and
phenoxybenzamine
o Rules of 10s: 10% bilateral, 10%
familial, 10% malignant, 10% located
outside adrenal medulla
o a/w MEN2A, 2B, VHL dz,
neurofibromatosis type 1
INFLAMMATORY BREAST CONDITIONS
 Acute mastitis
o Mostly S. aureus
o a/w breast-feeding  fissures
o erythematous breast w/ purulent
nipple discharge
o tx: continued feeding and abx
 Periductal mastitis
o Inflammation of subareolar ducts
o a/w smokers (vitA depletion) 
squamous metaplasia of lactiferous
ducts  blockage and inflammation
o subaerolar mass + nipple retraction***
 Mammary duct ectasia
o Dilation of subareolar ducts
o a/w multiparous postmenopausal
women
o green-brown nipple discharge
o chronic inflammation w/ plasma cells
 Fat necrosis
o a/w trauma
o saponification  calcifications on
mammography
o necrotic fat w/ giant cells

BENIGN BREAST TUMORS and FIBROCYSTIC
CHANGE
 Fibrocystic change
o MC change in premenopausal breasts
o Lumpy breasts**
o Cysts w/ blue-dome appearance***
o Benign
o But some changes a/w with ↑risk of
invasive carcinoma (for BOTH breasts):
 Fibrosis, cysts, apocrine
metaplasia*** – NO ↑risk
 Ductal hyperplasia and sclerosing
adenosis  2x ↑risk
 Atypical hyperplasia  5x ↑risk
 Intraductal papilloma
o Papillary growth into large duct
o Fibrovascular projections lined by
epithelial and myoepithelial cells
o Bloody nipple discharge in
premenopausal women***
o Distinguish from papillary carcinoma
which does NOT have myoepithelial
cells (older postmenopausal
women)***
 Fibroadenoma
o Tumor of fibrous tissue and glands
o Benign, no risk of CA
o Premenopausal females
o Well-circumscribed, mobile, marble-
like amss
o Es-sensitive
 Phyllodes tumor
o Looks like fibroadenoma
o Overgrowth of fibrous component 
leaf-like projections***
o Postmenopausal females
o Can be malignant
BREAST CANCER
 Ductal carcinoma in situ (DICS)
o No mass
o Calcifications
o Comedo type – central necrosis and
dystrophic calcification
o a/w Paget’s disease (extends to skin)
 suggests underlying carcinoma***
 Invasive ductal carcinoma (MC type)
o Duct-like structures in desmoplastic
stroma
o Forms mass
o Dimpling of skin or retraction of nipple
o Tubular CA – tubules, lack
myoepithelium (good prog)
o Mucinous CA –tumor cells floating in
mucin (good prog, elderly)
o Medullary CA – large, high-grade cells
w/ lymphocytes and plasma cells
 a/w BRCA1 carriers***
 relatively good prognosis
 Inflammatory CA – carcinoma in dermal
lymphatics
o Inflamed, swollen breast (looks like
acute mastitis)
o POOR prognosis
 Lobular carcinoma in situ (LICS)
o Detected incidentally
o No mass, no calcifications
o Dyscohesive cells  lacking E-
cadherin***
o Often multifocal and bilateral
o LOW risk of progression to invasive
o Tx: tamoxifen
 Invasive lobular carcinoma
o Grows in single file***
o No ducts b/c lack E-cadherin
 Prognostic and predictive factors
o Metastasis is most important
o Sentinel node biopsy to assess axillary
lymph nodes
 Hereditary breast cancer
o 10% of breast cancers
o Multiple 1st degree relatives, tumor at
early age, multiple tumors in single pt
o BRCA1  breast and ovarian CA
o BRCA2  breast CA in males
 Male breast cancer
o Subareolar mass in older males
 High density breast tissue
o MC ductal
o a/w BRCA2 and Klinefelter syndrome*
CNS DEVELOPMENT ABNORMALITIES
 Neural tube defects
o Low folate PRIOR to conception***
o ↑AFP in amniotic fluid and maternal
blood***
o Anencephaly – absence of skull and
brain
 Frog-like appearance
 Maternal polyhydramnios
o Spina bifida
 Dimple or patch of hair overlying
vertebral defect
o Meningocele – protrusion of meninges
o Meningomyelocele – protrusion of
meninges + spinal cord
 Cerebral aqueduct stenosis
o MCC of hydrocephalus in newborns
(non-communicating)
o Enlarging head circumference
 Dandy-Walker malformation
o Failure of cerebellar vermis to develop
o Massively dilated 4th ventricle
(posterior fossa) w/ absence
cerebellum
o Accompanied by hydrocephalus
 Arnold-Chiari malformation
o Congenital extension of cerebellar
tonsils through foramen magnum
o Obstruction to CSF  hydrocephalus
o a/w meningomyelocele and
syringomyelia***
SPINAL CORD LESIONS
 Syringomyelia
o Cystic degeneration of spinal cord
o a/w trauma or Arnold-Chiari
o usually occurs at C8-T1***
o sensory loss of pain/temp w/ sparing
of fine touch and position sense in
UPPER extremities  cape-like dist
o involves anterior white commissure
o Syrinx expansion can involve other
spinal tracts
 Muscle atrophy and weakness
(anterior horn)
 Horner syndrome – ptosis,
miosis, anhidrosis (lateral horn of
hypothalamic tract)
 Poliomyelitis
o Damage to anterior motor horn due to
poliovirus
o LMN signs: flaccid paralysis, muscle
atrophy, fasciculations, weakness,
decreased tone, impaired reflexes,
negative Babinski
 Werdnig-Hoffman disease
o Inherited degeneration of anterior
motor horn (AR)
o “floppy baby”  death within few
years after birth
 Amyotrophic lateral sclerosis (ALS)
o Degenerative d/o of UMNs and
LMNs*** of corticospinal tract
 LMN signs (anterior motor horn)
 UMN signs (lateral corticospinal
tract degen): spastic paralysis,
hyperreflexia, increased muscle
tone, positive Babinski sign (toe
up)
o Early sign = atrophy of hands
o NO sensory impairment***
o Middle-aged adults
o a/w zinc-copper superoxide
dismutase*** mutation (SOD1) in
some familial cases
 Friedreich ataxia
o Degeneration of multiple spinal cord
tracts  loss of proprio/vibration,
muscle weakness in lower extremities,
loss of DTRs
o AR, expansion of GAA in frataxin
gene***
  Essential for mitochondrial iron
regulation  iron buildup  free
radical damage
o Presents in early childhood,
wheelchair-bound within few years
o a/w hypertrophic cardiomyopathy
MENINGITIS
 inflammation of leptomeninges = pia and
arachnoid
 GBS – neonates <1 mo
 Strep pneumo – everyone > 1mo
 N. meningitis – children and teens
(epidemic)
 H. influenza – non-vaccinated children
 Coxsackie – fecal-oral
 Fungal – immunocompromised pts
 Classic triad = headache, nuchal rigidity,
fever
 Can also have photophobia (viral), vomiting
and altered mental stasus
 Dx via lumbar puncture into subarachnoid
space
 Bacterial  PMNs, ↓glc
 Viral  lymphs, normal glc
 Fungal  lymphs, ↓glc
 Complications mostly with bacterial
o Death – herniation due to cerebral
edema
o Hydrocephalus, hearing loss, seizures –
sequelae to fibrosis
CEREBROVASCULAR DISEASE
 Global cerebral ischemia
o Etiologies
 Low perfusion (atherosclerosis)
 Acute ↓BF (cardiogenic shock)
 Chronic hypoxia (anemia)
 Repeated episodes of
hypoglycemia (insulinoma)
o If mild  transient confusion w/
prompt recovery***
o If severe  diffuse necrosis 
vegetative state
o If moderate  Watershed areas***
most sensitive (ACA and MCA junction)
 Pyramidal neurons of cerebral
cortex (layers 3, 5, 6)  laminar
necrosis
 Pyramidal neurons of
hippocampus (temporal lobe) 
long-term memory
 Purkinje layer of cerebellum 
integrates sensory perception w/
motor control
 Ischemic stroke
o Regional ischemia  focal neurologic
deficits for > 24 hrs
o If < 24 hrs = TIA
o Thrombotic – rupture of
atherosclerotic plaque
 Pale infarct in periphery of cortex
o Embolic – most involves MCA
 Hemorrhagic infarct in periphery
(emboli can be lysed)
o Lacunar stroke – hyaline
arteriolosclerosis
 Most involve lenticulostriate
vessels  small cystic areas of
necrosis
 Internal capsule  pure motor
stroke
 Thalamus  pure sensory stroke
o Liquefactive necrosis
 Red neurons*** = early finding
(12 hrs after infarction)
o Coagulative necrosis (24 hrs)
o Infiltration by PMNs (1-3 days)
o Microglial cells (4-7 days)
o Fluid filled cystic space surrounded by
gliosis (reactive astrocytes)
 Intracerebral hemorrhage
o Bleed into parenchyma
o Rupture of Charcot-Bouchard
microaneurysms*** of lenticulostriate
vessels
o a/w HTN (hyaline weakens vessel)
o most commonly affects basal
ganglia***
o severe headache, N/V, coma
 Subarachnoid hemorrhage
o Bleed into SAS
o Rupture of berry aneurysms (lack
media layer)***
o a/w Marfan syndrome and ADPKD
o most commonly affects anterior circle
of Willis @ br pts of anterior
communicating artery***
o “worst headache of life” + nuchal
rigidity
o Xanthochroma*** (yellow CSF due to
bilirubin breakdown)
CNS TRAUMA
 Epidural hemorrhage
o Blood btw dura and skull
o Fracture of temporal bone*** 
rupture of middle meningeal artery***
o Wedge-shaped
o Lucid interval may precede neurologic
signs
o Herniation = lethal complication
 Subdural hemorrhage
o Blood under dura – covers entire brain
o Tearing of bridging veins***
o Crescent-shaped
o Progressive neurological signs
o ↑rate in elderly (cerebral atrophy)
o Herniation = lethal complication
 Herniation
o 1. Uncal herniation
 Compress CN III  eyes down
and out, dilated
 Compress PCA  occipital lobe
infarct  contralateral
homonymous hemianopsia
 Rupture of paramedian artery 
Duret (brainstem) hemorrhage
o 3. Subfalcine herniation
 Compress ACA  infarction
o 6. Tonsillar herniation
 Compress brain stem 
cardiopulmonary arrest
DEMYELINATING DISORDERS
Leukodystrophies
 Metachromatic leukodystrophy – deficiency
of arylsulfatase (MC)
o Myelin cannot be degraded 
accumulates in lysosomes of
oligodendrocytes
 Krabbe disease – deficiency of
galactocerebroside β galactosidase
o Galactocerebroside accumulates in
macrophages
 Adrenoleukodystrophy – impaired addition
of coenzyme A to long-chain fatty acides
o X-linked
o Accumulation of FAs damages adrenal
glands and WM of brain
 Multiple sclerosis
o Autoimmune destruction of CAN
myelin + oligodendrocytes
o MC in young adults (F > M)
o HLA-DR2
o Relapsing neurologic deficits w/
periods of remission
 Blurred vision, vertigo, scanning
speech, internuclear
ophthalmoplegia, hemiparesis,
unilateral sensation loss, lower
extremity weakness/loss of
sensation, bowel, bladder, sexual
dysfunc
o Dx by MRI and lumbar puncture
 Mutifocal plaques (gray)
 Oligoclonal IgG, myelin basic
protein
 Subacute sclerosing panencephalitis
o Progressive, debilitating encephalitis
 death
o a/w measles virus*** infection in
infancy, neurologic signs yrs later
o viral inclusions within neurons (GM)
and oligodendrocytes (WM)
 Progressive multifocal leukoencephalopathy
o JC virus infection of oligodendrocytes
o Immunosuppression  reactivation of
latent virus
o Rapidly progressive neurologic signs
leading to death
 Central pontine myelinolysis
o Focal demyelination of pons (anterior
brainstem)
o Rapid IV correction of hypoNa+***
o Presents w/ classic bilateral paralysis
o “locked-in” syndrome
DEMENTIA and DEGENERATIVE DISORDERS
 Alzheimer disease
o Degenerative dz of cortex  MCC of
dementia
o Slow-onset memory loss (begins with
short, progresses to long)
o Progressive disorientation
o Loss of learned motor/language skill
o Changes in behavior and personality
o Pts become mute and bedridden
o Focal neurologic dz NOT seen in early
dz
o Risk increases w/ age
 ε4 allele of ApoE  ↑risk
 ε2 allele of ApoE  ↓risk
o Early onset a/w:
 Presenilin 1 and 2 mutations
 Down syndrome
o Cerebral atrophy
o Neuritic plaques (Aβ amyloid, from
APP, chromo21)
o Neurofibrillary tangles
(hyperphosphorylated tau protein)
o Loss of cholinergic neurons in nucleus
basalis of Meynert
 Vascular dementia
o Multifocal infarction due to HTN,
atherosclerosis or vasculitis
o 2nd MCC of dementia
 Pick disease
o Degen of frontal and temporal cortex
o Pick bodies = round aggregates of tau
protein
o Behavioral and language symps early
o Dementia later
 Parkinson disease
o Degenerative loss of dopaminergic
neurons in substantia nigra of basal
ganglia
o Some a/w MPTP exposure
o Tremor, Rigidity,
Akinesia/bradykinesia, Postural
instability/shuffling gait
o α-synuclein (Lewy bodes)
o dementia late in dz
 Lewy body dementia
o Early onset dementia
o Hallucinations + parkinsonism
 Huntington disease
o Degen of GABA neurons in caudate
nucleus of basal ganglia
o AD, chromo4, CAG expansion
 Expansion in spermatocyte***
o Chorea (onset around age 40)
o Progress to dementia
 Normal pressure hydrocephalus
o ↑CSF results in dilated ventricles
(stretch corona radiate)
o Can cause dementia in adults
o Classic triad = urinary incontinence,
gait instability, dementia
o “wet, wobbly, wacky”
o Lumbar puncture improves symps
o Tx: ventriculoperitoneal shunt
 Spongiform encephalopathy
o PrPc (α-helix) converted into PrPsc (β-
pleated, not degradable)
o Intracellular vacuoles (spongy degen)
o Creutz-Jakob disease
 Sporadic, exposure to GH or
corneal transplant
 Rapidly progressive dementia
a/w ataxia
 Startle monoclonus – involuntary
contraction w/ minimal stimuli
 Spike-wave complexes
 Death <1 yr
o Variant CJD – related to exposure to
bovine spongiform encephalopathy
o Familial fatal insomnia – inherited
 Severe insomnia + exaggerated
startle response
CNS TUMORS
 Metastatic (50%)
o Multiple, well-circumscribed lesions in
gray-white junction
o Mostly from lung, breast, kidney
 Glioblastoma multiforme
o Malignant, high-grade of astrocytes
o MC 1⁰ malignant CNS tumor in adults
o Cerebral hemisphere  crosses corpus
callosum  butterfly lesion
o Pseudopalaisading, endo prolif
o GFAP+***
 Meningioma
o Benign tumor of arachnoid cells
o Adults (F > M)
o Seizures
o Tumor compresses, but does not
invade
o Round mass attached to dura
o Whorled pattern, psammoma bodies
 Schwannoma
o Benign tumor of Schwann cells
o MC involves CN VIII @
cerebellopontine angle  loss of
hearing and tinnitus
o S100+***
o Bilateral seen in neurofibromatosis
type 2***
 Oligodendroglioma
o Malignant tumor of oligodendrocytes
o Calcified tumor in WM***
o Often involves frontal lobe
o Seizures
o “fried-egg” appearance
*most common CNS tumors in childhood,
infratentorial
 Pilocytic astrocytoma*
o Benign tumor of astrocytes
o MC CNS tumor in children
o Arises in cerebellum
o Cystic lesion w/ mural nodule
o Rosenthal fibers*** – thick
eosinophilic processes of astrocytes
o GFAP+***
 Medulloblastoma*
o Malignant tumor from granular cells of
cerebellum (neuroectoderm)
o Small, round blue cells
o Homer-Wright rosettes*
o Spreads to CSF  poor prognosis
 “Drop metastasis” involves cauda
equina
 Ependymoma*
o Malignant tumor of ependymal cells
o MC arises from 4th ventricle  may
cause hydrocephalus
o Perivascular pseudorosettes***
 Craniopharyngioma
o Tumor arises from epithelial remnants
of Rathke’s pouch (posterior pituitary)
o Supratentorial mass in children or
young adults
o Compress optic chiasm  bilateral
hemianopsia
o Calcifications common
o Benign, but recurs
SKELETAL SYSTEM
 Achondroplasia
o Activating mutation of FGFR3*** 
inhibits growth  poor endochondral
bone formation
o sporadic and related to advanced
paternal age
o short extremities
o normal head and chest
o mental function, life span, fertility not
affected
 Osteogenesis imperfecta
o Defect of bone resorption  weak
bone
o AD defect in collagen I synthesis
o Multiple fractures
o Blue sclera (choroidal vein exposure)
o Hearing loss (bones of middle ear
fracture easily)
 Osteopetrosis
o Defect of bone resorption  thick,
heavy bone that fractures easily
o Poor osteoclast function
 Carbonic anhydrase II mutation
 o Bone fractures
o Pancytopenia (bony replacement of
marrow)
o Vision and hearing impairment
(impingement of cranial nerves)
o Hydrocephalus (narrowing of foramen
magnum)
o Renal tubular acidosis
o Tx: BM transplant
 Rickets/osteomalacia
o Defective mineralization of osteoid
o Low levels of vitamin D  low Ca2+
and PO4-
o Children  abnormal bone
mineralization
 Pigeon-breast deformity
 Frontal bossing
 Rachitic rosary (costochondral
junction)
 Bowing of legs
o Adults  weak bones, easily fracture
 Esp hips (weight bearing)
o ↓serum Ca2+, ↓PO4-
o ↑PTH, ↑alkaline phosphatase
 Osteoporosis
o Reduction in trabecular bone mass 
porous bone, easily fracture
o Bone mass lost more quickly w/ lack of
weight-bearing exercise, poor diet,
decreased Es (menopause)
o Most common forms = senile and
menopausal
o Bone pain and fractures in weight-
bearing areas  vertebrae (loss of
height and kyphosis), hip, distal radius
o All serum levels are normal
o Bisphosphonates – induce apoptosis of
osteoclasts
o CONTRA: glucocorticoids
 Paget disease of bone
o >60 yrs
o Imbalance btw osteoclast and
osteoblast function
o Localized process***
o 3 distinct stages:
 Osteoclastic
 Mixed
 Osteoblastic
o Result  thick, sclerotic bone that
fractures easily
o Mosaic pattern of lamellar bone***
o Bone pain, microfactures
o Increased hat size (skull affected)
o Hearing loss (impingment of nerve)
o Lion-like facies***
o Isolated ↑serum alkaline phosphatase
o Calcitonin and bisphosphonates
↓osteoclast activity
o High-output cardiac failure (formation
of AV shunts in bones)
o ↑risk of osteosarcoma
 Ostepmyelitis
o Infection of marrow and bone
o Hematogenous spread of bacteria
o Children  seeds metaphysis
o Adults  seeds epiphysis
o S. aureus = MCC
o TB  Pott disease
o Bone pain w/ systemic signs of
infection
 Avascular (aseptic) necrosis
o Ischemic necrosis
o Trauma or fracture MC
o Steroids, sickle cell and caisson dz (N2
gas emboli)
o Osteoarthritis and fracture
BONE TUMORS
 Osteoma
o Benign tumor of bone
o Facial bones
o a/w Gardner syndrome
 Osteoid osteoma
o Benign tumor of osteoblasts
o Young adults <25yrs
o Arises in cortex of long bones
o Pain resolves w/ ASA
o Bnoy mass w/ radiolucent core
(osteoid)
 Osteoblastoma
o >2 cm
o Arises in vertebrae
o Bone pain does NOT resolve w/ ASA
 Osteochondroma
o Tumor of bone w/ overlying cartilage
cap**
o MC benign tumor of bone
o Arises from lateral projection of
metaphysis
o Bone continuous w/ marrow space
o Rarely transform to chondrosarcoma
 Osteosarcoma
o Malignant prolif of osteoblasts 
pleomorphic, osteoid-producing
o Peek in teens (familial retinoblastoma,
Paget dz, radiation exposure)
o Arise in metaphysis of long bones
(distal femur or proximal tibia 
around knee)
o Bone pain w/ swelling
o Sunburst appearance***
o Lifting of periosteum (Codman
triangle)
 Giant cell tumor
o Multinucleated giant cells and stromal
cells
o Younger adults
o Arises in epiphysis*** of long bones
(region of knee)
o Soap-bubble appearance***
 Ewing sarcoma
o Malignant prolif of poorly-
differentiated cells from
neuroectoderm
o Small, round blue cells
o t(11;22)**
o Onion skin***
o Responsive to chemotherapy
 Chondroma
o Benign tumor of cartilage
o Medulla of small bones of hands/feet*
o Radiolucent spot in middle of bone
 Chondrosarcoma
o Malignant cartilage-forming tumor
o Medulla of pelvis or central skeleton*
 Metastatic tumors
o More common than primary
o Osteolytic (punched-out lesions)
o Prostatic CA
JOINT
 Osteoarthritis
o Degenerative joint dz
o a/w obesity and trauma
o DIPs, PIPs, hips, lower lumbar spine,
knee
o Joint stiffness that worsens during the
day
o Disruption of cartilage floating in joint
space “joint mice”
o Eburnation of subchondral bone (bone
on bone)
o Osteophyte formation
 DIP  Heberden nodes
 PIP  Bouchard nodes
 Rheumatoid arthritis
o Systemic, a/w HLA-DR4***
o Synovitis leading to formation of
pannus (inflamed granulation tissue)
o Destruction of cartilage + ankylosis
(fusion) of joints
o Arthritis w/ morning stiffness that
improves w/ activity
o SYMMETRIC involvement
o PIP  swan-neck deformity
o Wrist  ulnar deviation
o Elbows, ankles, knees
o DIPs are SPARED***
o Joint-space narrowing, loss of
cartilage, osteopenia
o Fever, malaise, weight loss, myalgias
 o Rheumatoid nodules – central zone of
necrosis surrounded by epitheloid
histiocytes
o Vasculitis
o Baker cyst*** – swelling of bursa
behind the knee
o Pleural effusion, lymphadenopathy,
interstitial lung fibrosis
o IgM autoantibody against Fc portion of
IgG***
o Complications: anemia of chronic dz
and secondary amyloidosis (SAA AA)
 Seronegative spondyloarthropathies
o Lack of RF
o Axial skeletal involvement
o HLA-B27***
o Ankylosing spondyloarthritis –
sacroiliac joints and spine
 Young males
 Lower back pain
 Fusion of vertebrae  bamboo
spine
 Uveitis, aortitis
o Reiter syndrome
 Classic triad = arthritis, urethritis,
conjunctivitis
 Young adults weeks after GI or
chlamydia infection
o Psoriatic arthritis – axial and peripheral
joints
 DIPs  sausage fingers and toes
 Infectious arteritis
o N gonorrhoeae – young adults
o S aureus – children and adults
o Affects SINGLE joint (usually knee)
 Gout
o Monosodium urate crystals in joints
o From purine metabolism
o Secondary forms:
 Leukemia and myeloproliferative
d/o  high cell turnover
 Lesch-Nyhan syndrome
 Renal insufficiency
o Painful arthritis of BIG TOE (podagra)
o A/w alcohol and meat
o Chronically  tophi (white, chalky
aggregates of uric acid w/ fibrosis and
giant cells)
o Needle-shaped crystals w/ negative
birefringence***
 Pseudogout
o Deposition of calcium pyrophosphate
dehydrate (CPPD)
o Rhomboid-shaped crystals w/ positive
birefringence***
SKELETAL MUSCLE
-all have ↑CK
 Dermatomyositis
o Inflammation of skin and skeletal
muscle
o a/w gastric CA
o Bilateral, PROXIMAL muscle weakness
(can’t comb hair or climb stairs)
o Rash of upper eyelids, malar rash
o Red papules on elbows, knuckles and
knees (Grotton lesion)
o Positive ANA and anti-Jo-1 antibody**
o CD4+ T-cell perimysial inflammation w/
perifascicular atrophy
 Polymyositis
o Inflammation of skeletal muscle
o Endomysial CD8+ T-cell
inflammation***
 X-linked muscular dystrophy
o Replacement of skeletal muscle w/
adipose tissue
o Duchenne muscular dystrophy –
deletion of dystrophin
 Proximal muscle weakness at 1 yr
 Calf pseudohypertrophy
 Death from cardiac or respiratory
failure
o Becker muscular dystrophy – mutated
dystrophin
 Milder case
NEUROMUSCULAR JUNCTION
 Myasthenia gravis
o Autoantibodies against postsynaptic
ACh receptor
o Muscle weakness w/ use, improves
with rest
o Ptosis and diplopia
o Tx: AChE inhibitors
o a/w thymic hyperplasia or thymoma 
thymectomy may help
 Lambert-Eaton syndrome
o Antibodies against presynaptic calcium
channels  impaired ACh release
o a/w small cell CA
o PROXIMAL muscle weakness that
IMPROVES w/ use***
o Eyes spared
SOFT TISSUE TUMORS
 Lipoma
o Benign tumor of adipose tissue
o MC benign soft tissue tumor in adults
 Liposarcoma
o Malignant adipose tissue tumor
o Lipblast = characteristic cell
 Rhabdomyoma
o Benign tumor of skeletal muscle
o Cardiac rhabdomyoma a/w tuberous
sclerosis***
 Rhabdomyosarcoma
o Malignant tumor of skeletal muscle
o MC malignant soft tissue tumor in
children
o Desmin+
o MC head and neck
o Vagina = classic in young girls
INFLAMMATORY DERMATOSES
 Atopic (eczematous) dermatitis
o Type I HSR
o Pruritic, erythematous, oozing rash on
face and flexor surfaces
o a/w asthma and allergic rhinitis
 Contact dermatitis
o Pruritic, erythematous, oozing rash w/
vesicles and edema
o Type IV HSR*** (poison ivy, nickel
jewelry)
 Acne vulgaris
o Comedones, pustules, nodules
o Androgen-associated sebum
production
o P acnes form lipases
 Psoriasis
o Well-circumscribed, salmon-colored
plaques w/ silvery scale
o Extensor surfaces and scalp
o Pitting of nails
o Excessive keratinocyte prolif
o Autoimmune a/w HLA-C
o acanthosis, parakeratosis, Munro
microabscesses (PMNs), thinning of
epidermis above elongated dermal
papillae (Auspitz sign  easy bleeding
when picked off)
 Lichen planus
o Pruritic, Planar, Polygonal, Purple
Papules
o Wickham striae (white lines)
o Involves wrists, elbows and oral
mucosa
o Dermal-epidermal junction
inflammation  “saw-tooth”
appearance***
o a/w chronic hepC
BLISTERING DERMATOSES
 Pemphigus vulgaris
o Autoimmune destruction of
desmosomes btw keratinocytes
o IgG against desmoglein***
 Fish net pattern***
o Type II HSR
o Thin-walled  easily rupture (Nikolsky
sign)
o Affects skin and oral mucosa
 Bullous pemphigoid
o Autoimmune destruction of
hemidesmosomes btw basal cells and
BM
o IgG against BM collagen***
o Linear pattern***
 o Tense bullae
o Skin only (mucosa spared)
 Dermatitis herpetiformis
o IgA deposition at tips of dermal
papillae
o a/w celiac dz
 Erythema multiforme
o Targetoid rash and bullae
o a/w HSV infection
o if involve oral mucosa and lip 
Stevens-Johnson syndrome
 severe form = toxic epidermal
necrolysis  diffuse sloughing of
skin
INFECTIOUS DISORDERS
 Impetigo
o S aureus or S pyogenes
o Children w/ honey-colored serum
 Cellulitis
o S aureus or S pyogenes
o Dermal or sub Q
o Red, tender, swollen rash w/ fever
o Can progress to necrotizing fasciitis
o Gas gangrene  C perfringens
o Surgical emergency
 Staphylococcal scalded skin syndrome
o Exfoliative A and B toxins 
epidermolysis of stratum granulosum
o Significant skin loss
 Verruca (wart)
o Flesh-colored papules
o a/w HPV infection
o hands and feet most common
 Molluscum contagiosum
o Firm, pink, umbilicated papules
o a/w poxvirus  cytoplasmic inclusions
o most often in children
o also in sexually active adults and
immunocompromised pts
EPITHELIAL TUMORS
 Seborrheic keratosis
o Benign, common in elderly
o “stuck-on”, coin-like, waxy
o Keratin pseudocysts**
o Leser-Trelat sign  sudden eruption
 GI carcinoma
 Acanthosis nigricans
o Epidermal hyperplasia  velvet-skin
o Axilla or groin
o a/w insulin resistance or malignancy
 Basal cell carcinoma
o MC cutaneous malignancy
o Risk factors: UVB, albinism, xeroderma
pigmentosum
o Central, ulcerated crater surrounded
by telangiectasia
o “pink, pearl-like papule”***
o Peripheral palisading***
o Metastasis is RARE
 SCC
o Keratin pearls
o Risk factors save as basal cell
o Addition risk factors:
immunosuppression***, arsenic,
chronic inflammation
o Ulcerated, nodular mass
o Classically on lower lip***
o Actinic keratosis = precursor
o Keratoacanthoma = well-differentiated
SCC that develops rapidly and
regresses spontaneously
 Cup-shaped tumor filled w/
keratin debris
DISORDERS OF PIGMENTATION and
MELANOCYTES
 Vitiligo – localized hypopigmentation  Acral lentiginous
o Autoimmune destruction of  Starts deep, poor prog
melanocytes  Palms or soles
 Not related to UV exposure
 Albinism - congenital lack of pigmentation
o Tyrosinase deficiency
o ↑risk of SCC, basal cell CA, melanoma
due to reduced UVB protection
 Freckle (ephelis)
o Small, tan/brown macule
o Darkens w/ sun exposure
o ↑NUMBER of melanosomes***
 Melasma
o Mask-like hyperpigmentation of
cheeks
o a/w pregnancy and OTCs
 Nevus (mole)
o Benign prolif of melanocytes
o Congenital nevus  a/w hair
o Acquired nevi:
 Starts at dermal-epidermal
junction (common in children)
 Grows by extension into dermis
(compound)
 Junctional component is lose 
intradermal nevus (common in
adults)
o Dysplastic nevus = precursor to
melanoma
 Melanoma
o MCC death from skin cancer
o Risk factors like basal cell + dysplastic
nevus syndrome
o Variants:
 Superficial spread
 Most common, radial
growth, good prog
 Lengito maligna melanoma
 Lentiginous prolif (radial
growth), good prog
 Nodular
 Early vertical, poor prog