Week 2: Pathological Mechanisms Flashcards
Define cell, tissue, organ and system; and describe the body’s organ systems & constituent organs and function
Cell: smallest, functional unit of an organism
Tissue: group of cells that perform the same function e.g. epithelial (squamous, glandular), connective (blood vessels, fat, muscle, bone), haemato-lymphoid
Organ: different tissues which together perform specific function e.g. cardiovascular, respiratory
Define pathology and disease; and list and define the broad categories of disease
Pathology: Study of disease Pathology can be divided into general and systemic. General: processes occurring in general e.g. inflammation Systemic: processes occurring in a system e.g. cardiovascular Disease: Abnormality of cell/tissue structure and/or function due to causative agent and body’s response to it Broad categories of disease: VITAMIN CDEF: Vascular, Infective/ Inflammatory, Traumatic, Autoimmune, Metabolic, Iatrogenic/ Idiopathic, Neoplastic, Congenital, Degenerative/ Developmental, Endocrine/ Environmental and Functional Possible causes of disease (Congenital versus acquired) Physical agents (mechanical, heat, radiation (DNA damage)) Chemicals/drugs: damages organelles and processes e.g. plasma membrane, protein folding Infections Hypoxia/ischaemia: Hypoxia (lack of O2). Disrupts oxidative respiration in MT, decreases ATP. Ischaemia (reduced blood supply inc. nutrients and O2) to tissue. Damage more rapid and severe Immunological reactions: Anaphylaxis, Auto-immune reactions Nutritional Endocrine/ metabolic Genetic disease
State that disease can be described in terms of epidemiology, aetiology (cause), pathogenesis(mechanism) and sequelae (consequences) and explain these terms with examples
Epidemiology: incidence, distribution, and control of disease in a population
Describe what is meant by reversible and non-reversible cell injury
Reversible cell injury: Changes due to stress in environment. Return to normal once stimulus removed
Irreversible cell injury: Permanent, necrosis usually occurs
There is a threshold between reversible and irreversible
Reversible: - Cloudy swelling: osmotic disturbance, loss of ATP dependent Na pump causes Na influx, build up of metabolites
- Cytoplasmic blebs: swollen MT
- Fatty change: accumulation of lipid vacuoles in cytoplasm due to disruption of fatty acid metabolism
Irreversible:
- Disrupted membranes, Pyknotic nucleus (chromatin shrinks in nucleus), Karyorrhexis (fragmentation of nucelus)
Give clear definitions of necrosis and apoptosis and describe the circumstances in which they arise
Necrosis: Unprogrammed cell death
- cell death after injury usually necrosis
always pathological - release cell contents (cell lysis) causing damage and inflammation
- cell swelling
- disruption of plasma membrane and organelles
- DNA disruption
Apoptosis: Programmed cell death
- usually physiological
- can be pathological e.g. viral infection, hypoxia
- cell shrinkage, chromatin condensation, membranes of cell and MT intact, cytoplasmic blebs form into apoptotic bodies which are phagocytosed
- doesn’t cause inflammation
Types of necrosis
Coagulative: firm, tissue outline retained e.g. haemorrhage, gangrene
Colliquitive: tissue becomes liquid and structure lost e.g. abcess, cerebral infarct
Caseous: combination of coagulative and colliquitive
Looks “cheese like.” Classic for granulotamous inflammation e.g. TB
Fat: due to lipases on fatty tissue
Outline the nature, causes and effects of amyloid
Amylois is a general pattern/appearence due to multiple proteins and causes e.g. cirrhosis
Accumulation can be systemic or localised
Due to:
- Accumulation of a normal protein (systemic deposition) - AL amyloid (too many antibody light chains produced, produced in B cell neoplasms e.g. multiple myeloma),
AA myloid (amyloid associated protein produced in liver. Produced in chronic inflammation e.g. RA
- Production of an abnormal protein - folding of soluble protein fibrils into abnormal, insoluble aggregates e.g. Alzheimer’s Amyloid important in systemic pathology especially in kidney, osteo-articular system and brain
Outline the nature, causes and effects of pathological pigmentation (deposition)
Deposition of lipid causing steatosis in liver
Lipofuscin - wear and tear, or age pigment in liver. Endogenous breakdown product. Can deposit in heart and other organs.
Iron- excess iron in liver. Can be genetic cause- haemochromotosis
Carbon - lines lung serosal surface, lymphatics. Due to breathing in air.
Calcification
Deposition of calcium salts Can be:
Dystrophic: Deposition in abnormal tissue with normal serum Ca2+ e.g. in caeseous necrosis in TB
Metastatic: Deposition in normal tissue but increased serum Ca+. Usually in connective tissue e.g. blood vessels, valves
Causes:
Increased PTH due to primary (pituitary tumour) or secondary (kidney disease)
Describe inflammation and its role in pathology/physiology
Response to tissue damage. Function is to stop harmful stimulus, initiate repair and restore function. Can be acute or chronic
Beneficial - dilutes toxins in oedema fluid, increased entry of drugs and antibodies
Not beneficial - digestion of normal tissue, swelling, inappropriate response e.g. hypersensitivity
Explain how changes in the vasculature and cells (neutrophils, macrophages and mast cells) occur and how they contribute to clinical signs
Vascular dilatation
- Histamine, NO
- Arterioles dilate, stasis of blood, fluid passes into tissue
Neutrophil activation
- Chemotaxis, margination, rolling, adhesion, migration pass between endothelial cells
- Phagocytosis
Endothelial activation
- Bradykinin, 5-HT
- Activates vascular endothelium
- Increased leakiness of endothelium
- Plasma proteins pass into tissue e.g. immunoglobulins
Clinical signs - red (due to hyperaemia), heat (due to hyperaemia), oedema (due to fluid exudate), pain (release of bradykinin and PGE2), loss of function (combination of everything)
Describe various types of exudates
(Exudate - fluid leaking from blood vessel)
Neutrophilic exudate - suppurative/purulent - aggregration of pus
Fibrinous exudate
Serous exudate
Describe the main concepts of how infection may spread
Localised infection:
- Remain at initial site
- Spread to local lymph nodes via draining lymphatics
Systemic infection: - Haematogenous – i.e. spread through blood/lymph to cause SYSTEMIC INFLAMMATORY RESPONSE
Outline, with examples, how various chemical mediators affect the inflammatory response
Histamine, NO involved in vascular activation
Leukotrienes involved in neutrophil activation
Bradykinin, 5-HT, histamine involved in endothelial activation
Describe how the inflammatory response is controlled (at a basic level) including various possible sequelae
Acute inflammation can cause formation of abscess (collection of neutrophil polymorphs).
Can resolve by itself, heal by repair (usually involves fibrosis) or become chronic inflammation
Define chronic inflammation and described the circumstances in which it arises
Persisting tissue damage and ongoing acute inflammation
Involves chronic inflammatory cell infiltrate: lymphocytes, macrophages and plasma cells
Often leads to fibrosis or scarring
Granulomatous inflammation (aggregrates of macrophages) a sub-type of chronic inflammation
Outline what is meant by granulomatous inflammation
Subtype of chronic inflammation
Defined by the presence of granulomas, collections of epithelioid macrophages and multinucleate giant cells
- Formation of granulomas is due to T cell mediated immune reaction (Delayed Hypersensitivity Reaction)
- The antigen is presented to CD4+ T Cells which produces IFN gamma and other cytokines resulting in macrophage activation (become epithelioid macrophages)
Outline histopathological features of chronic inflammation and give examples of diseases with a chronic inflammatory basis
Infiltration of plasma cells, eosonophils and macrophages
Also accompanied by fibrosis, tissue destruction
Granulomatous inflammation is subtype of chronic inflammation
Diseases with chornic inflammatory basis: Pulmonary fibrosis, Cirrhosis
Define healing and the different processes involved
Healing: restoration of structure and function of injured/diseased tissue
Resolution - restoring tissue to normal
Two mechanisms:
Regeneration - parenchymal cells divide and replenish lost tissue
Organisation - formation of scar
Describe process of organisation
When resolution or regeneration not possible, necrotic parenchymal cells replaced by collagen
- Involves formation of new blood vessels, and influx of fibroblasts occurs which lay down collagen
- Combination of new blood vessels, fibroblasts and granulation tissue
- When granulation tissue forms, chronic inflammation occurs
- Occurs in endothelial cells
Describe the various stages in healing of a wound including skin/mucosa and fractures
Skin healing occurs via:
Primary intention: if there is limited tissue damage e.g. simple incision. Wound edges bought together - minimal scar formation
Secondary intention: lots of tissue damage e.g. infected wound. Wound edges not bought in together, granulation tissue fills in defect, and causes contraction of wound, making it smaller and scar formed
A granulomatous reaction includes foreign body multinucleate giant cells. These partly surround the suture material and secrete proteolytic enzymes in an attempt to digest it.
Mucosa heals by regeneration.
Underlying tissue heals by organisation.
Bone heals by regeneration (not repair), and callus formation
Discuss factors which may interfere with wound healing
- Infection
- Poor diet (lack of protein)
- Poor blood supply
- Glucocorticoids (delays collagen formation)
- Moisture (promotes bacteria growth)
- Neutrophil disorder
Describe and explain the division of the immune system into innate and adaptive.
Innate: Non-specific defense. Includes physical barrier - skin, chemical barriers, macrophages, dendritic cells. Innate can activate adaptive immunity if required.
Adaptive: Antigen-specific defense. Antigen recognised, processed and lymphocytes (T and B cells) produced which specifically attack pathogen. Has “memory” which makes killing pathogen next time more efficient.
Further describe and explain the division of the adaptive immune system into humoral and cellular components and their interdependence
Understand the functional divisions of lymphocytes into B and T cells, and their subdivisions
Humoral: Kills extracellular pathogens e.g. bacteria
- Antibodies: opsionise for phagocytosis, activate complement, neutralise toxins
- Memory B cells
Antibodies:
IgM (pentameric) - main antibody of primary immune response, low affinity, activate complement
IgG (monomeric) - main antibody of secondary immune response, high affinity
IgA (dimeric) - “antiseptic” paint. Present in secretions and lines epithelial surfaces. Blocks pathogen binding. Important in nose, lung, gut as on mucosal surfaces
IgE (monomeric) - higher affinity to mast cells. Role in allergy. Parasite infection.
T helper cells activate B cells to:
- become antibody secreting plasma cells
- undergo isotype switching to IgG, IgA, IgE (as IgM at start) - affinity maturation
- become memory B cells
Cellular: CD4 (helper) T cells
- activates B cells, CD8 T cells CD8 (killer) T cells
- kills intracellular pathogens e.g. viruses
T cell receptor recognises only antigen when presented within a MHC molecule on its surface. Recognises short peptide lengths.
MHC I:
Presents to CD8 T cell
On all nucleated cells
Presents intra-cellular antigen
MHC II:
Presents to CD4 T cells
Presents extra-cellular derived (phagocytosed) antigens
Found on APCs (dendritic, macrophages, B cells)
List and describe the function of the main molecular components of the immune system including cellular and circulating factors: these include soluble factors, cellular factors, and other immune cell receptors, the major histocompatibility complexes, complement and other circulating factors including cytokines and chemokines
Innate:
- Soluble factors: Antibacterial factors, Complement system
- Cellular factors: Scavenger phagocytes
Antibacterial: lysosome (breaks down gram positive bacterial cell wall), lactoferrin (protein on mucosal surface which chelates iron, inhibits bacterial growth)
Complement: Classical (antigen:antibody complexes), MB-lectin (lectin binding to pathogen), alternative (binding directly to pathogen) causes recruitment inflammatory cells, opsionisation, killing pathogens.
Scavenger phagocytes (inc. macrophages, dendritic cells, neutrophils): Macrophages can present antigen to T cells in MHCII in lymph node.
Produce cytokines e.g. M1 to recruit neutrophils
Cytokines are proteins/signalling molecules produced by many cells (B cells, T cells, endothelial cells) in response to an immune stimulus.
Involved in cellular communication
Chemokines -type of cytokine, induces chemotaxis (cell migration in response to a chemical)
Describe the structure and function of cells of the immune system such as neutrophils, macrophages and lymphocytes.
Neutrophils: 50-70% WBCs.
- Migrates to bacterial products in response to chemokines
- Ingest/destroy pathogens by secreting proteases, lysosomes
- Release toxic granules extracellularly
- Dies locally: forming pus
Eosinophils
- Responds to parasites
- Pathogloical role in allergy
- Migrate in response to chemokines e.g. eotaxin
- Kills parasites by degranulation - releases toxic substances
- Produces cytokines which drives inflammation e.g. IL-1, 2, TNF-a
Basophils (blood), Mast cells (tissues):
- Mast cells “guards” mucosal surfaces
- Involved in allergy
- Releases pre-formed granules contain cytokines, histamine - wheal and flare reaction
- Cytokine release: stores pre-formed cytokines which are released to drive inflammatory response
Dendritic cells: Links between innate and adaptive immunity APC
- derived from same precursor as macrophage
- phagocytoses pathogens, migrates to lymph node, presents antigen to CD4 T cells, initiate adaptive immunity
Prevention of autoimmunity
B cells - Develops in bone marrow
- If B cell binds strongly to “self” antigen in bone marrow, it will apoptose
T cells - Develops in bone marrow, matures in thymus
- If T cell receptor binds to “self” antigen in thymus, apoptoses.
- Activation of both cell types require “second signals”.
- If bind without second signal, becomes anergic (no reaction by immune system) e.g. T cells must express CD3 and CD4/CD8 and bind to MHC
Describe the structure and function of these organs and cells, including lymph nodes and spleen
Primary organs of adaptive immune system:
- Bone marrow
- Thymus
Secondary
- Lymph nodes
- Spleen (filters blood of blood borne pathogens and senescent cells)
- Mucosal associated lymphoid tissue (MALT) e.g. in GI tract
Primary and Secondary B cell response
Primary response:
- Naive B cells becomes activated.
- IgM>IgG.
- Antibody affinity is low
Secondary response:
- Memory B cells allows immediate plasma cell proliferation and antibody production.
- Antibody affinity is high (lower threshold for activation) and patrol sites of previous pathogen entry
- Isotype switching: increase in IgG and if needed IgA and IgE
Steps of what happens during infection
- Neutrophils arrive at site of infection and phagocytose
- Dendritic cells phagocytose (recognises PAMP on pathogens) and carry antigen, leave via lymphatics
- Naive T helper cells enters lymph node from HEV (high endothelial venule) and binds to DC via TCR (requires seocnd signal and MHCII)
- Once naive T cell activated, differentiate into CD4 T cells
- CD4 T cells activates B cells (by identifying the correct antigen in their MHC II) and providing a second signal. CD4 T cells also release cytokines to promote B cell development
- Activated APCs present antigen within an MHC I to CD8 T cell (second signal needed. CD4 cells secrete cytokines to activate CD8 cells)
- Activated B cells become antibody secreting plasma cells
- B cell enters lymphoid follicle to form germinal centre and undergo affinity maturation (ones with highest affinity, encouraged to proliferate)
- B cells with highest affinity selected to become memory B cells
Type I hypersensitivity
- Response to challenge occurs immediately
- Increase severity upon repeated challenge
- Mediated by IgE on mast cells
- Involved in most allergies, asthma, eczema
Severe, systemic type I hypersensitivity: Anaphylaxis - Widespread degranulation due to systemic exposure to antigen
- Increased vascular permeability leading to soft tissue swelling which threatens the airway, loss of circulatory volume causing shock
1. Sensitisation
2. Mast cells primed with IgE
3. Re-exposed to antigen
4. Antigen binds to IgE on mast cells
5. Mast cells degranulate, releasing pro-inflammtory cytokines, histamine
6. Pro-inflammatory process stimulates future repsonses
Type II hypersensitivity
- Due to antibodies binding to antigen on own human cells
- IgG usual cause
- Drug associated haemolysis
- Common cause of autoimmune diseaese e.g. pernicious anaemia, myasthenia gravis, autoimmune haemolytic anaemia, bullous pemphigoid
1. Sensitisation
2. Opsionisation of cells
3. Cytoxicity occurs - complement activation - destruction of tissue
Type V hypersensitivty: When antibodies bind to receptors on cell
Type III hypersensitivity
- Immune complexes (soluble antigens bind to antibodies (IgM or IgG)
- Cause of auto immune disease and drug allergy
- Can aggregate in blood vessel causing occlusion, complement activation, perivascular activation
E.g. hypersensitivity pneumonitis, SLE
Type IV hypersensitivity
Delayed type hypersensitivity - e.g. contact dermatitis
- Presents days after exposure
- Mediated by T cells (CD4 and CD8) infiltrating area
Autoimmune disease
Harmful inflammatory response directed against ‘self’ tissue by the adaptive immune response
Can be:
- Organ specific (TMD1, myasthenia gravis)
- Systemic (RA, IBD)
Pathogenesis:
Genetic predisposition e.g. MHC I and II
Environmental factors e.g. infection (molecular mimicry occurs - where foreign and self antigen are similar causing cross reactivity), geographical factors e.g. vit D levels
Coagulative necrosis
Firm, tissue outline retained e.g. haemorrhage, gangrene
Colliquitive necrosis
Tissue becomes liquid and structure lost e.g. abcess, cerebral infarct
Caseous necrosis
Combination of coagulative and colliquitive. Looks “cheese like.” Classic for granulotamous inflammation e.g. TB
Fat necrosis
Due to lipases on fatty tissue
What are depositions?
Abnormal accumulation of substances
Can be composed of:
Endogenous:
- Normal products of metabolism
Intracellular: melanin, haemosiderin
Extracellular: amyloid
Exogenous:
Intracellular and extracellular: tattoo pigments, asbestos
Antibody structure and function
Fab region - antigen binding region
Fc region - binds to Fc receptors on phagocytes. Activates complement
Function:
Opsionise pathogens
Activates complement
Neutralise toxins
Myasthenia Gravis
Syndrome of fatiguable muscle weakness
Affects limbs, head and neck
Due to IgG against AchR. Blocks signal transuction.
RA
Multisystem autoimmune disease
Skin inflammation, small vessel vasculitis, valvular inflammation
Rhematoid factor (auto-antibody) against Fc region of IgG. Forms large immune complexes.
Anti-citrullinated antibodies common (due to conversion of alanine to citrulline)
- Activation of inflammatory cascade leads to release of cytokines (e.g. TNF) which attacts macrophages, neutrophils to synovium
- Leads to osteoclast activation, joint destruction, systemic inflammation
Treatments
Biologics: Infliximab (Anti-TNF) - reduces joint swelling, systemic inflammation
However increases risk of infection esp. TB
Normal haemostasis
Vessel injury leads to vasoconstruction, platelet release and activation of coagulation cascade
Platelets aggregrate and adhere to vascular subenothelium via von Willebrand factor, forming primary haemostatic plug
Primary haemostatic plug forms a stable haemostatic plug due to cross-linking of fibrin (produced by thrombin via coagulation cascade)
Virchow’s triad
3 things that contribute to thrombosis:
- Hypercoaguable state e.g. malignancy
- Vessel wall injury e.g. trauma
- Stasis of blood flow e.g. AF
Histopathology of thromosis
Aterial:
- White thrombus
- Many platelets, small amounts of fibirin
Venous:
- Red thrombus
- Many fibirin with trapped RBCs
Differential diagnosis of sore leg
Trauma
Non-traumatic e.g OA, RA
Skin infections e.g. Cellulitis, Nec fas
Venous occlusion e.g. DVT
Bilateral leg swelling e.g. heart failure, cirrhosis, malnutrition
Deep vein thrombosis
- Thrombosis in deep venous system, usually in legs
Clinical features:
- Pain, swelling in one leg, red skin
- Usually superficial femoral vein
- 50% DVT cases will have PE
Risk factors:
Vessel wall: age, surgery
Blood flow: obesity, immobilisation
Composition of blood: thrombophilias, inflammatory conditions
Investigations:
Blood tests: Fibrin D-dimer (fibrin degradation product)
Well’s Clinical Scoring system (<2 DVT possible)
Imaging: US
Treatment:
- Anticoagulation: LMWH, warfarin, DOACs e.g Apixiban (Xa inhibitor), Dabigatran (IIa (thrombin) inhibitor)
Remove risk factors
Compression (anti-embolism) stockings
Necrotising granuloma
Collection of epithelioid macrophages with necrosis in centre
– related to TB
Non-necrotising granuloma
No necrosis in centre (centre of pink aggregrates - macrophages)
- Sarcoidosis, Chron’s
Causes of chest pain
Cardiac:
Angina, MI
Respiratory:
Pleuritic chest pain - infection (pneumonia)
Vascular:
- PE
GI:
- Acid reflux, hiatus hernia
MSK:
- Rib fracture
PE
Due to thrombus formation in deep vein in body, usually from lower leg (DVT), which travels and blocks blood vessel in lung
Symptoms: dyspnoea, chest pain, haemoptysis
Leads to:
- Lung collapse
- Recurrent VTE (venous thromboembolism)
- Thromboembolic pulmonary hypertension
Management:
O2
Anti-coagulation e.g. heparin, fondaparineux, warfarin
Thrombolysis e.g. alteplase or catheter directed thrombectomy
Coronary artery disease
Atheromatous arterio-vascular disease
- Development of plaques in arteries (due to athersclerosis - build up of plaque due to accumulation of cholesterol)
- Leads to progressive narrowing and stenosis of artery
- Leads to plaque rupture, formation of an acute thrombus, vascular occlusion, ischaemia (reduced blood supply to organ) and infarction (tissue has become necrotic due to reduced blood supply)
Arteriosclerotic cardiovascular disease
Arterial wall thickens due to accumulation of cholesterol and triglycerides
Risk factors:
- Hypetension, smoking, hyperlipidaemia, diabetes
Diagnosis of MI
- History
- Evidence of cardiac dysfunction
- ECG findings
- Biochemical evidence of ischaemia (elevated troponin)
- visualisation of coronary arteries
Treatment:
- Anti-platelet agents: aspirin
- Anti-coagulant agents: heparin
- Thrombolytic drugs: tenecteplase, PCI
- Widen plaque: balloon angioplasty
- Prevent furthur thrombus: anti-platelets, statin
Complications:
- Arrhythmia, HF, pericarditis, death
Causes of limb weakness
MSK:
- Myopathy
- Arthropathy (disease of joint)
Neurological:
- Peripheral neuropathy
- Spinal lesion
- Cerebral lesion
Common presentations of thrombosis or thromboembolism
Sore leg - DVT
Chest pain - Coronary artery disease
Limb weakness - Stroke
Treatment of stroke
Thromolysis
Remove source of thrombus - Anticoagulation, Cardioversion - revert to sinus rhythm, replace defective heart valve
Address other cardiovascular disease risk factors:
- Hypertension, hyperlipidaemia
What does cellular pathology involve?
Autopsy (post mortem examination), histopathology (tissues) and cytopathology (cells)
Describe typical specimens received in a pathology lab, and their range in size from cytology through biopsies to larger resection specimens
Cytology samples :
- Fluid cytology
- Smear
- Fine needle aspirate
Small tissue biopsies:
- punch biopsies (skin), excision biopsy
Larger tissue resections
- hysterectomy
Describe how specimens are handled in pathology laboratories, from gross examination through tissue processing to microscopy and reporting, and likely timescales involved
- Tissue removed during surgery
- Put into formalin
- Transported to pathology lab
- Specimen examined
- Tissue processed: dehydrated with alcohol, cleared with Xylene in preparation for wax
- Tissue embedded in wax
- Tissue stained by HandE
- Tissue examined by pathologist
Urgent: <1 wk
Other: < 4wks
Describe common techniques used in pathology, including immunohistochemistry (IHC) and molecular pathology, and briefly explain their applications
H&E is standard
Special stains used to identify certain features e.g. despositions - (amyloid, iron) infections -
IHC:
- brown staining
- tumour diagnosis and classification
Molecular pathology:
- Studies DNA, RNA, protein
- Large scale qualitative changes in DNA e.g. FISH to detect changes in DNA e.g. chromosomal translocation, tumour classification
- Large scale quantitaive changes in DNA e.g. PCR - tumour classification
- Small scale chanes in DNA e.g. next gen sequencing
Describe common congenital and developmental abnormalities of growth including hamartomas and ectopias
Congenital abnormality: anomalies at or before birth
2 types:
Functional: how the body works e.g. CF
Structural: how it’s physically made up
Development abnormality: deformity when growth is disturbed
Developmental abnormality = congenital structral abnormality
Harmatoma
“Harmation” = bodily defect
- Malformation that resembles a neoplasm due to faulty growth in organ
- Composed of mixture of mature tissue elements normally found at that site
Chondroid harmatoma: Lung leision (can look like coin leision on X ray). Composed of epithelium, cartilage, fat. Benign.
Ectopia
“Ektopas” = out of place
Abnormal location of tissue or organ, can be congenital or due to injury
Ectopic cordis: dispalcement of heart outside body
Ectopic pregnancy: implantation occuring in fallopian tube, not in endometrium
Define hypertrophy and hyperplasia, atrophy, and metaplasia; give an account of important physiological and pathological factors and stimuli responsible for these changes and illustrate each of these processes with specific examples
Relate these processes to altered tissue homeostasis including cell proliferation
Hypertrophy: increase in size of cells
Physiolgical causes: exercise
Physiological causes: cardiac disease
Hyperplasia: increase in no. of cells
Physiolgical causes: hormonal (proliferative endometrium)
Pathological: excess hormones e..g obesity, BPH
Atrophy: decreased size/no. of cells
Physiological: menopause
Pathological: decreased blood supply - vascular dementia
Metaplasia: reversible change of one differentiated cell type into another. (So cells are better adapted to withstand environment)
Physiogical: in people with gastric reflux, stratified squamous of oesophagus are replaced by gastric columnar
Pathological: Can lead to dysplasia - carcinomas
Homeostasis: normal cells in a steady state. Injury can induce changed in homeostasis which leads to cell adaption or cell death
Adaptions are reversible changes in no./size of cells in repsonse to changes in environment.
Can be physiological (response of cells to stimulation) normal or pathological (repsonse of cells to stress, allowing cells to avoid injury)
Discuss the effects of mechanical tissue injury including diverticula, intussusception and herniation.
Diverticula - small bulges that develop in the lining of intestine
Diverticular disease: small bulges herniate/protrude through bowel wall
Merkel’s diverticulum
- Congenital
- Usually at terminal ileum
- Remanant of yolk sac has failed to involute
- Contains all layers of intestine, and ectopic tissue (pancreatic)
- Complications: inflammation, bleeding, perforation
- Can mimic appendictis due to location
Intussusception - part of the intestine into the section next to it. Usually small intestine. Usually in children.
Herniation - abnormal protrusion of organ through a defect or opening in a membrane
Ventricular septal defect
Hole in the ventricular septum (wall dividing left and right ventricles)
Assoc. with Down’s syndrome
Can lead to increase in pulmonary resistance and eventually cyanosis
Spinal bifida
Defect in neural tube (develops into SC and brain) where it fails to close
Symptoms: muscle weakness, bowel/bladder problems
Offer a definition of a neoplasm, and critically discuss that definition
Abnormal tissue growth, which is excessive (not physiological) and uncoordinated compared to adjacent normal tissue. Persists even after stimuli that cause it has stopped
Excessive growth can be:
- neoplastic (benign or malignant) (uncontrolled, non reversible)
- non neoplastic (controlled, reversible)
However. tumours and neoplasms are different
Tumour = swelling/lump
Not all swellings are tumours e.g. harmatomas
Not all neoplasms cause swelling e.g. leukaemia
Define dysplasia and its synonyms, and its significance for carcinogenesis
Dysplasia - disordered cell growth where cells fail to differentiate properly, but contained by basement memnbrane
Alterations in appearence of cell - cell nuclei more hyperchromatic, nuclear to cytoplasmic ratio increases
Can regress, persist or progress
Differences between benign and malignant neoplasms, and show how some tumours do not fall neatly into either category
Benign : neoplasm that doesn’t invade adjacent tissue, usually well circumscribed
- Usually ends with -oma
- Adenoma (glandular tissue)
- Leioma (smooth muscle)
Malignant: neoplasm invades surrounding tissue, can metastasise
- Carcinoma (epithelial (cells in skin/lining of organs) origin)
- Carcnioma in situ (epithelial dysplasia, not beyond BM). No risk of metastasis as no blood vessels or lymphatics in epithelium above BM.
- Sarcoma (mesenchymal (connective or non-epithelial tissue) origin)
- Melanoma
- Lymphoma
- Germ cell tumours
- Lymphoma
Describe the different routes of tumour growth and spread
Local invasion - growth into surrounding tissue by expansion
- Benign tumours never locally invade
- Malignant tumours always locally invade
- Can occupy space, locally destructive, uclerate, invade nerves - pain
E.g. oeosophagus - difficulty in swallowing, head of pancreas - jaundice
Metastatic - spread of tumour to distant sites
Lymphatic spread - typical of carcinomas
Haemotogenous spread - typical of sarcomas. Liver/lungs typically invovled.
Transcoloemic spread - malignant neoplasm spreads into a natural opening e.g. gastric carcinoma
Presentation of Mets:
Skin leisions, CNS symptoms, breatlessness, haematemesis, jaundice
Understand the principles of tumour grading and staging and its clinical relevance
Differentiation - extent to which tumour cell resemble normal cell
Range of differentiation - well, moderate, poor, undifferentiated (anaplasia)
Importance of differentiation:
- Prognosis (well differentiated better prognosis)
- As tumours becomes poorly differentiated, higher the grade
Stage
TNM staging
Tumour - size
Nodes - how many involved
Metastasis - if tumour has metastasised, then late/stage IV
Discuss the techniques by which a neoplastic diagnosis may be established
History, clinical examination
Imaging - XR, CT, MRI
Bloods - FBC, UandEs, LFTs, tumour markers e.g. Ca 125 (ovarian), Ca 19-9 (pancreas)
Cytology - pap smear, FNA
Biopsy - histolopathology
Molecular - gene detection
