Path revision Flashcards
Increase in the number of cells =
Hyperplasia
Increase in the size of cells =
hypertrophy
Cells that cant undergo hyperplasia - only hypertrophy
Cardiac muscle
Skeletal muscle
Nerve
Conditions that don’t have and increased risk of cancer despite hyperplasia =
Benigh prostatic hyperplasia
Apocrine metaplasia
Decrease in cell # occurs via
What changes occur in the cell during apoptosis
Apoptosis
decrease in size, red cytoplasm and condensed nucleus
Decrease in cell size occurs via
Ubiquiten proteosome degradation
Causes of metaplasia
Stress, Vitamin A deficiency,
Dysplasia
Disordered cell growth/proliferation of precancerous cells
Hallmark of reversible cell injury =
Hallmark of irreversible injury =
Hallmark of cell death =
cellular swelling
membrane damage
Loss of nucleus
Necrosis =
what changes are seen in the cell?
Apoptosis =
causes of apoptosis - 2
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
Types of necrosis (6)
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
Apoptosis is mediated by ?
and activated by multiple pathways ?`
Caspases
Intrinsic mitochondrial pathway
Extrinisc receptor - ligand pathway
Cytotoxic CD8 T cell mediated pathway
Free radicals cause damage via
Elimination is via
Peroxidation of lipids
Oxidation of DNA proteins
Antioxidants - glutathionine, Vit A, C and E
Amyloid =
Can be systemic or local
misfolded protein which deposits in the extracellular space
Beta pleated sheet configuration
Congo red stain and green apple birefringence
Primary amyloid =
Secondary amyloid =
AL amyloid - associated with MM derived from immunoglobulin light chain
AA amyloid - derived from serum amyloid protein
Inflammation -
Acute or chronic
Acute inflammation mediators?
Acute - Oedema and neutrophils
Chronic - Lymphocytes and plasma cells
Toll like receptors
Arachidonic acid metabolites
Mast cells
complement
Hageman Factor (F12)
Neutrophil arrival and function
Margination
Rolling
Adhesion
Transmigration and chemotaxis
Phagocytosis
Destruction of phagocytosed material
Resolution
Neutrophils are attracted by bacterial products - ?
IL-8
C5a
LTB4
Chronic granulomatous disease =
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
What test is done to screen for CGD?
Nitroblue tetrazolium
T lymphocytes
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
T lymphocytes
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
Granuloma =
Caseous granuloma
Non caseous granuloma
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
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
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
Autoimmune disorders (4)
SLE
Sjogrens
Scleroderma
Mixed connective tissue disease
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
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
Sjogrens syndrome
Autoimmune destruction of lacrimal and salivary glands
Lymphocyte mediated damage - Type IV HS with fibrosis
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)
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
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
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
Cutaneous healing occurs via?
Primary or secondary intention
Clonality of cells is determined by ?
Clonality of Blymphocytes is determined by
G6PD or
androgen receptor isoforms
Ig (light chains)
Most common adult ca by incidence?
Mortality?
incidence - 1 = brst/prostate
2 = lung 3 = colorectal
Mortality - 1 = lung 2 = brst/prostate 3 = colorectal
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.
Li Fraumeni syndrome
Germline mutation of P53
leads to multiple types of carcinomas and sarcomas
Sporadic mutation of RB =
Germline mutation of RB =
Unilateral retinoblastoma
Bilateral retinoblastoma and osteosarcoma
Bcl2 - normally stablisizes mitochondrial membrane blocking release of cytochrome C (activates apoptosis)
Bcl2 is over expressed in
FOLLICULAR LYMPHOMA
Lymphatic spread is characteristic of ?
Haematogenous spread is characteristic of ?
Carcinomas
Sarcomas and some carcinomas
- HCC
- RCC
- follicular ca of the thryoid
- choriocarcinoma
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.
vWF is derived from ?
Weibel palade bodies of endothelial cells and alpha granules of platelets
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
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
Other disorders of haemostasis
Heparin induced thrombocytopenia
DIC - pathologic activation of cascade
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)
Thrombus is characterised by ? (2)
Lines of Zahn
Attachment to vessel wall.
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)
Hypercoagulable state causes ?
Protein C or S deficiency
Factor V Leiden deficiency
Prothrombin 2010A
ATIII deficiency
OCP
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
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
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
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
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
Thalassemia =
Carriers are protected against?
Decreased synthesis of globin chains of Hb
Plasmodium falciparum malaria
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