Path revision Flashcards
1
Q
Increase in the number of cells =
A
Hyperplasia
2
Q
Increase in the size of cells =
A
hypertrophy
3
Q
Cells that cant undergo hyperplasia - only hypertrophy
A
Cardiac muscle
Skeletal muscle
Nerve
4
Q
Conditions that don’t have and increased risk of cancer despite hyperplasia =
A
Benigh prostatic hyperplasia
Apocrine metaplasia
5
Q
Decrease in cell # occurs via
What changes occur in the cell during apoptosis
A
Apoptosis
decrease in size, red cytoplasm and condensed nucleus
6
Q
Decrease in cell size occurs via
A
Ubiquiten proteosome degradation
7
Q
Causes of metaplasia
A
Stress, Vitamin A deficiency,
8
Q
Dysplasia
A
Disordered cell growth/proliferation of precancerous cells
9
Q
Hallmark of reversible cell injury =
Hallmark of irreversible injury =
Hallmark of cell death =
A
cellular swelling
membrane damage
Loss of nucleus
10
Q
Necrosis =
what changes are seen in the cell?
Apoptosis =
causes of apoptosis - 2
A
Death of large groups of cells followed by ACUTE inflammation
cell swelling
Energy dependent (ATP) programmed cell death of single or small groups of cells - NO inflammation. - usually due to lack of oxygen or exposure to toxins/burns
Cell itself activates intrinsic enzymes that degrade the cells’ genomic DNA and nuclear and cytoplasmic proteins.
causes - 1 - normal physiological response 2- due to pathogenesis
eg cells with DNA damage
accumulation of misfolded proteins or due to infections
11
Q
Types of necrosis (6)
A
1 - Coagulative - cell shape & organ structure preserved - localised area of coagulative necrosis = infarct (doe not occur in brain)
2 - Liquefactive - brain infarct , abscess, pancreatitis
3- Gangrenous - coagulative necrosis that resembles mumified tissue
4 - Caseous - soft friable necrotic tissue - cheese like - combo of coagulative and liquefactive - TB fungal
5- Fat necrosis - pancreatitis +/- saponification
6 - Fibrinoid - necrotic damage to blood vessel
12
Q
Apoptosis is mediated by ?
and activated by multiple pathways ?`
A
Caspases
Intrinsic mitochondrial pathway
Extrinisc receptor - ligand pathway
Cytotoxic CD8 T cell mediated pathway
13
Q
Free radicals cause damage via
Elimination is via
A
Peroxidation of lipids
Oxidation of DNA proteins
Antioxidants - glutathionine, Vit A, C and E
14
Q
Amyloid =
Can be systemic or local
A
misfolded protein which deposits in the extracellular space
Beta pleated sheet configuration
Congo red stain and green apple birefringence
15
Q
Primary amyloid =
Secondary amyloid =
A
AL amyloid - associated with MM derived from immunoglobulin light chain
AA amyloid - derived from serum amyloid protein
16
Q
Inflammation -
Acute or chronic
Acute inflammation mediators?
A
Acute - Oedema and neutrophils
Chronic - Lymphocytes and plasma cells
Toll like receptors
Arachidonic acid metabolites
Mast cells
complement
Hageman Factor (F12)
17
Q
Neutrophil arrival and function
A
Margination
Rolling
Adhesion
Transmigration and chemotaxis
Phagocytosis
Destruction of phagocytosed material
Resolution
18
Q
Neutrophils are attracted by bacterial products - ?
A
IL-8
C5a
LTB4
19
Q
Chronic granulomatous disease =
A
poor o2 dependent killing which leads to recurrent infection and granuloma formation with catalase positive organisms - KNOW
- staph aureus
- pseudomonas cepacia
- Serratia marcescens
- No cardia
- Aspergillus
20
Q
What test is done to screen for CGD?
A
Nitroblue tetrazolium
21
Q
T lymphocytes
A
Produced in the BM as progenitor T cells and further develop in the thymus where they undergo rearrangement and become CD4+ helper T cells or CD8+ cytotoxic T cells
T cells use TCR complex for antigen surveillance
22
Q
T lymphocytes
A
Produced in the BM as progenitor T cells and further develop in the thymus where they undergo rearrangement and become CD4+ helper T cells or CD8+ cytotoxic T cells
T cells use TCR complex for antigen surveillance
CD8+ t cells - killing occurs via secretion or perforin
23
Q
Granuloma =
Caseous granuloma
Non caseous granuloma
A
Collection of epitheliod histiocytes surrounded by giant cells and rim lymphocytes
Caseating - central necrosis - TB or fungal
Non-caseating - no central necrosis - FB, sarcoid, beryllium, Crohns, Cat scratch
24
Q
Primary immunodeficiencies (8) -
Di George
Severe combined immunodeficiency
x-linked agammaglobulinemia
Common variable immunodeficiency (CVID)
IgA deficiency - MOST COMMON
Hyper IgM syndrome
Wiskott-Aldrich syndrome
Complement deficiency
A
Di George = failure of the 3rd and 4th pharyngeal pouches to form normally. 22q11 microdeletion.
Tcell deficiency - lack of thymus and parathyroids
SCID - defective cell mediated and humoral immunity
x-linked agamma - complete lack of immunoglobulin - due to disordered B cell maturation. mutated BRUTON TYROSINE kinase
CVID - low immunoglobulin due to B cell or helper T cell defect
IgA def - low serum and mucosal IgA
Hyper IgM syndrome - Elevated IgM - mutated CD40 on T helper cells or CD40 receptor on B cells. Low IgA, IgG and IgE
Wiskott - Thrombocytopenia
Mutation in the WASP gener
Complement defi - C5-C9 deficiencies - Increased risk of Neisseria infection. C1 inhibitor deficiency - angiooedema
25
Autoimmune disorders (4)
SLE
Sjogrens
Scleroderma
Mixed connective tissue disease
26
SLE =
Antibodies against host damages multiple tissues via type 2 and 3 HS reaction.
LIBMAN-SACKS - endocarditis - small sterile deposits BOTH sides of the valve
27
SLE =
Antihistone antibody is common in drug induced SLE
Association?
Systemic autoimmune disease
Antibodies against host damages multiple tissues via type 2 and 3 HS reaction.
LIBMAN-SACKS - endocarditis - small sterile deposits BOTH sides of the valve
Characterised by ANA and AntidsDNA antibodies
Associ - Antiphospholipid antibody syndrome
28
Sjogrens syndrome
Autoimmune destruction of lacrimal and salivary glands
Lymphocyte mediated damage - Type IV HS with fibrosis
29
Sjogrens syndrome
Associated with ?
Autoimmune destruction of lacrimal and salivary glands
Lymphocyte mediated damage - Type IV HS with fibrosis
Characterised by ANA and antiribonucleoprotein antibodies
Assoc - rheumatoid arthritis
Increased risk for marginal zone B cell lymphoma (MALT)
30
Scleroderma
Diffuse or localised
Diffuse =
Localised =
Autoimmune tissue damage with activation of fibroblasts and dposition of collagen (fibrosis)
Diffuse - skin and early visceral involvement. Eosophagus common.
Characterised by ANA and AntiDNAtopoisomerase I antibody
Localised - skin + late visceral involvement
CREST syndrome
31
Mixed connective tissue disorder.
Autoimmune mediated tissue damage with mixed features of SLE, systemic sclerosis and systemic sclerosis, polymyositis
Characterised by serum antibodies against U1 ribonucleoprotein
32
Granulation tissue is made up of -
What removes type III collagen?
What is required as a co factor?
Fibroblasts (deposits Type III collagen), capillaries and myofibroblasts.
Collegenase
Zinc
33
Cutaneous healing occurs via?
Primary or secondary intention
34
Clonality of cells is determined by ?
Clonality of Blymphocytes is determined by
G6PD or
androgen receptor isoforms
Ig (light chains)
35
Most common adult ca by incidence?
Mortality?
incidence - 1 = brst/prostate
2 = lung 3 = colorectal
Mortality - 1 = lung 2 = brst/prostate 3 = colorectal
36
DNA damage disrupts key regulatory systems
1) proto-oncogenes
2) Tumour suppresor genes
3) Regulators of apoptosis
Proto-oncogenes - GF, GFR, signal transducer, nuclear regulators, cell cycle regulators
Tumour supressor genes - P53 and Rb (retinoblastoma)
both regulate progression of cell cycle from G1 to S phase.
37
Li Fraumeni syndrome
Germline mutation of P53
leads to multiple types of carcinomas and sarcomas
38
Sporadic mutation of RB =
Germline mutation of RB =
Unilateral retinoblastoma
Bilateral retinoblastoma and osteosarcoma
39
Bcl2 - normally stablisizes mitochondrial membrane blocking release of cytochrome C (activates apoptosis)
Bcl2 is over expressed in
FOLLICULAR LYMPHOMA
40
Lymphatic spread is characteristic of ?
Haematogenous spread is characteristic of ?
Carcinomas
Sarcomas and some carcinomas
- HCC
- RCC
- follicular ca of the thryoid
- choriocarcinoma
41
Primary and secondary haemostasis
Primary =
Secondary =
P = weak platelet plug mediated by interaction of platelets with vessel wall
S = stablises platelet plug mediated by coagulation cascade.
42
vWF is derived from ?
Weibel palade bodies of endothelial cells and alpha granules of platelets
43
Primary haemostasis disorders
2 Quantitative and 4 qualitative
ITP - immune thrombocytopenic purpura - MOST COMMON cause of thrombocytopenia in children and adults - autoimmune production of IgG against platelets
Microangiopathic haemolytic anaemia - pathologic microthrombi in small vessels - schistocytes. Seen in TTP and HUS
TTP - Decreased ADAMTS13 (cleaves vWF)
HUS - E.coli O157:H7 dysentry
- Bernard-Soulier syndrome - GP1b deficiency
- Glanzmann thrombasthenia - GPIIb/IIIa def
- Aspirin
- Uremia
44
Secondary haemostasis disorders (5)
Factors for coag cascade requires exposire to activating substances -
Tissue thromboplastin (activates F7) - ext
Subendothelial collagen (activates F12) - intrins
Haemophilia A (F8) deficiency
Haemphilia B (F9) deficiency
Coag factor inhibitor - acquired antibodies against coag factors - anti factor 8 most common
Von Willebrand disease - most common inherited disorder
Vit K deficiency - activates by epoxide reductase in the liver
Other = liver failure, large vol transfusion
45
Other disorders of haemostasis
Heparin induced thrombocytopenia
DIC - pathologic activation of cascade
46
Disorders of fibrinolysis
Fibrinolysis normally removes thrombus after vessel has healed
usually due to overactivitiy of PLASMIN - enzyme that destroys blood clots by attacking fibrin.
Radical prostatectomy - released urokinase which activates PLASMIN
Cirrhosis - decreases production of alpha 2-antiplasmin
(normally inactivates plasmin)
47
Thrombus is characterised by ? (2)
Lines of Zahn
Attachment to vessel wall.
48
Causes of endothelial damage = ?
What results in elevated homocysteine?
homocysteine = type of aa used to make proteins - normally vit B12, B6 and folic acide breaks it down and very little should be in blood stream.
atherosclerosis, vasculitis, high homocysteine levels
Vit B12 and folate deficiency
cystathionine beta synthase deficiency (SB)
49
Hypercoagulable state causes ?
Protein C or S deficiency
Factor V Leiden deficiency
Prothrombin 2010A
ATIII deficiency
OCP
50
Anaemia =
Based on MCV anaemia is classified as microcytic, normocytic or macrocytic
Decreased circulating RBC mass
Hb < 13.5 g/dl in males
Hb < 12.5 g/dl in females
MCV < 80 = microcytic
MVC 80 - 100 = normocytic
MVC > 100 = macrocytic
51
Microcytic anaemia - decreased production of Hb
Hb =
Types if microcytic anaemia ? (4)
Hb = heme + globulin
Heme = iron + protoporphyrin
Iron defic anaemia
Anaemia of chronic disease
Sideroblastic anaemia
Thalaseamia
52
Iron defic aneamia - iron is absorbed in the ?
What transports iron in blood?
How is iron stored?
What is Plummer vinson syndrome ?
Duodenum
via Transferritin
Bound to ferritin
iron def anaemia with eosophageal web, atrophic glossitis. Presents with anemia, dysphagia and beefy red tongue
53
Anaemia of chronic disease - chronic disease results in production of acute phase reactants from liver called ?
HEPCIDIN - sequestres iron in storage sites by 1) limiting iron transfer from macrophages to erythroid precursors and suppressing EPO production
54
Sideroblastic anaemia
Due to defective protoporphyrin synthesis
iron remains trapped in mitochondria and form a ring around the nucleus or erythroid precursors aka ringed sideroblasts
Can be congenital - ALAS
or acquired - alcohol, lead poisoning, Vit B6 deficiency
55
Thalassemia =
Carriers are protected against?
Decreased synthesis of globin chains of Hb
Plasmodium falciparum malaria
56
Thalassemia is divided into alpha and Beta globin chains
Normal types of Hb =
Alpha thalassemia is due to ?
Beta thalassemia is due to ?
minor and major
Cis deletion =
trans deletion =
HbF
HbA
HbA2
gene deletion
gene mutation
Minor -> reduced HbA, increased HbF and HbA2
Major -> NO HbA, increased HbF and HbA2
cis = both deletions on the same chromosome
trans = one deletion on each chromosome
57
Erythroid hyperplasia results in
(beta thalassemia major)
expansion of haematopoeiesis into skull and facial bones
extrameduallry haematopoeisis + hepatosplenomegaly
Increased risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
nucleated RBC + target cells
58
Causes of macrocytic anaemia
Where is folate absorbed?
what do you see/get with folate deficiency ?
Where is Vit B12 absorbed ?
What do you see/get ?
Amylase (saliva) releases B12 which binds to R-binder and carried to stomach. Pacreatic proteases in duodenum detach Vit B12 from R-binder. Vit B12 bind to intrinsic factor (released by parietal cells - gastric)
intrinsic factor - Vit B12 is then absorbed in______
Causes of B12 deficiency ?
Disorders?
Folate or vitamin B12 deficiency
Jejunum
Large RBC and hypersegmented neutrophils
Reduced serum folate
Increased serum homocysteine
NORMAL methylmalonic acid
Terminal ileum
Pernicious anaemia - macrocytic RBC + hypersegmented neutrophils
Autoimmune destruction of parietal cells = intrinsic factor defi
Pancreatic insufficiency
Damage to terminal ileum (crohns, fish tapeworm)
Diet - rare
Subacute degeneration of the spinal cord
Low serum B12
High serum homocysteine
INCREASED METHYLMALONIC ACID
59
Normocytic anaemia is due to ?
How do you distinguish it from eachother ?
increased peripheral destruction or underproduction
Reticulocyte count - normal 1-2 %
if bone marrow responds by increasing RC to > 3% then there is good response and means peripheral destruction
Corrected count < 3% means poor response and suggests underproduction
60
Peripheral RBC destruction can be intravascular or extravascular
Extravascular causes ?
Hereditary spherocytosis - defect in the RBC cytoskeleton membrane
HOWELL-JOLLY bodies seen on bld smear
Sickle cell anaemia
61
Sickle cell anaemia =
Results in ?
Sickle cell disease vs trait
Autosomal recessive mutation in the beta chain of Hb
Single AA change replaces normal glutamic acid with VALINE
Haemaglobin C - glutamic acid is replaced by LYSINE
extravascular and intravascular haemolysis
Expansion of haematopoeisis into skull
Extramedullary haematopoeisis + hepatomegaly
Risk of aplastic crisis with parvovirus B19
irreversible sickling --> dactylitis, autosplenectomy which increases risk of infection with encapsulated organisms such as strep pneum, H. influenzae
increases risk of salmonella paratyphi osteomyelitis
HOWELL JOLLY bodies
Sickle cell disease = 90% HbS, 8% HbF, 2% HbA2, NO HbA
Sickle trait = 55% HbA, 43% HbS, 2% HbA2
62
Causes of predominant intravascular haemolysis ? (5)
PNH
G6PD defic
Immune haemolytic anaemia (IHA)
Microangiopathic haemolytic anaemia
Malaria
What test is used to screen for PNH?
Main cause of death?
Complications include? (2)
Paroxysmal nocturnal haemoglobinuria = defect in myeloid stem cells resulting in absent GLYCOSYLPHOSPHATIDYLINOSITOL (GPI) which renders cell susceptible to destruction by complement
Decay accelerating factor (DAF) - normally protects cell from this. GPI secures DAF to cell membrane
Absence of GPI = absence of DAP - cell susceptible to complement mediated damage
Sucrose test - detects lack of CD 55 (DAF) on cell membrane
Thrombosis of hepatic, portal, or cerebral veins
(destroyed platelets release cytoplasmic contents into circulation inducing thrombosis
iron def anaemia and AML
63
Glucose 6 phosphate dehydrogenase deficiency =
What is used to screen for disease ?
xlinked recessive disorder resulting in reduced half life of G6PD - renders cells susceptible to oxidative stress
H2O2 (oxidative stress) neutralised by glutathionine (antioxidant) normally which becomes oxidized in the process
2 variants - African - mild
Mediteranean - marked reduced half life of G6PD
Oxidative stress precipitates Hb as HEINZ bodies HEINZ bodies are removed by splenic macrophages resulting in bite cells
Heinz preparation is used to screen for disease
64
Immune haemolytic anaemia =
What test is used to screen for it ?
Antibody-mediated destruction of RBC's (IgG or IgM)
IgG - usually extravascular haemolysis
IgM - usually intravascular haemolysis
IgG binds RBS in warm environment (warm aggluttinin)
Assoc with SLE, CLL and certain drugs (penicillin and cephalosporin)
IgM (cold aggluttinin)
Assoc with mycoplasma pneum and infectious mono
COOMBS test - direct or indirect
Directs confirms presence of antibody coated RBCs. Anti IgG is added to patients RBCs and aggluttination occurs if RBCs already coated with antibody
Indirect - Confirms presence of antibodies in patients serum.
65
Microangiopathic haemolytic anaemia =
intravascular haemolysis due to vascular pathology. RBCs are destroyed as they pass through circulation.
Occur with microthrombi due to TTP-HUS, DIC and HELLP. , prosthetic heart valves and aortic stenosis
Produce schistocytes on blood smear
66
Malaria =
P.Falciparum = daily fever
P vivax and P ovale = fever everyother day
Infection of RBC and liver with Plasomodium transmitted by female Anopheles mosquito
RBCs rupture as part of life cycle. resulting in intravascular hemolysis and cyclical fever
spleen also consumes some infected RBCs resulting in mile extravascular hemolysis with splenomegaly.
67
Anaemia due to underproduction (3)
Parvovirus B19 - infects progenitor red cells and temporarily halts erythropoeisis. Results in significant anaemia in the setting pf pre-existing marrow stress (eg sickle ell)
Anaplastic anaemia - damage to haematopoeitic stem cells resulting in pancytopenia and low reticulocyte count . biospy shows empty fatty marrow
Myelophthisic process - pathologic process that replaces BM. Haematopoeisis is impaired resulting ni pancytopenia
68
Infectious mononucleosis
EBV infection lymphocytic leukocytosis - reactive CD8+ T cells. CMV less common cause
69
Acute leukaemia =
Can be further subdivided into ALL and AML.
Neoplastic proliferation of of blasts - >20% of blasts in BM which crowds out the normal haematopoeisis.
Blasts are large immature cells with punched out nuclei
70
ALL =
MOST COMMON in children and assoc with Downs
Subclassified into B-ALL and T-ALL based on surface markers
B-ALL is most common type of ALL.
neoplstic accumulation of lymphoblasts (>20% in BM)
lymphoblasts are positive nuclear staining for TdT+ (usually absent in myeloid blasts and mature lymphocytes)
B-ALL is characterised by lymphoblasts that express CD10, CD19 and CD20.
Prognosis based on cytogenic abnormalities
t(12;21) good prognosis seen in children
t(9;22) poor prognosis seen in adults (philideplhia + ALL)
T-ALL is characterised by lymphoblasts postive for Tdt+ and express CD2-CD8 markers - NO CD10
usually presents in teenagers with mediastinal mass.
71
AML =
Subclassified into APL (acute promyelocytic leukaemia)
Acute monocytic leukaemia - lack MPO
Acute megakeryoblastic leukaemia - lack MPO. Assoco with downs syndrome
Neoplastic accumulation of myeloblasts (>20% in BM)
Usually positive staining for myeloperoxidase (MPO)
seen in ilder adults (50-60) Crystal aggregate on MPO may be seen as AUER RODS
72
Chronic leukaemia =
Subtypes -
CLL,
Hairy cell,
ATLL,
Mycosis fungoides
Neoplastic proliferation of mature circulating lymphocytes
Characterised by a high WBC count. Seen in older adults
CLL = neoplastic proliferation of Naive B cells that express CD5 and CD20.
MOST COMMON leukaemia overall
Hairy cell leukaemia = Neoplastic proliferation of MATURE B cells. Cells are + for TRAP.
splenomegaly - NO lymphadenopathy.
Adult T cell Leukaemia/lymphoma - Neoplastic proliferation of mature CD4+ T cells
Assoc with ATLV-1
Mycosis Fungoides = neoplastic proliferation of mature CD4+ T cells that infiltrate the skin, producing a rash, plaques and nodules.
Aggregates in epidermis = Pautrier Microabscesses
cells can spread to the blood causing Sezary syndrome
73
Myeloproliferative disorders included
CML
PV
Essential thrombocytopenia
Myelofibrosis
CML =
Polycethemia Vera =
Essential thrombocytopenia =
Myelofibrosis =
Neoplastic proliferation of mature myeloid cells. Driven by the philidelphia chromosome t(9;22)
Neoplastic proliferation of mature myeloid cells - esp RBCs (granulocytes and platelets also increase)
Assoc with JAK2 kinase mutation.
Neoplastic proliferation of mature myeloid cells, esp platelets. (RBC and granulocytes also increase)
Assoc with JAK 2 kinase mutation
Neoplastic proliferation of mature myeloid cells - esop megakaryocytes. Causes marrow fibrosis. Splenomegaly due to extramedullary haematopoeisis
Assoc with JAK2 kinase mutation
74
Lymphadenopathy
painful - acute infection
painless - chronic infection, mets, ca, lymphoma
In inflammation, lymph node enlargement is due to hyperplasia of particular regions of the lymph node
Follicular =
Paracortex =
Sinus histiocytes =
hyperplasia of B cell region - seen in Rheum arth and early HIV
hyperplasia of T cell region seen in viral infections
hyperplasia due to draining of tissue with cancer
75
Lymphoma is neoplastic proliferation of lymphoid cells that form a "mass" may arise in a lymph node or in extranodal tissue.
Divided into
Hodgkin (40%) and Non-Hodgkin (60%)
What are the malignant cells for each?
NHL is further classified into B or T cell
Small B cells =
Intermediate B cells =
Large B cells =
NHL = lymhoid cells
HL = Reed -sternberg cells
Small B cells = follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and small lymphocytic lymphoma
Intermediate = Burkitts lymphpma
Large = Diffuse large B cell lymphpma
76
NHL
Follicular lymphoma =
Mantle cell lymphoma =
Marginal zone =
Neoplastic proliferation of small B cells (CD20+) that form follicle like nodules. Overexpression in Bcl2
Neoplastic proliferation of small B cells (CD20+) expands the mantle zone. PResents in late adulthood with painless LAD. overexpression of cyclin D1
Neoplastic proliferation of small B cells that expands the marginal zone. Assoc with chronic inflammation states. MALToma = marginal zone lymphoma in mucosal sites
77
Burkitt lymphoma
neoplastic proliferation of intermediate sized B cells
Assoc with EBV.
presents as extranodal mass in child or young adult
African form = Jaw
Sporadic form = Abdo
overexpression of c-myc oncogene
78
Diffuse large B cell =
Neoplastic proliferation of large B cells (CD20+) that grow diffusely in sheets.
MOST COMMON form of NHL
Sporadic or transformation of low grade lymphoma (follicular)
79
HODGKINS lymphoma =
Subtypes
Nodular sclerosis - MOST COMMON
Lymphocyte rich - best prognosis
Mixed cellularity - abundant eosinophils
Lymphocyte depleted - most aggressive
Neoplastic proliferation of REED-STERNBERG cells
which are large B cells with multilobed nuclei and prominent nucleoli - positive for CD15 and CD30
80
Plasma cell disorders - Dyscrasias
Multiple myeloma =
MGUS =
Waldenstrom Macroglobulinemia =
MM = malignant proliferation of plasma cells in BM
MOST COMMON malignancy of bone, metastatic ca
High serum IL-6
features - bone pain, hypercalcaemia, M -spike on electrophoresis, increased risk of infection, primary AL amyloid. Bence jones proteins (free light chains in urine)
MGUS - High serum protein with M-spike but NO OTHER features of MM.
5% of 70 yr olds. 1% develop MM each year.
Waldenstrom = B cell lymphoma with monoclonal IgM production. Generalised LAD, lytic bone lesions ABSENT
High serum protein with M-spike
81
LCH - specialised dendritic cells found predominantly in the skin. Derived from BM monocytes
Subtypes
Lettere-Siwe disease
Eosinophilic granuloma
Hand Schuller-Christian disease
neoplastic proliferation of Langerhans cells
Characteristic Birbeck granules
cells are CD1a + and S100
Lettere-Siwe disease = malignant proliferation of Langerhans cells - skin rash, cystic skeletal defects in infant, may be fatal
Eosinophilic granuloma = Benign proliferation of Langerhans cells in bone. Can present as pathological fracture in adolecent
Hand-Schuller-Christian disease = Malignant proliferation of Langerhans cells. Scalp rash, lytic skull defects, Diabetes insipidus
Exopthalmos in children.
82
Vasculitis
Large vessels =
Medium vessels =
Small vessels =
Large - aorta and branches
Temporal giant cell arteritis
Takayasu
Medium vessel - Muscular arteries supplying organs
Polyarteritis Nodosa
Kawasaki disease
Buerger disease
Small - arterioles, capillaries and venules
Wegners granulomatosis
Microscopic polyangitis
Churg Strauss
Henoch Schonlein Purpura
83
Temporal arteritis =
Takayasu =
MOST COMMON form - adults > 50 F>M
Headache, visual dist, jaw claudication, polymyalgia rheum, high ESR
Granulomatous arteritis involving arch and branches - adults <50 yrs yng asian female
Visual and neurologic symptoms with weak absent pulses in upper extremity (pulseless disease)
ESR increased
84
Polyarteritis Nodosa =
Kawasaki disease =
Buerger Disease =
Necrotising vasculitis - mutleiple organs - LUNGS SPARED
Yng adult with HTN
Abdo pain with melena
Neurologic dist and skin lesions
Assoc with serum HBsAg
STRING OF PEARLS sign - heals with fibrosis
Asian children < 4 yrs
fever, conjunctivitis, erythem rash of palms/soles, enlarged cervical lymphnodes
CORONARY art involvement
- thrombosis, MI, aneurysm/rupture
Necrotising vasculitis involving digits
Ulcertaion, gangrene, autoamput of fingers/toes
Highyl assoc with smoking
85
Wegeners Granulomatosis =
Microscopic polyangitis =
Churg Strauss =
Henoch-Schonlein purpura =
necrotising granulomatous vasculitis involving nasopharynx, lungs, kidneys
Middle aged male with sinusitis or nasopharyngeal ulceration
Haemoptysis, bilateral nodular lung infiltrates, haematuria
C-ANCA positive
Necrotising vasculitis of multiple organs esp lung and kidney
P-ANCA positive
same presentation/treatement as wegners
Necrotising granulomatous inflamma with eosiniphils involving multiple organs, esp lung and heart
Asthma plus peripheral eosinophilia
P-ANCA positive
Vaculitis due to IgA immune complex deposition
MOST COMMON vasculitis in children
Palpable purpura on buttocks + legs
GI pain and bleeding and haematuria (IgA nephropathy)
Usually following upper resp infection
Self limited
86
HTN - primary and secondary
Arteriosclerosis - 3 patterns
Atherosclerosis
Arteriolosclerosis - divided into ?
Monckeberg medial calcific sclerosis = ?
Hyaline and hyperplastic
Hyaline = proteins leak into vessel wall producing vascular thickening - cause = long term HTN or DM
Hyperplastic = hyperplasia of smooth muscle cause = malignant HTN
Monckeberg - calcification of media of muscular arteries - NON obstructive - not clinically significant
87
Vascular tumours
Hemangioma - benign
Angiosarcoma - malignant proliferation of endothelial cells
Kaposi Sarcoma = ?
low grade malignanct proliferation of endothelial cells
Assoc with HHV-8
Purple patches, plaques and nodules on skin
88
Stable angina = ?
Unstable angina = ?
Prinzmetal angina = ?
CP with exertion or emotional stress. Due to atherosclerosis of coronary artery >70% stenosis
Subendocardial ischaemia - ST depression
CP at rest - due to rupture of plaque and thrombosis/incomplete occlusion of vessel
Subendocardial ischaemia - ST depression
Episodic CP unrelated to exertion
Due to coronary art vasospasm
ST elevation due to transmural ischaemia
89
LAD occlusion leads to infarct where?
RCA?
Left circumflex?
Troponin I for MI
CK MB used for ?
Ant wall and ant septum
Post wall and post septum
Lateral wall of LV
detecting reinfarction - normalised as 72 hrs
90
Congenital heart defects
VSD
ASD
PDA
TOP
Transposition
Truncus arteriosus
Tricuspid atresia
Coarctation - adult and child forms
Large VSD can lead to Eisenmenger syndrome
ASD - normally ostium secundum (90%) - primum assoc with Downs
PDA assoc with congenital rubella
TOF - Stenosis of RV outflow tract, RV hypertrophy, VSD and aorta that overides VSD.
Transposition - assoc with maternal diabetes
Truncus arteriosus - single large vessel arising from both ventricles
Tricuspid atresia - RV hypoplastic
Coarctation - infant - assoc with PDA. Distal to arch but before PDA
Adult - distal to arch but no PDA
91
Rheumatic fever = ?
Systemic complication from pharyngitis due to group A B hemolytic strep
2-3 weeks after strep pharyngitis
Bacterial M protein mimics proteins in human tissue
Dx based on Jones criteria
Evidence of previous grp A B haemolytic strep infection (elevated ASO or anti DNAse B titres) + major and minor criteria
Minor = fever, elevated ESR - non specific
Major = Migratory polyarthritis
Pancarditis - infection of all three layers
Subacute nodules
Erythema maginatum
92
Endocarditis -
bacteria and what they affect
Strep viridans
Staph aureus
Stap epidermidis
Strep bovis
HACKE
Strep viridans = low virulence MOST COMMON infects previously damaged valves . Small vegetations dont destroy valve
Stap aureus = high virulence - IV drug use - infects normal valves - TRICUSPID. Large vegetations destroy valve.
Stap epidermidis - assoc with prosthetic valves
Strep bovis - associated with underlying colorectal ca
HACEK group - negative blood cultures
93
Types of cardiomyopathies
Dilated
Hypertrophic
Restrictive
Dilated - dilatation of all 4 chambers. MOST COMMON. Systolic dysfunction due to idopathic cause
Hypertrophic - Massive hypertrophy of left ventricle - due to sarcomere protein mutation
Restrictive - causes; amyloid, sarcoid, haemochromatosis, endocardial fibroelastosis, Loeffler syndrome
94
Cardiac Tumours
Myxoma
Rhabdomyoma
Metastases
Myxoma - benign- MOST COMMON in ADULTS
pedunculated, left atrium
Rhabdomyoma - Benign - MOST COMMON in CHILDREN. Assoc with TS
Ventricle
Mets - breast, lung, melanoma, lymphoma
Pericardium --> effusion
95
Rhinitis = ?
Most common cause ?
Subtype = allergic rhinitis
inflammation of the nasal mucosa
Adenovirus
Type 1 HS characterised by eosinophils, assoc with asthma and eczema
96
Nasal polyp - secondary to recurrent bouts of rhinitis and also in CF and aspirin intolerant asthma
Aspirin intolerant asthma characterised by triad of asthma, aspirin induced bronchospasm and nasal polyps
97
Juvenile nasopharyngeal angiofibroma
Benign tumour of nasal mucosa - locally aggressive
adolescent males
Vividly enhancing soft tissue mass centered on the sphenopalatine foramen
prominent flow voids with salt and pepper appearance
98
Nasopharyngeal carcinoma = ?
Malignant tumour of nasopharyngeal epithelium
Assoc with EBV
99
Epiglottis =
inflammation of the epiglottis - most common cause = H. influenzae type B.
100
Croup =
inflammation of the upper airway - most common cause = parainfluenzae virus
101
Laryngeal papilloma
benign papillary tumour of the vocal cord. Due to HPV 6 and 11.
102
Laryngeal carcinoma
Squamous cell carcinoma arising from epithelial lining of the vocal cord. Risk factors are alcohol and tobacco.
103
Lobar pneumonia
Classic phases of lobar pneumoniae?
Usually bacterial - most common causes are streptococcus pneumoniae (95%) and Klebsiella pneumoniae
Congestion - due to congested vessels and oedema
Red hepatization - due to exudate, neutrophils and haemorrhage
Gray hepatization - due to degradation of red cells in the exudate
Resolution
104
Bronchopneumonia
Scattered patchy consolidation centered around the bronchioles; often multifocal and bilateral
105
TB due to inhalation of Mycobacterium tuberculosis
Primary and secondary
primary =
secondary =
Primary arises with initial exposure
focal caseating necrosis in the lower lobe and hilar lymph nodes that undergo fibrosis and calcification forming Ghon complex
Secondary arises with reactivation of Mycobacterium tuberculosis.
reactivation is commonly due to AIDS or ageing
Occurs at the apex
Forms cavitary foci of caseous necrosis and may lead to miliary TB or bronchopneumonia
AFB stain - acid fast bacilli
Systemic spread often occurs and can involve any tissue.
106
COPD
Chronic bronchitis =
Emphysema =
Asthma and bronchiectasis
Group of diseases characterised by airway obstruction; lung does not empty and air is trapped.
chronic productive cough lasting atleast 3 months over a minimum of 2 years - highly assoc with smoking
characterised by hypertrophy of bronchial mucinous glands - leads to increased thicknedd of mucus glands relative to overall bronchial wall thickness
(REID INDEX increases to > 50%; normal is <40%)
Destruction of alveolar air sacs
Due to imbalance between proteases and antiproteases
Smoking is most common cause
A1AT is rare cause - results in pancinar emphysema in the lower lobes
107
Pulmonary hypertension =
Primary and secondary
high pressure in the pulmonary circuit (>25 mm Hg , normal <10 mm Hg.
Characterised by atherosclerosis of the pulmonary trunk, smooth muscle hypertrophy of pulmonary arteries and intimal fibrosis.
Primary - young adult females
cause unknown.
Secondary - due to hypoxemia or increased volume in the pulmonary circuit. May also arise due to recurrent PE's.
108
RDS =
Neonatal RDS =
whats used to test for lung maturity ?
neonatal RDS is associated with?
Acute RDS - diffuse damage to the alveolar-capillary interface. Leakage of protein rich fluid leads to oedema and formation of hyaline membranes in alveoli.
Due to inadequate surfactant levels. Made by type II pneumocytes. phosphatidylcholine (lecithin) is the major component. surfactant normally decreases surface tension in the lung, preventing collapse of alveolar air sacs after expiration. Lack of surfactant leads to collapse of air sacs and formation of hyaline membranes.
amniotic fluid lecithin to sphingomyelin ratio
lecithin levels increase if surfactant is produced.
ratio of >2 = adequate production
Prematurity, C-section, maternal diabetes
109
Lung Cancer - key risk factors = smoke, radon and asbestos
divided into 2 categories - ?
Small cell ca (15%) - NOT amenable to surgery - treated with chemo
Non small cell ca (85%) - surgical resection, does not respond well to chemo.
subtypes include;
- adenocarcinoma (40%)
- squamous cell carcinoma (30%)
- large cell carcinoma (10%)
- carcinoid tumour (5%)
110
Staging of lung ca is based on ?
Tumour size and local extension
pleural involvement classically seen with adenocarcinoma
Obstruction of SVC
involvement of recurrent laryngeal or phrenic nerve
Compression of sympathetic chain leads to Horner syndrome
Spread to regional lymph nodes
unique site of distal mets = ADRENAL gland
111
Cancer histology association location comment
Small cell carcinoma
Squamous cell
Adenocarcinoma
Large cell
Bronchoalveolar
Carcinoid
Metastasis
neuroendocrine cells, male smokers, central, rapid growth and early mets. may produce ADH or ACTH or cause Eaton-Lambert syndrome (paraneoplastic syndrome)
keratin pearls or intracellular bridges, male smokers, central, may produce PTHrP
Glands or mucin, non smokers, female, central or peripheral
poorly differentiated large cells, smoking, central or peripheral, poor prognosis
Columnar cells that grow along pre existing brocnhioles and alveoli, Not smoking related, peripheral, pneumonia like consolidation, excellent prognosis
Neuroendocrine cells, chromagranin positive, not smoking related, central or peripheral, polyp like mass in bronchus. Low grade malignancy, rarely can cause carcinoid syndrome
most common source is breast and colon carcinoma
multiple cannon ball like nodules on imaging. more common than primary tumours.
112
Pleural lesions
Pneumothorax - accumulation of air in the pleural space.
Mesothelioma - malignant neoplasm of mesothelial cells
113
Aphthous ulcer =
Bechet syndrome =
Painful superficial ulceration of the oral mucosa
arises in relation to stress and resolves spontaneously
Recurrent aphthous ulcers, genital ulcers and uveitis. Due to immune complex vasculitis involving small vessels
cause unknown. Can be seen in viral infections
114
Oral herpes =
Squamous cell ca =
HSV 1
tobacco and alcohol is major risk factors
floor of mouth most common location
oral leukoplakia and erythroplakia are precursor lesions
115
Salivary gland lesions
Mumps=
Sialadenitis =
Pleomorphic adenoma=
warthin tumour =
mucoepidermoid carcinoma =
mumps virus - bilateral inflammed parotid glands
orchitis, pancreatiis and aseptic meningitis may also be present
inflammation of the salivary gland. due to obstructing stone leading to staph aureus infection usuallu unilateral
benign tumour composed of stromal and epithelial tissue - MOST common tumour of the salivary gland
Arises in parotid - mobile, painless, circumscribed mass at the angle of the jaw. high rate of recurence
rarely transforms into ca
benign cystic tumour with abundant lymphocytes and germinal centres (lymph node like stroma) 2nd most COMMON tumour of salivary glands almost always in parotid
Malignant tumour composed of mucinous and squamous cells; most common MALIGNANT tumour of the salivary gland. arises in parotid and commonly involves the facial nerve
116
Two types of chronic gastritis =
Chronic autoimmune gastritis - autoimmune destruction of gastric parietal cells which are located in the stomach BODY and FUNDUS.
Associated with antibodies against parietal cells and/or intrinsic factor.
H.pylori gastritis - MOST COMMON FORM (90%) H.pylori induced acute and chronic inflammation.
most common in the ANTRUM
117
Peptic ulcer disease =
solitary mucosal ulcer involving the proximal duodenum (90) and distal stomach (10%)
Duodenal ulcer is almost always due to H. pylori. rarely may be due to ZE syndrome
biopsy shows hypertrophy of BRUNNER glands. Pain improves with meals
Gastric ulcer is usually due to H. pylori (75%) other causes - NSAIDS and bile reflux. Pain worsens with meals
ulcers usually at lesser curve of antrum.
Duodenal ulcers are almost never malignant
Gastric ulcers can be caused by gastric carcinoma
benign = < 3 cm sharply demarcated surrounded by radiating folds
malignant = larger, irregular with heaped margins
118
Gastric carcinoma
subtypes
- intestinal
- diffuse
malignant proliferation of surface epithelial cells
Intestinal type(more common) presents as a large, irregular ulcer with heaped up margins; most commonly involves the lesser curve of the antrum.
Periumbilical region (sister mary Joseph)
Diffuse type characterised by signet ring cells that diffusely infiltrate the gastric wall.
spread can involve left supraclavicular (Virchows node)
Distant mets most commonly to liver.
Krukenberg tumour
119
lactose intolerance =
celiac disease =
Tropical sprue =
Decreased function of the lactase enzyme found in the brush border of enterocytes
immune -mediated damage of small bowel villi due to gluten exposure; associated with HLA-DQ2 and DQ8
damage to small bowel villi due to unknown organism resulting in malabsorption.
Similar to coeliacs but occurs in tropical regions
120
Whipple disease =
Abetalipoproteinemia =
Carcinoid tumor =
Carcinoid syndrome =
Carcinoid heart disease = ?`
Systematic tissue damage characterised by macrophages loaded with tropheryma whippelii organisms. Classic site of involvement is the small bowel lamina propria.
Autosomal recessive deficiency of apolipoprotein B-48 and B-100.
Malignant proliferation of neuroendocrine cells, low-grade malignancy
positive for chromagrannin
Can arise anywhere along the gut - small bowel is most common site'
Often secretes serotonin. Serotonin is released into the portal circulation and metablosed by the liver into 5-HIAA
Mets of carcinoid to the liver allows serotonin to bypass the liver metablism
Serotonin is released into hepatic veins and leaks into systemic circulation via hepato-systemic shunts, resulting in carcinoid syndrome and carcinoid heart disease.
Characterised by bronchospasm, diarrhea and flushing skin; symptoms can be triggered by alcohol or emotional stress
Charactersied by right sided valvular fibrosis leading to tricuspid regurg and pulmonary valve stenosis
LEFT sided lesions are NOT seen because of MONOAMINE OXIDASE (metabolises serotonin) in the lung.
121
Hirschsprungs disease =
Defective relaxation and peristalsis of rectum and distal sigmoid colon - assoc with Downs syndrome.
Due to congenital failure of ganglion cells to descend into myenteric and submucosal plexus.
RECTAL suction biopsy reveals lack of ganglion cells.
122
Colonic Polyps - raised protrusions of colonic mucosa
Hyperplastic polyps = ?
Adenomatous polyp = ?
hyperplasia of the glands - MOST COMMON
left colon (rectosigmoid). Benign with no maligant potential
Neoplastic proliferation of glands- 2nd most common type of colonic polyp.
Benign but pre- malignant - may progress to adenocarcinoma via the adenoma-carcinoma sequence
123
Adenoma-carcinoma sequence =
molecular progression from normal colonic mucosa to adenomatous polyp to carcinoma
APC mutations increase risk for formation of polyp
K-ras mutation leads to formation of polyp
p53 mutation and increased expression of COX allow for progression to carcinoma; aspirin impedes progression from adenoma to carcinoma
124
FAP =
Gardner syndrome =
Turcot syndrome =
Autosomal dominant disorder charactersied by 100s to 1000s of adenomatous polyps
Due to inhereted APC mutation (chromosome 5)
FAP with fibromatosis and osteomas
FAT with CNS tumors
125
Juvenile polyp =
sporadic hamartomatous (benign) polyp that arises in children (<5yrs)
usually solitary rectal polyp that prolapses and bleeds
Juvenile polyposis = multiple juvenile polyps in stomach and colon. large numbers increase risk of ca
126
Peutz Jeghers syndrome
Hamartomatous (benign) polyps throughout the GI tract and mucocutaneous hyperpigmentation on lips, oral mucosa and genital skin
Increased risk for colorectla, breast and gynaecological cancer.
127
Colorectal carcinoma
pathaways ? =
HNPCC is due to ?
COLONIC carcinoma is associated with increased risk of what infection ?
What marker is used for assessing treatment response and detecting recurrence (nor for screening)
Carcinoma arising from colonic or rectal mucosa
most commonly from
adenoma-carcinoma sequence
Microsatelite instability
inherited mutation in DNA mismatch repair gene (microsatellite instability).
increased risk for colorectal, ovarian and endometrial cancer. arises de novo (not from adenomatous polyp) at early age and usually right sided
Strep Bovis endocarditis
CEA
128
Pancreatic ca
tumour marker?
Adenocarcinoma arising from the pancreatic ducts.
risk factor = smoking and chronic pancreatitis.
Ca19-9
129
gallstones - cholesterol or billirubin
MOST common is cholesterol stones
usually radiolucent
bilirubin stones - usually radiopaque
risk factors?
extravascular haemolysis
biliary tract infections -
Ascaris lumbricoides - round worm
Clonorchis senesis
130
Jaundice - causes?
RBCs are consumed by macrophages
Protoporphyrin (from heme) is converted to unconjugated bilirubin (UCB)
Albumin carries UBC to liver
uridine glucuronyl transferase (UGT) in hepatocytes conjugates bilirubin
Extravascular haemolysis or ineffective erythropoesis (high levels of UCB overwhelms liver)
Physiologic in the newborn (low UGT activity)
Gilbert syndrome - low UGT activity
Crigler-Najjar syndrome - absence of UGT
Dubin-Johnson syndrome -
Biliary tract obstruction
Viral hepatitis
131
Types of hepatitis ?
Hep A and Hep E - fecal oral. A = travelers, E - contaminated water or undercooked seafood. Only acute - no chronic
Hep B - parenteral transmission - acute or chronic
Hep C - parentral transmision - acute and chronic
Hep D -
132
What is the 1st serologic marker to rise in acute hepatitis?
What marker shows immunization ?
HBsAg - if present >6 months = chronic state
HBsAB
133
Viral hepatitis -
inflammation of liver parenchyma due to hepatitis virus
other causes - EBV and CMV
134
Cirrhosis -
End stage liver damage - disruption of normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes. Mediated by TGF-B from stellate cells
135
Haemachromatosis
excess body iron leading to deposition in tissues and organ damage due to free radicals
Due to autosomal recessive defect in iron absorption (primary) or chronic transfusions (secondary).
136
primary haemochromatosis =
due to mutation in HFE gene usually C282Y
increased risk of HCC
137
Wilsons disease =
Autosomal recessive defect in (ATP7B gene) in ATP mediated hepatocytes copper transport
Kayser Fleisher rings in the cornea
increased risk of HCC
138
Primary biliary cirrhosis =
Primary sclerosing cholangitis =
autoimmune granulomatous destruction of intrahepatic bile ducts
inflammations and fibrosis of intrahepatic and extrahepatic bile ducts
periductal fibrosis with onion skin appearance
cause unknown but assoc with UC and P-ANCA +
increased risk of cholangiocarcinoma
139
Reye syndrome -
Liver failure and encephalopathy in children with viral illness who take aspirin
140
Hepatic adenoma
benign tumor of hepatocytes
assoc with OCP - regress if stopped
risk of rupture and intraperitoneal bleeding esp during pregnancy
tumours are subcapsular and grow with exposure to estrogen
141
HCC
serum marker?
Malignant tumour of hepatocytes
Risk factors - HBV and HCV
Cirrhosis
Alfatoxins derived from aspergillus
increased risk for Budd-Chiari syndrome
AFP
142
Normocytic anaemia with predominant intravascular haemolysis?
1- Paroxysmal nocturnal haemaglobinuria
2- G6PD deficiency
3- immune haemolytic anaemia
4- microangiopathic harmolytic anaemia
5- malaria
