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Ch. 1 – Cell Injury and Responses

Reduced ox. phos. and depletion of ATP Reversible Injury
Damage to membrane → lysozomal enzymes into cytoplasm → leaks out Necrosis
Damage to DNA or proteins beyond repaire → suicide Apoptosis
Cell death that's always pathologic Necrosis
Plasma membrane/nuclear alterations, mitochondrial changes, dilation of ER Reversible Injury
Inc. eosinophilia; myelin figures; karyolysis; karyorrhexis Necrosis
Vessel obstruction → ischemia → infarct = this (not in brain) Coagulative Necrosis
Characterized by digestion of dead cells Coagulative Necrosis
Tissue turns into liquid viscous mass; CNS only has this Liquefactive Necrosis
Seen in local bacterial and sometimes fungal infections Liquefactive Necrosis
Coagulative necrosis in multiple tissue planes (i.e. extremities) Gangrenous Necrosis
Gangrenous necrosis + bacterial infection in it → liquefactive necrosis Wet Gangrene
Seen usually in Tb infection; granulomas Caseous Necrosis
Lipase from pancreas leaks out (acute pancreatitis) Fat Necrosis
Seen in immune rxns involving blood vessels; bright pink on H&E stain Fibrinous Necrosis
Necrotic debris not cleared out in time → calcium salts attracted Dystrophic Calcification
High-conductance channel after mitochondrial damage Mitochondrial Permeability Transition Pore
How peroxisomes decompose oxygen radicals Catalase
How mitochondria and cytosol decompose oxygen radicals Superoxide Dismutase (SOD)
Phospholipid dec, Phospholipase, Cytoskeletal damage (from Ca) Causes of Membrane Damage
Mitochondrial, Lysosomal, Plasma Membranes Damaged
From mitochondria; initiates apoptosis through caspase action Cytochrome C
Cell shrinkage, chromatin condensation, apoptotis bodies and blebs Morphology of apoptosis
Examples = caspase-8, caspase-9, and caspase-10 Initiator caspases
Examples = caspase-3 and caspase-6 Executioner caspases
Staining used to ID apoptotic cells Annexin V
Pro-apoptotic proteins stimulate cytocrhome C Intrinsic (Mitochondrial) Pathway
Two main anti-apoptotic molecules; seen in cancers Bcl-2 and Bcl-x
Normal function is to block activation of caspases; neutralized in apoptosis IAPs
TNF receptor family; TNFR1 and Fas (CD95) Extrinsic (Death Receptor-Initiated) Pathway
Part of inner side of membrane, flipped out in apoptotic cells → macrophages Phosphatidylserine
Complement protein that binds apoptotic bodies C1q
Checks DNA at G phase for damage; can start apoptosis if DNA is damaged p53
CTL methods of causing apoptosis Granzymes and Fas ligands
Seen in fat accumulation in heart muscle Tigered Effect
Accumulation of cholesterol in macrophages → foamy cells in connective tiss Xanthomas
Plasma cell ER becomes huge, produces these eosinophilic inclusions Russel Bodies
Pigment that clues you into free radical injury and lipid peroxidation Lipofuscin
Only brown-black endogenous pigment Melanin
Yellow to brown pigment that stores forms of iron Hemosiderin
Necrotic seeds surrounded by mineral (calcium) salts Psammoma Bodies

Ch. 2 – Inflammation
PGI2 (Prostacyclin), PGE1, PGE2, PGD2 Vasodilation
TxA2, LTC4, LTD4, LTE4 Vasoconstriction
LTC4, LTD4, LTE4 Inc Vascular Permeability
LTB4, HETE Chemotaxis, leukocyte adhesion
Pathway that produces leukotrienes and HETE 5-Lipoxygenase
Pathway that produces lipoxins 12-Lipoxygenase
Pathway that produces prostaglandins and thromboxane A2 Cyclooxygenase
Cytokines in acute inflammation TNF, IL-1, IL-6, Chemokines
Cytokines in chronic inflammation IL-12, IFN-y, IL-17
Starts 4 systems involved in inflammation (kinin, clotting, fibrinolytic, comp) Activated Hageman Factor (factor XIIa)
King cell of chronic inflammation Monocytes
Cleavage of this is the critical step in complement activation (all pathways) C3
Triggered by C1 binding to antibody-antigen complex Classical Complement Pathway
Triggered by endotoxin, cobra venom, etc.; NO antibodies Alternative Complement Pathway
Plasma mannose-binding lectin binds to carbs on microbes to activate C1 Lectin Pathway
Acts as an opsonin to promote phagocytosis C3b
Made up of multiple C9's and causes lysis of microbe MAC (membrane attack complex)
Stimulate histamine release to cause inflammation; anaphylatoxins C3a and C5a
Powerful chemotactic agent; activates lipoxygenase pathway → AA's C5a
Activation of this starts it all: clotting; histamine release; pain; fever Factor XII (Hageman factor)
Thrombin binds to this and triggers inflammation PAR-1
Causes PAIN during inflammation Bradykinin
Activator of Hagemen factor that allows for autocatalytic amplification Kallikrein
Blisters filled with clear fluid; no proteins; minor inflammation Serous Inflammation
Exudative inflammation; many proteins; fibrinoid exudate if real bad Fibrinous Inflammation
Seen in inflammation of meninges, pericardium, and pleura Fibrinous Inflammation
Lots of pus, neutrophls, liquefactive necrosis, edema fluid Suppurative/Purulent Inflammation
Seen in appendicitis or from pyogenic bacteria Suppurative/Purulent Inflammation
Local defect, surface of organ/tissue, sloughing of inflamed necrotic tissue Ulcers
Seen in mucosa of mouth/stomach/intestines/GU or skin in elderly Ulcers
Hallmark cell in acute inflammation Neutrophils
Hallmark cell in chronic inflammation Macrophages
Connective tissue replacement of damaged tissue; angiogenesis; fibrosis Morphology of chronic inflammation

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Lymphocytes, plasma cells, eosinophils, mast cells also seen Other cells in chronic inflammation
Aggregation of macrophages → epithelium-like; surrounded by lymphocytes Granuloma
Fusion of epithelioid cells Giant cells
Fever, acute-phase proteins, Leukocytosis, inc pulse/BP; chills Systemic effects of inflammation

Ch. 4 – Hemodynamic Disorders, Thrombosis, Shock

Edema that leaves a fingerprint Pitting Edema
Edema caused by this can affect all parts of the body Renal dysfunction
Engorged alveolar capillaries; alveolar septal edema Acute Pulmonary Congestion
Thickened and fibrotic septa; hemosiderin-laden macrophages (heart failure cells) Chronic Pulmonary Congestion
Central vein and sinusoids distended Acute Hepatic Congestion
Centrilobular regions are grossly red-brown and depressed; Chronic Passive Hepatic Congestion
Nutmeg liver Chronic Passive Hepatic Congestion
Causes = inc intravascular pressure, thrombocytopenia, uremia Petechiae
Causes = same as petechiae + trauma, vasculitis, amyloidosis Purpura
Bruises; larger than purpura Ecchymoses
AKA factor III or thromboplastin Tissue Factor
Starts off coagulation cascade in endothelial injury Tissue Factor
Prostacyclin, Nitric Oxide, Adenosine diphosphatase Antiplatelet Effects
Heparin, Thrombomodulin, Protein C, Protein S, TFPI Anticoagulant Effects
t-PA Fibrinolytic Effects
Exposed ECM, vWF Platelet Effects
TNF, IL-1, LPS, Tissue Factor Procoagulant Effects
PAI's Antifibrinolytic Effects
GpIIb-IIIa complex deficiency Glanzmann Thrombasthenia
GpIb deficiency Bernard-Soulier Syndrome
Factors in Intrinsic Pathway 12, 11, 9, 8
Factors in Extrinsic Pathway 7,
Factors in Common Pathway 10, 5, 2, 1, 13
Can occur following unfractionated heparin; Ab's to platelets Heparin-induced Thrombocytopenia
Lines of Zahn Thrombus
Thrombi in heart chambers or aortic lumen Mural thrombi
“Red” or “Stasis” thrombi Venous thrombi
Gelatinous w/ dark red dependent portion and a yellow “chicken fat” upper portion Postmortem thrombi
Sterile endocarditis with SLE Libman-Sacks endocarditis
Occur in venous occlusions, loose tissues, dual circ. tissues, everywhere Red Infarcts
Occur in end-arterial circulation (heart, spleen, kidney); dense tissue White Infarcts
Splenic infarcts are converted to this Abscess

Ch. 6 Normal Immune Response

Gene for TCR diversity RAG-1, RAG-2
Signal 1 of TCR complex CD3 and zeta proteins
Signal 2 of TCR complex CD28
Signal 1 of B cells receptor Ig alpha and beta
Signal 2 of B cells receptor CD21
NKG2D receptors; CD94 inhibitory NK cells
Follicles in cortex B cells
Paracortex T cells
HLA defect, alkylating spondylitis HLA-B27

Ch. 8 – Viruses, Fungi, Protozoa

Reddish brown rash; Koplik spots Measles
Parotitis; orchitis Mumps
CD155 method of entry Polio
lethal with CCR5 defect West Nile Virus
Pink/purple intracellular inclusions HSV
Owl's eye/basophilic inclusion w/ halo CMV
Binds to CD21 (CR2) on B cells EBV
Atypical lymphocytes EBV
Threadlike filaments( hyphae) that grow and
Molds consist of? divide at their tips
Endemic mycosis are caused by? Dimorphic fungi
Who is susceptible to superficial candidiasis? Diabetics; Burn patients
In candida infection, what is an important determinant of virulence? Adhesion
What type of enzyme contributes to Candida invasiveness? Aspartyl proteinases
Promote tissue invasion by degrading
extracellular matrix proteins and catalases
which may enable resistance to oxidative
What is function of above? killing
Another virulence factor of Candida? Ability to grow biofilms
First line of defense against candida? PMN and Macs → oxidative killing
Filamentous forms → nonprotective Th2
Which form of Candida is more susceptible to destruction? response
Important diagnostic clue to candida? Pseudohyphae
Gomori Methenamine-Silver; Periodic acid-
Which types of stains are used for Candida? Schiff
Candida esophagitis presents how? Dysphagia and retrosternal pain
Most common fungal endocarditis? Candida endocarditis
Where is Cryptococcus neoformans found? Soil; Bird droppings (pigeon) → inhaled

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Polysaccharide capsule; Melanin production→
Virulence factors of C. neoformans? laccase Enzymes
Catalyzes the fomation of laccase →
What does laccase do? antioxidant properties
Serine protease→ cleaves fibronectin and BM
What types of proteins does C. neoformans produce? proteins
What type of fungi is C. neoformans? Yeast
Involve: meninges, cortical gray matter, and
basal nuclei → grow in Virchow Robbins
C. neoformans in the CNS? spaces = soap bubble lesions
Allergies; Sinusitis; Pneumonia; Invasive
What types of illness does Aspergillosis cause? disease
How are Aspergillus species transmitted? Airborne conida
Aflatoxin → grows on the surface of peanuts;
What carcinogen does Aspergillus produce? cause liver cancer in Africa

Morphology of Aspergillus infection? Masses of hyphae form brownish “fungal balls”

Immunosuppressed hosts → Target lesions-
necrotizing pneumonia with hemorrhagic
Invasive Aspergillus? borders
Aspergillus has a tendency to invade where? Blood vessels
“mucormycosis”; Bread-mold fungi →will affect
Zygomycosis? immunocompromised hosts
How are zygomycetes transmitted? Airborn asexual spores
Nonseptate, wide, fungal hyphae → right
Morphology of above? angle branching
Sites if zygomycosis invasion? Nasal sinuses; Lungs; GI
Rhinocerebral mucormycosis → spreading to
Common zygomycosis infection in diabetics? orbit and brain
How is malaria transmitted? Anopheles mosquito
Most severe type of malaria? P. falciparum
Sporozoite → found in salivary glands of
Infectious stage of malaria? female mosquitos
Sporozoite→ liver→ replicate→ release
merozoites→ RBC→ trophozoite→ schizont→
Life cycle of malaria? merozoite→ reinfect
Infect RBC of ANY age; Causes RBC to
clump= rosette→ block BF; Stimulate high
Important features of P. falciparum? levels of cytokines → INF-y, TNF, and IL-1
Which two Hgb mutations confer resistance to malaria? Heterozygous HbS; HbC
Some people do not have the Duffy Ag→
How are ppl resistant to P. vivax? allows entry to RBC
Fibrotic, brittle, and has thick capsule; Black
Look of spleen in chronic malaria infection? parenchyma
P. falciparum; Brain vessels are plugged by
Malignant cerebral malaria? parasitized RBC
Malarial/ Durck granulomas→ ring
What is found in above? hemorrhages
What is a reservoir for Babesia microti? White-footed mouse
Parasitize RBC and cause fever and hemolytic
Babesiae disease? anemia
What is diagnostic for Babesia organisms? Tetrads→ Maltese crosses
Shock; Hypoxia; Jaundice; Respiratory
distress syndrome; Visceral hemorrhages;
Severe symptoms of Babesia infection? Acute renal tubular necrosis
Promastigote→ extracellular flagellated
infectous Amastigote→ intracellular in MACS,
Stages of Leishmania? proliferate and infect
Lipophosphoglycan wil form glycocalyx →
How do Leishmania enter Macs? coat with C3b→ phagocytosis
What type of T cells are needed to control Leishmania infection? CD4+ helper T cells → Th1
What do above produce? High levels of IFN-y
Visceral Leishmania? L. donovani; L. chagasi → cause “black fever”
Cutaneous Leishmania? L. major; L. mexicana; L. braziliensis
Mucocutaneous Leishmania? L. braziliensis
Fevers; Lymphadenopathy; Splenomegally;
African trypanosomiasis? Sleeping sickness; Cachexia; Death
What transmits African Trypanosomiasis? Tsetse fly
Variant surface glycoprotein (VSG) → will
Pathogenesis of above? change constantly
Where are VSG found? Bloodstream expression sites → telomers
Bite→ capillaries of glomeruli or choroids
plexus→ breach BBB→ demyelinating
Mechanism of infection of Trypanosomiasis? panencephalitis

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Plasma cells containing cytoplasmic globules
Mott cells? filled with immunoglobulins
Trypanosoma cruzi? Chagas disease
Vector of above? Kissing bug → triatomids
Dilated cardiomyopathy; Arrhythmias;
What does chagas disease cause? Megacolon; Esophageal dysmotility
Chagas amastigotes create what in the heart? Intracellular pseudocysts
What does Strongyloidiasis cause? Autoinfection
Definitive host? Worm reaches sexual maturity
T. solium proglottids contain? Male and female reproductive organs
Convulsions; Increased ICP; Neurologic
What occurs with T. solium cysts in brain tissue? problems
Hydatid disease is caused by? Ingestion of eggs of echinococcal species
What are the definitive and intermediate hosts of E. granulosus? Definitive- dogs; Intermediate- sheep
Where are most E. granulosus cysts found? Liver
Degenerating scolices form what? Hydatid sand
Fever; Myalgias; Periorbital edema; Dysnpea;
Trichinosis causes? Encephalitis ; Cardiac failure
Trichinella stimulates what response? Th2; IL-4, IL-5, IL-10. IL-13
Where do Trichnella preferentially encyst? Striated skeletal ms → richest blood supply
What is useful for diagnosis in Trichnella? They leave behind calcified scars
Freshwater snails → tropical lakes and
Schistosomiasis is transmitted how? irrigation ditches
Will bite through skin→ lung→ mature in
hepatic vessels→ settle in portal or pelvic
Where do above settle? venous system
Immune response to above causes? Granuloma formation; Hepatic fibrosis

Pseudopolyps in the colon; Pipe-stem fibrosis;

What is found in severe Schistosomiasis infections? Cor pulmonale; Membranous glomerulopathy
Which type forms “calcified bladder”? S. haematonium
Lymphatic filariasis is transmitted by? Mosquitoes
Recurrent lymphadenitis; Elephantitis; Tropical
What does above cause? pulmonary eosinophilia
Adult parasites; Th1 mediated immune
response; IgE mediated Hypersensitivity→
Damage to the lymphatics is caused by? tropical
Small epitheliod granulomas → Meyers-
Types of granulomas in lung invovement? Kouvenaar Bodies
Onchecerca volvulus is transmitted by? Black flies
What is it treated by? Ivermectin
River blindness; Itchy dermatitis→ focal
What does it cause? darkening or loss of pigment and scaling

Ch. 26 – Joints, Soft Tissue Tumors

No space; fibrous or cartilagenous Solid (nonsynovial) Joints
Joint space; wide range of motion; synoviocytes; synovial fluid Cavitated (synovial) Joints
Type II collagen; no blood/lymph/nerves Hyaline Cartilage
Most common joint disease; women = knees/hands; men = hips Osteoarthritis
Usually oligoarticular; joint mice; bone eburnation (polished bone) Osteoarthritis
Worse with use; Heberden nodes in WOMEN Osteoarthritis
Chronic systemic inflammatory disorder; women 3x more than men Rheumatoid Arthritis
Pannus formation; Rheumatoid nodules in pressure areas Rheumatoid Arthritis
Usually symmetrical, small joints; MCP's and PIP's Rheumatoid Arthritis
Worse in morning/after inactivity Rheumatoid Arthritis
X-ray shows joint effusions; erosions; narrowing of joint space Rheumatoid Arthritis
Oligoarthritis + systemic disease + large joints first + no nodules Juvenile Idiopathic Arthritis
HLA-B27 allele Seronegative Spondyloarthropathies
Spinal immobility; spine fracture; ARTS1 and IL23R genes Ankylosing Spondyloarthritis
Arthritis + conjunctivitis + urethritis/cervicitis Reiter Syndrome
Sausage finger/toe Reiter Syndrome
Acute suppurative arthritis; Bacterial Arthritis
Monosodium urate crystals that are long, needle-shaped; tophi; Gout
Calcium pyrophosphate crystals are weakly birefringent w/ geometric shapes Pseudo-Gout
Mutation in ANKH gene for pyrophosphate transport channel Pseudo-Gout
“Pea near the wrist” Ganglion
Herniation of synovium through capsule or enlargement of bursa Synovial Cyst
Example of Synovial Cyst Baker's Cyst
t(1;2)(p13;q37); red-brown to mottled orange-yellow; usually in hand Tenosynovial Giant-Cell Tumor
Most common soft tissue tumor of adulthood Lipoma
Develop into large tumors; supernumerary rings; giant rod chromosomes Liposarcoma
Some lipoblasts always present Liposarcoma
Plump randomly oriented spindle cells surrounded by myxoid stroma Nodular Fascitis
Metaplastic bone; young athletes Myositis Ossificans
Rhabdomyoblast present; most common in embryo Rhabdomyosarcoma
Eccentric eosinophilic granular cytoplasm Rhabdomyoblast
Benign smooth muscle tumors; often in uterus Leiomyomas
Multiple cutaneous leiomyomas assoc'd with this... Renal Cell Carcinoma
Malignant spindle cells with cigar-shaped nuclei Leiomyosarcoma
Stain with antibodies to smooth muscle actin and desmin Leiomyosarcoma

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Ch. 26 – Joints, Soft Tissue Tumors

No space; fibrous or cartilagenous Solid (nonsynovial) Joints
Joint space; wide range of motion; synoviocytes; synovial fluid Cavitated (synovial) Joints
Type II collagen; no blood/lymph/nerves Hyaline Cartilage
Most common joint disease; women = knees/hands; men = hips Osteoarthritis
Usually oligoarticular; joint mice; bone eburnation (polished bone) Osteoarthritis
Worse with use; Heberden nodes in WOMEN Osteoarthritis
Chronic systemic inflammatory disorder; women 3x more than men Rheumatoid Arthritis
Pannus formation; Rheumatoid nodules in pressure areas Rheumatoid Arthritis
Usually symmetrical, small joints; MCP's and PIP's Rheumatoid Arthritis
Worse in morning/after inactivity Rheumatoid Arthritis
X-ray shows joint effusions; erosions; narrowing of joint space Rheumatoid Arthritis
Oligoarthritis + systemic disease + large joints first + no nodules Juvenile Idiopathic Arthritis
Seronegative
HLA-B27 allele Spondyloarthropathies
Spinal immobility; spine fracture; ARTS1 and IL23R genes Ankylosing Spondyloarthritis
Arthritis + conjunctivitis + urethritis/cervicitis Reiter Syndrome
Sausage finger/toe Reiter Syndrome
Acute suppurative arthritis; Bacterial Arthritis
Monosodium urate crystals that are long, needle-shaped; tophi; Gout
Calcium pyrophosphate crystals are weakly birefringent w/ geometric shapes Pseudo-Gout
Mutation in ANKH gene for pyrophosphate transport channel Pseudo-Gout
“Pea near the wrist” Ganglion
Herniation of synovium through capsule or enlargement of bursa Synovial Cyst
Example of Synovial Cyst Baker's Cyst
t(1;2)(p13;q37); red-brown to mottled orange-yellow; usually in hand Tenosynovial Giant-Cell Tumor
Most common soft tissue tumor of adulthood Lipoma
Develop into large tumors; supernumerary rings; giant rod chromosomes Liposarcoma
Some lipoblasts always present Liposarcoma
Plump randomly oriented spindle cells surrounded by myxoid stroma Nodular Fascitis
Metaplastic bone; young athletes Myositis Ossificans
Rhabdomyoblast present; most common in embryo Rhabdomyosarcoma
Eccentric eosinophilic granular cytoplasm Rhabdomyoblast
Benign smooth muscle tumors; often in uterus Leiomyomas
Multiple cutaneous leiomyomas assoc'd with this... Renal Cell Carcinoma
Malignant spindle cells with cigar-shaped nuclei Leiomyosarcoma
Stain with antibodies to smooth muscle actin and desmin Leiomyosarcoma

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