Pathology
General Pathology
Abscess and Pus
Pus
Composed of two phases
1. Solid:
o
o
o
live/dead polymorphs, macrophages
Bacteria/causative agent (eg irritant chemicals)
Dead human cells
2. Fluid: contains exudate
o Immunoglobulins (for opsonisation - 1IgG, 2IgM)
o Complement - chemotaxis, anaphylaxis, opsonisation
o Clotting factors
o Inflammatory mediators
Abscess




Localised collection of pus
If loculated = pus, if free = empyema
Wall composed of granulation tissue "pyogenic membrane"
Natural history is to dischage through line of least resistance
1. enzymes released from polymorphs/macrophagtes break down long
chain molecules
2. increases osmotic pressure (as more molecules)
3. Swells pus collection
4. Discharges
Agenesis Aplasia Atrophy
Agenesis
Complete failure of organ to develop (at all)

Di George syndrome - failure of developement of third and fourth pharyngeal
pouches (leads to no thymus and parathyroid glands)
Aplasia
Failure to attain size or function - recognizable tissue that has failed to fully develop

Biliary atresia - failure to develop a lumen within the biliary tree!
Atrophy
Reduction in normal cell size or number. (Cf hypertrophy - increase in size,
hyperplasia - increase in number)


Physiological
1. Childhood: thymus, umbilical vessels
2. Adulthood: Menopausal uterus/vagina
Pathological
1. Starvation, ischaemia, disuse (immobilization
Amyloidosis
Amyloid



Family of extracellular proteins composed of B-pleated sheets
Mammalian systems have no enzyme to degrade these compounds (similar to
silk ligatures)
Have apple-green birefringnce on polarised light after staining with Congo red
Classification
AL
Amyloid Lymphocyte origin: Primary amyloid
Soluble precursor Ig light chains (esp from myeloma)
1. Heart: restrictive cardiomyopathy
2. Nerves: neuropathy
3. Skin: may result in carpal tunnel syndrome
AA
Secondary/Reactive
a
From chronic conditions - macrophages secrete ILs that stimulate hepatocytes to secrete serum a
precursor protein (SAA)
1. Kidney: walls renal arteries, GM, BM
2. Liver: in sinusoidal space of Diss
3. Spleen: forms"sago spleen



Chronic infection: TB, syphillis, leprosy
Chronic inflammatory diseases: RhA, Crohns, UC
Neoplasms: Hodgkin's, renal cell carcionoma
AH/AB Occurs with Alzheimer's disease with APP as precursor
Anaemia
Red cell precursors





Myeloblasts
Myelocytes
Early normoblasts
Late normoblasts
Reticulocytes
Anaemia
Microcytic
1. Iron deficiency
anaemia
Normocytic
Macrocytic
1. Haemolytic
1. B12 (3 year stores in
2. Anaemia of chronic
liver - functions as
disease
co-enzyme) / Folate
(3 months stores used to produce
methionine from
homocysteine)
2. Alcoholism (leading
to B12, folate), liver
damage
3. Thyroid disease
4. Renal failure
Megaloblastic Anaemia

Megaloblast = abnormal nucleated cell not usually found in the body, present
in BM and occasionally found in peripheral blood
1. B12
o
o
o
Functions as co-enzyme to produce methionine from tetrahydrofolate
3 years store
Deficiency in (1) Pernicious anaemia GPC antibodies (2) partial/total
gastrectomy (3) failure to absorp from terminal ileum
2. Folate
o
o
Tetrahydrofolate used to form methionine from homocysteine
3 months store in liver
o
Deficiency (1) inadequate intake or excess demand in pregnancy (2)
vegans (3) drugs which have an anti-folate action
Haemolytic anaemia
1. Congenital
o Membrane abnormalities: spherocytosis (spectrin), elliptocytosis,
abetalipoproteinaemia
o Abnormal Haemoglobinopathies: SCC, HbC, HbD, thalassaemia
o Enzyme deficiency: G6PD, pyurvate kinase, glutathione synthetase
deficiency
2. Acquired
o Immune
o Mechanical - artificial heart valves, microangiopathic haemolytic
anaemia
Diagnosis:



low Hb, normochromic normocytic - macrocytic (raised Red cell distribution
width)
Raised reticulocyte count
Excess unconjugated bilirubin
Haematocrit
Proportion of total blood volume that consists of red cells
Expressed as percentage / fraction
Normally = 0.4 - 0.45
Determines oxygen-carrying capacity of blood
Determines blood viscosity
Determinants
1. Red cell volume
o Blood loss
2. Plasma volume
o Loss of water
o Plasma expansion - pregnancy
Asbestos
Occupations associated with asbestos exposure


shipworkers
Builders
Clinically significant asbestos
1. White asbestos (Chrysotile)
o 90% asbestos used in industy
o Long woolly fibres: associated with fibrosis
2. Blue asbestos (Crocidolite)
o Straight short fibres: associated with malignancy, fibrosis (penetrate
more deeply into lungs and are associated with greater pathology)
3. Brown asbestos (Amosite)
o Straight long fibres: associated with fibrosis
Asbestos-related diseases




Ca Bronchus (esp blue/crocidolite)
Malignant mesothelioma
Asbesosis - fibrotic lung disease
Chronic bronchitis
Ascities
Ascities
Abnormal free fluid within the peritoneal cavity
Transudate:


Hydrostatic: cirrhosis, right heart failure, Budd-chiari (hepatic vein
obstruction)
Oncotic: loss of protein (starvation, liver failure, nephritic/nephrotic
syndrome)
Exudate:

Inflammatory: peritonitis, pancreatitis, malignancy
Atheroma / atherosclerosis
Atheroma
Accumulation of lipid within the intima of large and medium sized arteries
Aeitological factors:hypertension, smoking, hyperlipidaemia, DM, hereditary factors

Complications
1. Ischaemia
2. Infarction (from progressive occlusion, rupture of plaque leading to
thrombosis, haemorrhage into plaque)
3. Embolus
4. Aneurysm
Blood cells
Polymorphonuclear leucocytes are classed as neutrophils, basophils and oesinophils.
Neutrophils



Basophils



Eosinophils



Polysegmented nuclei (hypersegmented in
B12/folate deficiency)
Clear cytoplasm with fine granules (contain
elastase, protease, A1AT, lysosyme, lactoferrin)
Close relation with acute inflammation
Unlobulated or bilobate nuclei
Granules contain histamine, eosinophil
chemotactic factor, slow-releasing substance of
anaphylaxis
Close relation with allergic reactions/anaphylaxis
Bilobed nuclei
Bright eosinophilic granules contai: major basic
protein, eosinophil cationic protein
Close relation with parasitic infections
Platelets



Adhese to vessel wall in presence of Von Willebrand factor leading to shape
change and degranulation
Aggregates with contraction to form solid mass in vessel
Releases PGs, serotonin, TXs
Giant Cells
1. Normal
o Osteoclasts
o Syncytiotrophoblasts
o
o
o
Megakaryocytes
Skeletal muscle cells
Oocytes
2. Abnormal
o Macrophage and related giant cell
o Virus induced
o Tumour giant cells (Reed-sternberg cells in Hodgkin's = modified B
lymphocytes)
Calcification
Calcification
1. Orthotopic
o Bone / teeth
o Otoliths
2. Heterotopic
o Metastatic: occurs as a result of hypercalcaemia, in regions that secrete
acid (lung CO2, Kidney, stomach)
o Dystrophic: occurs in dead or damaged tissues in the presence of a
normal circulating calcium concentration - atheroma, scars, aortic
valve
Calculi
Calculi

Abnormal mass of precipitated solid material in a duct
1.
2.
3.
4.
5.
Prostatic (commonest: most TURP and prostatectomy specimens have calculi)
Biliary
Urinary
Pancreatic
Salivary
Principles of formation
1. Flow
o
Stasis
2. Wall
3. Constituents
o Nidus (desqumated cells, secretion, infection)
o Increased colloid / reduced solvent
o Change in pH
Complications of Calculi
(Depends on site and size)
Obstruction
Haemorrhage
Infection
Stricture
Perforation
Metaplasia/Malignant change
Cellulitis / Erysipelas / Nec fascititis
Clinical differentiation
Condition Pathology
Cellulitis Infection of the skin
and underlying
subcutaneous tissues
Erysipelas A form of cellulitis
Occurs in
immunocompromised,
young, old
Necrotising Necrotising process of
fascitits
the deep fascia
Forms

Fournier's
gangrene (of
the scrotum)
Organisms
 Staph aureus /
epidermidis
 Streptoocci

Lancefield A
B-haemolytic
streptococci

Lancefield A Resuscitation
B-haemolytic Blood cultures / wound
streptococci
swab
Antibiotics
Radical tissue
debridement
Complement Cascade
The Complement system



Management
History
Swab
IV antibiotics benpen/fluclox or
clindamycin/erythromycin
(if penicillin allergic)
Important mechanism to control infection
Promotes phagocytosis
Involved in bactericidal mechanisms


Promotes lymphocyte function
Mediates inflammation through mast cell degranulation and chemotaxis
Classical pathway





IgG or 2 IgM fix to cell membrane
C1q binds to long chains and then to C1r and
C1s
Whole activates C4 and C2. C2,4 cleaves C3
into components
C3a is chemotactic and anaphylactic. C3b is an
opsonin and also acts with C2,4 to cleave C5
C5a is chemotactic and anaphylactic. C5b binds
with C6, C, C8 and C9 to form membrane attack
complex
Coroner
Deaths that must be reported to the coroner
1. Suspicious or Unnatural
o Death unknown
o Violent / unnatural
o Suicide
o Due to abortion
o In detention / custody
Alternate pathway
 C3 activated directly
by endotoxins,
viruses, bacteria,
fungi
 Does not need
immunoglobulin
activation
o
Ill treatment, starvation or neglect
2. Medical
o Death within 24 hours of hospital admission
o Due to medical intervention (of any sort)
o During operation or before recovery
o Not been seen by certifying doctor after death or within 14 days before
death
3. Industrial
o Industrial disease or related to deceased employment
o Service disability pensioners
Cyst
Cyst
Abnormal fluid-fillled space (lined with epithelial cells) - cf pseudocyst (filled with
granulation tisse - pancreatic)
Pathological process involved
1. Congenital
o Thyroglossal
o Branchial
o Biliary
o Polycystic kidney disease
2. Inflammation
o Infection - ameoba, cysticercosis, hydatid
o Obstruction - spermatocoele, meiboniam cyst, epipdydimal
3. Degeneration
o Bone - osteoarthritis
o Cerebral cysts post infarction
4. Implantation
o Epidermal / dermal
5. Hyperplasia
o Breast cysts
6. Neoplastic
o Ovarian cysts
o Cystic neoplasms of the pancreas
Diverticula
Diverticulum

Abnormal outpouching of a hollow visucs into surrounding tissues
Classification
1. True and False
o True: all components of the viscus (tend to be congenital)
o False: Only part of wall represented (tend to be acquired) - eg. sigmoid
colon diverticulum, pharyngeal diverticulum through Killian's
dehiscence between thryopharyngeus and cricopharyngeus msucles
(components of the inferior pharyngeal constrictor)
2. Congenital or acquired
o Eg. Meckel's diverticulum - 2inches long, 2ft from ileocaecal valve,
2% population#
o Duodenal diverticula
3. Pulsation and traction
Complications
1. General
o Inflammation
o Haemorrhage
o Perforation
2. Function
o Ectopic secretion of peptic acid, as in Meckel's diverticulum
o "Blind loop" syndrome - causing vitamin deficiencies secondary to
bacterial overgrowth
3. Cellular
o Metaplasia, as a bladder diverticulum
o Malignant change as in bladder diverticula
Erosion Ulcer
Erosion

Partial loss of epithelial or mucosal surface that heals by resolution (ie.
replacement by fully functional tissue)
Ulcer

Full thickness loss of epithelial or mucosal surface which heals by repair
(replacement with fibrous tissue) with or without resolution
Factors affecting rate of healing of ulcer
1. Local
o
Persisting cause (acid secretion, continuing infection, continuing
sepsis)
o Persisting inability to detect damage (hypoasthesia, anaesthesia)
o Poor blood supply - ischaemia
o Neoplastic process (ulcerated carcinoma)
2. Systemic
o Malnutrition
o Immune deficienc: diabetes, AIDS
Gout
Purines (adenine, guanine)



are metabolised to hypoxanthine
changed by xanthine oxidase to xanthine
Further metabolised to uric acid
Pyrimidines (thymine, cytosine)

are metabolised to ammonium salts + urea.
Nucleoside = Base + ribose: Eg. RNA
Nucleotide = Base + ribose + phosphate radical
Classification of hyperuricaemia
1. Primary: absolute/relative abnormality of xanthine-hypoxanthine handling
o Deficiency of PPRT (Lesch-Nyhan syndrome) leads to inability of
xanthine/hypoxanthine to be recycled into purines
2. Secondary: increased purine breakdown with increased formation of uric acid
o Ingestion - caviar, roe
o Increased cell turnover: psoriasis, sickle cell, leukaemia, malignancy
o Decreased excretion: CRF, diuretics
Complications of gout


Joints: destructive osteoarthropathy
Renal tract - stones, renal failure from a big stone
Fistula
Fistula

Abnormal connection between two epithelial surfaces
Classification
1. Simple / Complex (associated with abscess cavity)
2. Anatomy
o Respiratory: Bronchopulmonary fistula, tracheo-oesophageal
o GI tract: tracheo-oesophageal, enterocutaneous, perianal
o Urinary tract: entero-vesical fistula, urethrocutaneous (in circumcision)
o Reproductive tract: Entero-vaginal fistula
o
o
Circulation system: arterio-venous fistula, AAAs
Salivary gland fistula (following parotidectomy)
3. High output (>500mls/day) or Low output
o Associated electrolyte disturbance / fluid disturbance
o Associated malnutrition & sepsis
4. Aetiology
o Trauma/iatrogenic (AV fistula, post surgery, tracheostomy, earings)
o Inflammatory (IBD)
o Sepsis (from anastamotic leaks, abscesses)
o Malignancy
o Radiotherapy
Examples



Earings
Perianal fistula
Enteric fistula (Crohn's disease)
Factors controlling healing
1. Local
o
o
o
o
o
o
o
Persisting cause / material
Persisting sepsis
Persisting flow through fistula
Width of fistula
Ischaemia
Epidermidisation of track
Malignant change
2. Systemic
o Nutrition, vitamin deficiency
o Immunosuppression - DM, AID
Principles in Management
Hope Hospital protocol - SNAP - Sepsis / Nutrition / Anatomy / Proceed
1. Sepsis
o
o
o
o
Remove cause
Drain abscess cavities
Avoid antibiotics
Skin protection
2. Nutrition to promote healing
o Restrict / control fluid intake (determines output of fistula)
o Total Parenteral nutrition / distal enteral nutrition
3. Anatomy
o Fistulography
o Bowel enema
o CT / MRI: define abscess cavities
4. Procedure (1) excision - karydakis procedure (2) laying open (3) seton to cut
through tract
Haemoglobinopathies
Haemoglobinopa Pathology
Blood picture
Complications
thy
Single amino acid
 Normochromic
 Haemolytic
Sickle cell
substitution
on
B
Microcytic
anaemia results
disease
chain at position 6
anaemia
in cardiac
of valine for
 Sickled cells
failure
glutamic acid
 Reticulocytosis
 Pigment
 Features of
gallstones
splenic atrophy
 Thrombosis
 Autosomal
(target cells,
and infarction coacanthocytes,
abdomen,
dominant:
Howell-Jolly
chest, splene,
homozygot
bodies)
bone
es have 90 Infection 100% HbS,
salmonella
heterozygot
osteomyelitis,
es have 20pneumococcal
40%
sepsis
Thalassaemia
Defective globin
chain synthesis causes abnormal
haemoglobin
production


Alpha
Thalassaem
ia - China,
Asia,
Africa
Beta
Thalassaem
ia Mediterran
ean, Middle





Hypochromic
microcytic
anaemia
Reticulocytosis
Target cells
Nucleated red
cells
Increased
haemoglobin F



Marrow
hyperplasia
Iron overload
(cirrhosis,
endocrine
disturbance,
pancreatitis)
Hypersplenism
- decreased red
cell survival
time,
leucopaenia,
thrombocytope
nia
East
Hamartoma
Hamartoma


Tumour-like malformation composed of haphazard arrangement of different
amounts of tissues normally found at that site ("error")
No tendency for lesion to grow other than normal growth controls of the body
Examples
1.
2.
3.
4.
5.
6.
Haemangiomas
Peutz-Jegher's polyp of bowel
Bronchial hamartoma
Melanocytic naevi
Neurofibromatosis
Tuberous Sclerosis
Morbidity from Hamartoma
1.
2.
3.
4.
5.
6.
Obstruction
Pressure
Infection
Infarction
Haemorrhage
Fracture
Hernia
Hernia

Protusion of a viscus or tissue from the body compartment in which it normally
resides into another body compartment
Classification
1. Congenital / acquired
2. Complete / partial
o Complete: inguinal, femoral
o Partial: Richters, sliding gastric
Predisposing features
1. Increased donor compartment pressure
o
o
Abdomen: inguinal, femoral, obturator, diaphragmatic, hiatus
Brain: ICP - brain herniation
2. Weakness of tissues with normal pressure in donor compartment
o Incisional hernia: poor technique, nutrition
Complications
1.
2.
3.
4.
Obstruction
Ischaemia / infarction
Pressure effects
rupture
Hyperplasia & hypertrophy
Hyperplasia
Definition
Hypertrophy
Increase in number, number, number, number,
Increase in SIZE of cells
number of cells
Breast in pregnancy
Uterus in pregnancy
Physiological Thyroid in pregnancy
Skeletal muscle with exercise
Pituitary in pregnancy (cf Sheehan's syndrome)
Overstimulation
Pathological
Graves disease
Adrenals in Cushins
Endometrium in oestrogen excess
Overstimulation
Graves disease
Cardiomyopathies
Congenital muscular
dystrophies
Inflammatory Markers
Classification of inflammatory mediators
1. Substances stored irrespective of need and released when required
o Histamine
o Serotonin
2. Substances synthesized in cells as required when inflammatory events dictate
o Leucotrines
o Prostaglandins
o Cytokines
3. Cascades that are activated as part of the inflammatory response
o Clotting cascade
o Complement cascade - opsonins, chemoattractants, anaphylactic agents
o Kinin cascade
Prime plasma-derived mediators in acute inflammation



Fibrin-related peptides and plasmin
Kallikrein and bradykinin
C3a C5a
CRP
C-reactive protein
Half-life ~6hours
Marker of acute inflammation
Protein derived produced in liver
Functionally similar to IgG (but not specific)
Ischaemia & Infarction
Ischaemia


Abnormal reduction in blood supply to or drainage from an organ or tissue
Infarction is the result of cessation of the blood supply to or drainage from an
organ or tissue
Classification of causes
1. Local
o
o
o
Arterial obstruction: thrombus, embolus, artheroma, pressure, spasm
Venous: thrombus, pressure, stasis
Capillary obstruction: vasculitis (meningococcal septicaemia, drugs),
obstruction (sickle cell)
o External pressure
2. General
o Hypoxaemia
o Anaemia
o V/Q defect
3.
Factor determining the extent of ischaemic damage in arterial obstruction
1.
2.
3.
4.
5.
Tissue involved - brain low reserve
Speed of onset
Degree of obstruction
Presence of collaterals
Level of oxygenation
6. Presence of concomitant heart failure
7. State of microcirculation
Metaplasia
Metaplasia
Change from one fully differentiated cell type to another


Can become dysplastic if the agent that caused the metaplasia persists
Can be misdiagnosed clinically
Classification
1. Epithelial
o Squamous - endocervix, bronchi, bladder, prostate
o Glandular or columnar cell: intestinal with h.pylori; gastric with
barrett's oesophagus
2. Connective tissue
o Osseous metaplasia (formation of metaplastic bone) in bladder,
bronchus
o Chondroid metaplasia (formation of metaplastic cartilage) in scars
o Myeloid metaplasia (formation of metaplastic bone marrow) - liver,
spleen, lymph nodes
Metastasis
Metastatis

Migration of cells from a malignant tumour to a site distant from the primary
Routes of Metastasis
1.
2.
3.
4.
5.
6.
Lymphatic
Haematogneous
Transcoelomic - stomach, ovary, colon, pancreas
Perineural - adenoid cystic carcinoma of salivary glands
CSF - medulloblastoma
Iatrogenic - implantation during surgery
Necrosis
Necrosis




Abnormal tissue death during life
Energy independent
Occurs as a result of factors outside the cell
Associated with inflammatory changes
Classification
1. Coagulative
o Tissue architecture preserved - kidney, heart, spleen
o Proteins coagulate rapidly from heat
2. Colliquative
o Tissues rich in lipid, lysosomal enzymes denature fats and cause
liquifaction - brain
3. Caseous
o Unstructured
o Impossible to identify tissue affected by necrosis as architecture is
destroyed - classical of TB
Fat Necrosis
Gangrene
1. Dry: mummification of tissue without infection
2. Wet: Necrosis with putrefaction caused by infection (anaerobic streptococci,
bacteroides)
Autolysis


Degradation of a cell by activation of enzymes presnet in the affected cell
(self-digestion)
May occur in necrosis or apoptosis
Heterolysis

Degradation of a cell by activation of enzymes present in cells other than the
affected cell
‹
Organisation resolution and repair
Organisation


Transformation of inanimate material (clot, thrombus, pus) into living
tissue responsive to growth control factors of the body
Achieved by replacement with granulation tissue
Resolution


Replacement of damaged tissue by fully functional tissue normally
found at that site (no scar tissue)
Found in liver, bone marrow, mucosal defects, minor injury to
epidermis
Repair


Replacement of damaged tissue by fibrosis or gliosis filling defect but
has no intrinsic specialised function relevant to organ
Occurs in most instances
Pneumonia
Definition
Inflammatory condition of the lung
Classification
1. Primary vs secondary
2. Organism
o Viral
o Bacterial
o Fungal
3. Anatomy
o Lobar pneumonia: exudate forms directly in bronchioles/aveoli
1. spills into adjacent segments via pores of Kohn
2. Confined to a lobe
3. Usually staph
4. Phases: (1) Congestion - inflammatory exudate (2) Red hepatisation
- Neutrophils and extravasated erythrocytes (3) Grey hepatisation Fibrin meshwork and degenerating erythrocytes (4) Resolution Macrophage release fibrinolytic enzymes
o
Bronchopneumonia: starts at bronchioles, extends to alveoli. Common in
extremes of age
o Interstitial pneumonia: chronic alveolar inflammation
4. Aetiology
o Hospital acquired: loss of barriers, instrumentation, impaired cough reflex,
aspiration
1. Early: - OP organisms - staph aureus, strep pneumoniae
2. Late: Gram negative - pseudomonas, enterobacter, acinetobacter,
morganella
o Community acquired
Severity score : CURB
Normal respiratory defences
1.
2.
3.
4.
Cough reflex
Mucociliary function
Aleolar macrophages
Secretory IgA
Complications of Pneumonia
1.
2.
3.
4.
Pleuritis - pleural effusion
Empyema
Lung abscess
Generalised sepsis
Prevention of pneumonia
1.
2.
3.
4.
Protection / isolation
Intermittent feeding
Controlled use of antibiotics
Regular suctioning / chest physio
Sinus
Pathological sinus


Blind-ending tract that communicates with an epithelial surface
Result of inflammatory process, usually lined with granulation tissue
Anatomical sinus

Coronary sinus


Intracranial venous sinus (cavernous sinus)
Air sinuses
Skin
Layers of the skin
Function of skin
1.
2.
3.
4.
5.
6.
Physical barrier
Filtration of light / ionising radiation
Secretion: sweat, contains Igs and is acidic due to lactic acid
Commensals - protects against pathogens
Immunological - Langerhan's cells
UV light generates vitamin D
Skin Cancer
1.
2.
3.
4.
Squamous cells
Malignant melanoma
Basal cell carcinoma
Merkel cell tumour
Risk factors for skin cancer
1. Congenital
o Familial syndromes - BK mole syndrome
o xeroderma pigmentosum
2. Acquired
o UV light - skin grading (1) chalk white burns easily (2) fair tans difficulty (3)
fair tans easily (4) olive (5) brown (6) black
o Ionising radiation
o Chemical carcinogens (tars, dyes, rubber products)
o Viruses - HPV
o Immunosuppression
Subtypes
BCC
(above
lips)




Grading

Local excision with 37mm margin

Local excision with 510mm margin +/block dissection of
draining lymph nodes
Breslow Thickness
<1mm
1 - 2mm
2 - 4mm
>4mm

Clarke Levels

Local excision with
10mm margin if 1mm
depth
Local excision with
20mm margin if 2mm
depth
Local excision with
30mm margin if 3mm
depth
Nodular
Cystic
Pigmented
Superficial spreading
SCC
(below
lips)
MM





Superficial spreading
(64%)
Nodular (12-25%)
Lentigo maligna (715%) with best
prognosis
Acral lentiginous (1013%)
Amelanotic
I: epidermis
II: papillary dermis
III:
papillary/reticular
junction
IV: reticular dermis
V: subcutanous fat
Spread of infection
Sources of infection
1. Animals
o
o
Treatment
Humans - TB, MM, influenza, neisseria, MRSA
Animals - zoonoses, vets, mos

2. Plants
o
Soil
3. Environment
o Soil
o Air
Routes of infection - the "I"s





Inhalation / droplet spread
Ingestion
Intercourse
Innoculation - catherisation, injection, insects
In-utero: trans
Endemic: Exists continously in a population, usually of low prevalence
Epidemic: Sporadic disease in a population, usually involves large numbers of people
Pandemic: Epidemic that affects many parts of the world
Syndromes
Lipoma
Lipoma
1. Commonest benign tumour of mature fat cells (adipocytes)
o Occur anywhere in body
o Commonest in subcutaneous layer of skin (neck and trunk)
o Malignant change is thought to not occur
2. Multiple painful lipomas are known as adiposis dolorosa or Dercum's disease
(associated with peripheral neuropathy)
3. Variants
o Liposarcomas arise de novo (and not via lipomas)
1. Classification
1. Well-differentiated: ring or long markers, chromosomes
derived from long arm of Chromosome 12
2. Myxoid and round cell (poorly differentiated)
liposarcoma
3. Pleomorphic liposarcoma: characterised by complex
karyotypes
o Angiolipomas have prominent vascular component
o Hibernomas: tumours of brown fat cells - seen in hibernating animals
o Cowden's disease: association of lipoma, palmoplantar keratoses,
multiple fascial papules, oral papillomatotis, vitiligo with involvement
of the thyroid and disgestive tract
o Bannayan-Zonana syndrome: rare AD hamartomatous disoder:
multiple lipomas, macrocephaly, haemangiomas
4. Treatment
o Non-surgical: watch and wait
o
Surgical: (indications are pain / cosmesis) - options: (1) suction
lipolysis via small remote incision (2) excision under LA
Inspection
1. Discoid / hemispherical swelling
2. May appear lobulated
3. Look for scars (recurrent lipoma / Dercum's disease)
Palpation
1.
2.
3.
4.
Lobulated
Soft / firm depending on nature of fat in lipoma
If soft and large may be fluctuant
Slip sign: manner in which lipoma tends to slip away from examining finger
on gentle pressure
5. Skin freely mobile over the lipoma (compared to sebaceous cysts)
6. Determine if lipoma is in skin or intramuscular (disappears on contraction of
muscle)
Completion
1. Life impact: cosmesis
2. Similar lumps elsewhere (Dercum's disease)
Thrombosis / Clotting
Thrombus



Solid material formed from constiuents in flowing blood
(A blood clot inside a blood vessel when the patient is alive)
Function of platelets + clotting cascade
Factors contributing to thrombosis (Virchow's triad)
1. Wall
2. Flow
3. Constituents
Clot


Solid material formed from constituents of stationary blood
Primarily function of clotting cascade
Urinary tract calculi
Type
Prevalence
Composition
Calcium oxalate
75%
Ammonium phosphate
15%
Urate
5%
Cysteine
3%
Spiky / mulberry shaped
Caused by hypercalciuria (moans, stones, psychic groans)
Rare enzyme deficiency
Increased oxalate absorption: coeliac, diverticulae of bowel,
Associated with proteus infection
"Staghorn calculi" (from urease)
Primary gout: HGPRT deficiency (Leesh-Nyhan)
Secondary gout: increased purine breakdown - tumours, RT,
Results from primary cysteinuria, inborn error of metabolism
Management
1. History: precipitants, family history, personal history
2. Examination
3. Investigations
o Urine dipstick - blood, nitrates (UTI cause)
o U/Es, serum electrolytes, WCC, CRP
o KUB - 90% renal tract stones are radio-opaque (calcium, ammonium ,
cysteine) - urate/xanthine stones radiolucent
o IVU: determines degree / level of obstruction (hydronephrosis) - sites
for blockage: (1) renal pelvis (2) pelvic brim (3) insertion into bladder
- contrast contraindicated in pregnancy, allergy, anaphylaxis, raised
serum creatinine
o USS: - no contrast, detects stones >5mm, determines hydronephrosis
and obstruction
o CT Abdo: identifies radio-opaque and lucent stones, secondary signs of
obstruction
4. Analgesia - morphine, pethidine, NSAIDs
5. Hydration
Definitive treatment
<4mm


4-6mm
Watch and wait
90% pass
spontaneously

>5mm
60% pass
spontaneously


Extra-corporeal
shockwave
lithotripsy: stones <
2cm in upper or
lower 1/3 (middle
difficult to visualise
apparently) contraindicated in
pregnancy,
aneurysms,
pacemakers
Ureteroscopy
+lithotripsy: stones
in lower 1/3
collected using
stone basket or



fragmented and
pieces collected
Percutaneous
nephrolithotomy:
stones > 2cm in
renal pelvis - tract
made
percutaneously into
renal collecting
system and stone
extracted (large
stones can be broken
up first)
If obstructed percutaneous
decompression + JJ
stenting
Open surgery (less
than 1% patients) for stones that just
are bad to the bone
Urinary tract infections
Urinary tract infection


Infection of bladder, ureter, kidney (via renal pelvis)
NB. Urethral infection is considered a STD
Predisposition
1. Anatomy
o Female anatomy: proximity of urethra to anus
o Congenital abnormalities affecting flow: ectopic vesicae, ureteric
duplication, urethral valves, congenital stricture, VUJ reflux
2. Urine stasis
o Mechanical obstruction: hydronephrosis, stricture, stone, neurogenic
bladder, prostatic hypertrophy
o Prostatic enlargement
3. Instrumentation
o Indwelling catheters
4. Systemic disease
o
o
Diabetes
Immune deficiencies
Organisms

Enterococci: E.coli, proteus, pseudomonas, klebsiella, staph aureus
Diagnosis



Urine dipstick: RBCS, WCC, nitrates
Microscopy
Culture
GI pathology
Alcohol-related diseases
Metabolism of alcohol



Microsomal ethanol oxidising system (MEOS)
Alcohol dehydrogenase
Catalase
Biochemistry/Haematology


Raised GGT
Macrocytosis
Laryngeal disease associations



Laryngeal inflammation
SCC larynx
SCC pharynx / oesophagus
Hepatic effects of chronic alcohol



Fatty liver
Alcoholic hepatitis
Cirrhosis: End stage of all chronic liver insults (1) nodules (2) fibrosis (3)
distorted architecture

Hepatocellular carcinoma
GI associations



Gastritis/erosions
Pancreatitis
Carcinoma of pancreas
CNS effects




Dis-inhibition, violence, trauma, chronic malnutrition
Cerebellar degeneration
Korsakov's psychosis
Wernicke's: antegrade amnesia (?related to thiamine deficiency)
Colorectal pathology
Layers of the bowel wall
Mucosa
Muscularis mucosae
Submucosa
Muscularis propria
Subserosa
Serosa
Dukes staging
A:
B: Penetrating wall (including touching wall)
C1: Local nodes/peri-rectal nodes
C2: Apical nodes
D: Distant spread
Dukes staging system does not take into account the lesion that extends laterally
(rather than through wall). Therefore one can have a massive superficial tumour.
Diverticular disease
Diverticulum [pathology]
Outpouching of colonic wall which results from herniation of mucosa through
muscular wall
1. Occur at sites where mesenteric vessles penetrate bowel wall
2. Lage of dietary fibre in western diets results in low stool bulk which
stimulates increased segmentation of colonic musculature, resulting in
hypertophy
3. Increased intraluminal pressure results in herniation
Complications of diverticular disease
1.
2.
3.
4.
Haemorrhage
Inflammation - diverticulitis
Obstruction from diverticular stricture
Fistulation to bladder, vagina or skin
o Pneumaturia
o Faecaluria
o Chronic urinary tract infections
5. Perforation
6. Pericolic or pelvic abscess
Hydatid disease
D: The result of infection with adult tapeworm (Echinoccocus granulosus)
G: Common in mediterranean
P: Large parasitic cyst grows slowly and asymptomatically



Can have pressure effects on organs
Can Rupture (can also release daughter cysts within them)
Cysts can become infected with bacteria
Life Cycle




Ingestion of canine tapeworm eggs (dogs are asymptomatic)
Eggs hatch in duodenum + embryos cross mucosal membrane
Travel via portal blood supply to liver
Primary site of infection is the liver (can affect any organ in body)
S: Can present as acute abdomen from minor trauma from rupture


S:
Rupture: pain
Into biliary tract: Obstructive jaundice, cholangitis
I: Diagnosis is by serology and scans



Serology/ELISA assay - Enzyme Linked ImmunoSorbent Assay for antibodies
to hydatid antigen
USS: Multiloculated cysts
CT: "floating membrane"
T: Albendazole chemotherapy. Surgical enucleation is required occasionally.



Chemotherapy: Albendazole/Mebendazole
Percutaneous hypertonic saline and alcohol
Surgery: (1) complete resection (2) local excision of cysts (3) de-roofing of
cyst with evacuation of contents. Contamination of peritoneal cavity at time to
surgery should be avoided by continuing drug therapy.
Inflammatory bowel disease
Causes of Colitis
1.
2.
3.
4.
5.
Infection
Inflammation - Crohn's, UC
Ischaemia
Radiation
Drugs (antibiotic induced pseudomembranous)
Definition
Crohn's
Ulcerative Colitis
 Disease of inappropriate activation of gut mucosal immune
system
 Driven by normal bowel flora
 ?Defective barrier mechanism
Incidence 40/100,000
Age
Sex
Geography
Aetiology
 Genetics
 Smoking
 Diet: low fibre
 Immune mechanisms
Pathology


Transmural inflammation
Serositis common
80/100,000
20 - 35 years


Genetics
Smoking protective

Mucosal inflammation (with
crypt abscesses
Serosa normal

Macroscopi
c


Anywhere along GIT (but
esp terminal ileum)
Patchy "skip lesions"

Starts at rectum and
progresses proximally
(ileum 10%)



"Cobblestone" appearance
with fissuring
Strictures common
Fistulae common




Continous lesions
No fissuring
Strictures uncommon
Fistulae uncommon
Microscopi
c

Non-caseating granuloma
(aggregation of
macrophages)

Inflammation - neutrophils,
macrophages
Prognosis

Possible malignant change

Malignant change well
recognised

Severe acute colitis
1.
2.
3.
4.
5.
Frequent stools >6/day
Fever, tachcardia
Systemically "unwell"
Rectal bleeding
Low albumin



Intermittent relapsing colitis
Chronic persistant colitis
Asymptomatic
Symptoms
Signs



Skin: Erythema nodosum,
pyoderma gangrenosum
Eyes: iritis
Joints:
Investigatio
ns
Treatment Depends on
1. Site of disease
2. Type of disease
3. Disease severity
Medical treatment
1. 5-ASA (blocks
prostaglandins and
leukotrienes)
2. Steroids
3. Immunosuppressants Azathioprine
(mercaptopurine derivative),
infliximab (anti TNF
antibody), methotrexate
Endoscopic grading
Depends on
1. Site of disease
2. Type of disease
3. Disease severity
Medical treatment
1. 5-ASA (blocks
prostaglandins and
leukotrienes)
2. Steroids
3. Immunosuppressants Azathioprine
(mercaptopurine derivative),
infliximab (anti TNF
antibody), methotrexate
(antimetabolite)
Indications for sugery



Limited Resections
Strictureplasty
Bypass procedures
1. Elective
o Chronic symptoms
despite medical
therapy
o Malignancy
o Fistulating disease
o Chronic obstruction
2. Emergency
o Clinical: Severe
colitis, haemorrhage
o Biochemical: WCC,
CRP
o Radiographical:
Perforation
(antimetabolite)
Indications for sugery



Total colectomy + ileostomy
+ mucous fistula
Proctocolectomy + ileoanal
pouch (depends on adequate
anal musculature)
Types of pouch: S-pouch, Jpouch, Four-loop W-pouch
1. Elective
o Chronic symptoms
despite medical
therapy
o Malignancy
2. Emergency
o Clinical: Severe
colitis, haemorrhage
o Biochemical: WCC,
CRP
o Radiographical:
Perforation, toxic
megacolon
Peptic ulcer disease
Common aetiological factors
1. H.pylori - 90% duodenal ulcers, 70% gastric ulcers
2. NSAIDS - systemically suppress (protective) prostaglanding production
3. Systemic illness - leading to stress ulcers: Curling's in burns / Cushing's in
trauma
4. Cigarette smoking
5. Chronic disease
Complications of peptic ulceration
1. Perforation (anterior wall ulcers - cause peritonitis): needs oversewing
2. Haemorrahge (posterior wall ulcers - erode gastoduodenal artery): needs
under-running
3. Gastric outlet obstruction (duodenal ulcers - stricture of first part of
duodenum)
4. Recurrent ulceration
Confirmation of perforated peptic ulcer
1. History - risk factors (smoking, medications)
2. Examination - rigid abdomen, peritonitis, absent bowel sounds (may be no
clinical signs in elderly)
3. CXR - free air under diaphragm (85% of cases)
4. Serum amylase to exclude pancreatitis
5. ECG to exclude MI
Polyp
Polyp
Tumour protruding from the epithelium of an organ
Classification of Polyps
1. Congenital acquired
2. Shape
3. Aeitiology
o Metaplastic or hyperplastic
o Inflammatory - UC
o Hamartomatous - Peutz-Jegher's, juvenile retention polyps
o Neoplastic
Complications
1.
2.
3.
4.
5.
6.
ulceration
haemorrhage
infection
intesussception
Function effects: protein loss, potassium loss
Malignant change
Bowel Polyp syndromes
1. Peutz-Jehger's
2. Familial adenomatous polyposis
Pyloric stenosis
Clinical features


Familial tendency, 20% affected parents
Especially male children
Pathophysiology of Alkalosis in Pyloric stenosis
1. Stomach: Loss of gastric acid secretions (rich in protons and chloride)
2. Pancreas: Reduced pancreatic juice secretion (reduced load in duodenum) Pancreatic juice rich in bicarbonate which is retained
3. Volume depletion maintains alkalosis by leading to bicarbonate absorption
over chloride
4. Kidneys: Increased uptake of bicarbonate at renal tubules (due to loss of
chloride) to maintain electrochemical neutrality
Volvulus
Volvulus
Malrotation of a segment of intestine about its own mesenteric axis
Results in
1. Partial / complete obstruction of lumen + proximal dilation
2. Compromise of blood flow leading to ischaemia
3. Infarction from venous congestion
Pre-disposing factors
1. Anatomy - long narrow-based sigmoid mesentry prone to twisting
2. High residue diet
3. Chronic constipation
Areas affected
1. Small bowel
2. Caecum
3. Sigmoid colon (75%)
Management
1. History
2. Examination
3. Investigations
o AXR - dilated loops of bowel extending diagonally
o
ABG - acidosis, lactate
4. Treatment
o Conservative: if no features of ischaemia (80% will resolve)
o Sigmoidoscopy - diagnostic and therapeutic
o Flatus tube insertion (can be left for 2-3 days)
o Laparotomy for decompression (untwisting) with excision of
redundant sigmoid colon (sigmoid colectomy + primary anastamosis)
Haematology
Disseminated intravascular
coagulopathy (DIC)
Cytokine-mediated disease
Causes
1.
2.
3.
4.
5.
6.
Tissue injury - burns, trauma, fat embolus
Infections
Vascular/perfusion disorders: vasculitis, PAN, ARDS
Haematological disorders
Neoplasms
Systemic: pancreatitis, burns, embolism, hypothermia
Recognition intraoperatively / clinically
1.
2.
3.
4.
5.
6.
Understand risk factors
Bleeding / oozing which is difficult to control
Hypotension
Tachycardia
Low oxygen saturations
Bleeding from ususual areas - venepuncture, cannulation sites, epistaxis,
haematuria from uncomplicated bladder catheterisation
Diagnosis
1.
2.
3.
4.
5.
Low platelets
Low plasma fibrinogen (used up in coagulating)
Increased PT and APTT (clotting factors used up)
Increased FDPs / D-dimers (more degradation products)
Haemolysed fragmented red cells
Lymphoma
Lymphoma

Malignant tumour of lymphoid tissue
Presentation
1. Primary Tumour
o Painless progressive lymph node enlargement
o SVC obstruction
2. Systemic effects
o Malaise
o Weight loss
o Splenomegaly / Hepatomegaly
3. Metastatic features
o Bone pain
4. Paraneoplastic syndromes
Classification
Cellular
Clinical features
Hodgkin's Lymphoma
 Dorothy Reed-Sternberg
cells
 Polymorphic



Bimodal age distribution
Step-by-step spread
80% curable
Non-Hodgkin's Lymphoma


B-cell tumour
Monomorphic



Peak 50 years (older)
Random spread
Poor prognosis
Rye Classification
Classification
(grading)
1.
2.
3.
4.
Lymphocyte predominant
Nodular sclerosing
Mixed cellularity
Lymphocyte deplete
Ann Arbor System


A - Absence of systemic symptoms (wt loss, fever)
B - Presence




Stage I: one node
Stage II: many nodes (same side)
Stage III: Both sides of diaphragm
Stage IV: Metastatic spread
Staging
Diagnosis
1. History
2. Examination
3. Imaging
o CXR
o IVU - retroperitoneal nodes compress renal
calyces
o CT scan
4. Tissue diagnosis
o Node excision biospy [Splenectomy previously]
Treatment
Radiotherapy + Chemotherapy
Platelets
Platelets
1. Derived from megakaryocytes
2. Functions - adhesion, activation, secretion, aggregation
3. Release: serotonin, adrenalin, ADP, prostaglandins, thromboxanes
Classification of platelet abnormalities
1. Disorders of number
o Thrombocytopenia: bleeding - petechiae, ecchymosis, epistaxis
o Thrombocythaemia: splenomegaly, haemorrhages, thrombotic episodes
2. Disorders of function
o Thrombasthenia
Polycythaemia
Classification
1. Primary
o Polycythaemia rubra vera: myeloproliferative disease
2. Secondary
o Appropriate EPO excess: hypoxia (emphysema, lung diseases), CCF,
high altitude
o Inappropriate EPO excess: renal neoplasms
3. Relative
o Apparent polycythaemia because of a reduction in plasma volume
AIDS
Human Immunodeficiency Virus

RNA retrovirus



requires reverse transcriptase
Core protein RNA surrounded by glycoprotein envelope
Infects cells via CD4 receptors (T-helper)
Neoplastic associations
1. Lymphoma
o B-cell NHL / T-cell NHL
o Aggressive form HL
2. Kaposi's sarcoma
3. Skin cancer
o SCP
o SCC: anus, vulva
4. Laryngeal neoplasm
o SCC larynx
Surgical Relevance




Bacterial enteritis
Haemorrhage from KS of GIT
CMV infection leading to megacolon
GIT lymphoma
Hypersensitivity reactions
Type
I



Type
II



Type
III

Immediate / Anaphylactic
IgE linkage by an antigen leads to release of mast cell contents
(histamine, 5HT, heparin, PAF, chemokines)
Minutes
Eg. eczema, asthma, allergic rhinitis
Cytotoxic
Antibody in serum reacts against tissue components resulting in cell
death from (1) complement action (2) destruction by killer T-cells (3)
phagocytosis by macrophages
Minutes-hours
Eg. transfusion reactions
Immune complex
Immune complex formed that activates complement/platelets - cause


Type
IV


damage by formation of membrane attack complex (MAC) and
enzyme release from inflammatory cells
Hours
Eg.
Delayed
Mediated by sensitised T-lymphocytes
Days TB, organ transplants
Immunodeficiency
Body's defences
1. Innate
o
o
o
Skin
Complement
2. Interactive
o Cellular
o Antibody
Immunisation
1. Active or Passive
o Active: pre-formed antibodies (HBsAG, immunocompromised patients
with shingles, botulism, rabies)
o Passive: transplacental transfer of IgG protects for first 6 months of life
2. Natural or artificial
o Natural: following infection
o Following vaccination
Different types of vaccinations
1. Live attenuated: - BCG, sabine for polio, MMR
o Long lasting immunity
o Potentially dangerous in immunocompromised patients
2. Killed organisms: typhoid, cholera, pertussis
o Smaller immune response: usually boosters are required
3. Toxoid
o Not the infection but the effects of toxin that result from infection (eg.
Tetanus toxoid)
4. Other bacterial constiuents
o Surface polysaccharides and proteins
Immunoglobulin
1. Antigen binding sites (light and heavy chain regions)
2.
3.
4.
5.
Complement activation parts
Immune adherence
Heavy chains determine the class of immunoglobulin - GAMDE
Light chains are kappa- or lambda- irrespective of the immunoglobulin class




IgG: most important Monomeric: activates complement, binds to killer t-cells
IgA: present in secretions of BIT, respiratory tract; Dimer with J-chain
IgM: Largest - Pentamer
IgE: Monomer bound to mast cells
Immunodeficiency
1.
2.
3.
4.
1. Acquired
o Drugs
o Infections
2. Congenital
Bruton's X-linked gammopathy
T-cells: Thymic atrophy in Di-George anomaly
SCID
Lymphoma
Infections in Compromised patients
1. Congenital
o Bruton type hypogammaglobulinaemia
o Di George type
o Combined
o Deficiency of neutrophil function in chronic granulomatous disease
2. Acquired
o Infections: AIDS
o Drugs: steroids, cytotoxics
o Diabetes (also because glucose as a culture medium in urine and on
skin)
o Instrumentation - lines, catheters, ventilation
o Prosthesis: hips, knees, heart valves
Sources of infection
1. Endogenous
o Colonic bacteria
o GIT
o Skin
2. Exogenous
o Foamites
o
o
o
Other people
Transplanted tissues
"Opportunist"
Metabolic / Endocrine
Adrenal pathology
Layers of the adrenal gland
Glomerulosa: Salt: aldosterone
Fasiculata: Sugar: glucocorticoids
Reticularis: Sex hormones - dehydroepiandrosterone / oestradiol
Medulla - catecholamines
Mechanism of action of Steroid hormones
1. Intracellular receptor binding
2. Results in gene stimulation
Hormone release (RAS)
1. Glucocorticoids
o ACTH
2. Aldosterone
o Renin (stimulated by low BP, sympathetics); Low Na; Hyperkalaemia
o Renin - activates Angiotensinogen
o Angiotensinogen activates angiotensin I
o Angiotensin I to Angiotensi II by ACE (in the lungs)
o Stimulates aldosterone release
Cushing's syndrome / Disease

Hypercortisolaemia (Cf disease - hypercortisolaemia secondary to pituitary
adenoma secreting ACTH)
Causes:
1. ACTH - pituitary tumours, ectopic ACTH from oat cell, carcinoid, pancreas
2. Steroid secreting adenoma
3. iatrogenic steroids


Cushingoid features (1) Head and neck - moon face from fat and oedema, acne
from testosterone effects, male pattern baldness, hisutism in ladies (2) Chest
and trunk - buffalo hump from fat distribution, central obesity, striae,
ecchymoses from capillary fragility (4) Limbs - muscle wasting from cortisol
effect
Endocrine effects
1.
2.
3.
4.
Fat / salt handling
Diabetes
Secondary osteoporosis
Amenorrhoea from suppression
Hyperaldosteronism
1. Primary: Conn's syndrome - autonomic secretion from adenoma
o Salt/water retention leads to hypertension
o Hypernatraemia / hypokalaemia / metabolic alkalosis (in association
with hypokalaemia)
o Rx: Spironalactone (Aldosterone antagonist)
2. Secondary: RAS activation following dehydration
Adrenocortical insufficiency / Addison's disease

Bilateral destruction of the layers of the adrenal gland
1.
2.
3.
4.
5.
Infection - TB, fungi, Friederichsen-Waterhouse (meningococcal emboli)
Deposition - haemochromatosis, amyloid, malignancy
Auto-immune
Drugs - adrenolytic drugs (ketoconazole), steroid withdrawal
Iatrogenic- Adrenalectomy

Clinical features
1. General: Weight loss, malaise
2. Skin: - Hyperpigmentation due to POMC (pro-opio melano cortin) from
anterior pituitary with increase in MSH and ACTH
3. Biochemical: Hyponatraemia, hyperkalaemia, increased ACTH, decreased
aldosterone and cortisol
Adrenal Medulla
Hormones produced
1. Catecholamines: produced from tyrosine (tyrosine hydroxylase)> DOPA
(Dopa decarboxylase)> Norad (Dopamine B-hydroxylase)> Dopamine
(Phenylethanolamine-N-methyl-transferase)> Adrenaline
2. From chromaffin cells: Dopamine, somatostatin, substance P, enkephalins
Innervation: Ach from pre-ganglionic sympathetic fibres
Effects of hormones:
1. Cardiovascular effects
o Hypertension, tachycardia
2. Respiratory
3. GI:
4. Metabolic
o Carbohydrate - cause hyperglycaemia (1) stimulates gluconeogenesis
(2) glycolysis (3) inhibit release or insulin - mediated via alphareceptors
o Lipids - stimulates lipolysis
Diabetes
Diabetes Mellitus
Due to absolute / relative insulin resistance
[Pancreas]
Diagnosis
1. History: polyuria, polydipsia, unexplained weight loss
2. Plus:
o RPG: >11.1
o FPG: > 7.0
o GTT: >11.1 2 hours after 75g oral glucose
Complications
1. Arterial disease
2. Renal disease
3. Skin disease
4. Anaesthetic complications
5. Eye disease: cataracts, retinopathy, infections
6. Bone/Joint disease - septic arthritis, osteomyelitis
7. Systemic: immune deficiency
Clinical Features
1. Skin
o
o
o
o
Necrobiosis lipodica diabeticorum
Leg ulcers
Fat atrophy
Skin infection
2. Eyes
o
o
Diabetic retinopathy
Cataracts
3. Peripheral vascular
o Amputations
o Gangrene
4. Neurological
o Charcot's joint
o Diabetic neuropathy - dorsal column disease
5. Renal disease
o Skin pigmentation
o Hypertension
o AV fistulae
Hyperparathyroidism
Classification
Causes/sources

Primary - tumour


Secondary - to
hypocalcaemia



85% parathyroid
adenoma
15% parathyroid
hyperplasia
1% carcinoma
Serum
Complications
biochemisty
 Bone disease:
pathological
fractures
High calcium
 Psychic effects
 Abdominal pains
Low
 Renal effects:
phoshate
calculi,
nephrocalcinosis
Low calcium
Renal - decreased
metabolism of
High
vitamin D
phosphate
Dietary deficiency
Decreased

Tertiary autonomous
adenoma
sunlight
Pregancy increased demands
High calcium
Low
phosphate
Multiple Endocrine Neoplasia
Type I: pituitary, pancreas, parathyroid (PPP)
Type IIa: parathyroid, thyroid, phaeochromocytoma (PTP)
Type IIb: phaeochromocytoma, thyroid, neuroma (PTN)
Paget's disease of bone
Osteitis Deformans









D: Second most common metabolic bone disease (first is osteoporosis)
characterised by excessive / disorganised bone formation and resorption
I/A: Increasing incidence with age - 3-4% over 40 years, 10% 85+
S: More common in men than women
G: More common in the west, less common in east asian countries
A: Unknown but though to be persistent infection in bone from a virus
(Measles, mumps, RSV)
P: Alternating phases of rapid bone resorption/formation
M: Long bones have thicked shafts/deformities, cysts and stress fractures seen.
May be areas of localised softening - "osteoporosis circumscripta".
M: (1) Osteolytic phase - clasts produce excavations which are filled with
vascular fibrous tissue (2) Mixed lytic-sclerotic phase - blasts lay down woven
bone which is subsequently resorbed by osteoclasts (3) Quiescent
osteosclerotic stage - clasts less active, eroded areas filled with brittle woven
bone
P
Clinical features


Usually asymptomatic
Bone: 15% monostotic, 85% polyostotic
1. Long bones - become bowed/deformed
2. Cranium - compression of cranial nerves as pass through foramina (8th leading to deafness), compression of nerve roots (causing pain)
3. Pathological fractures
4. Osteosarcoma (1%)

Cardiac
1. High output cardiac failure - most common in polyostotic disease (increased
bone blood flow)
Investigations



Radiology
Increased ALP (reflects osteoblastic activity)
Plasma calcium normal/raised
Treatment



Control pain
Suppress bone turnover - bisphosphonates, serum ALP for measuring disease
progression
Surgery - pathological fractures, joint replacement, nerve/cord decompression
Pancreatitis
Acute Pancreatitis
Inflammation of the pancreas
[Functions of the pancreas]
Causes
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Gallstones 45%
Ethanol 35%
Trauma
Steroids
Mumps, coxsackie
Autoimmune
Scorpion venom
Hypercalcaemia (activates enzymes), hyperlipidaemia
ERCP
Drugs (steroids, thiazides)
Pathophysiology
1. Activation of proteolytic pro-enzymes contained within pancreas
2. Triggers autodigestion
3. Results in severe inflammatory reaction
o Inflammed acinar cells and invading leucocytes produce cytokines (IL-1) and
TNFalpha
o Cytokines mediate systemic inflammatory response syndrome (SIRS)
4. Persistant inflammation leads to "pancreatic pseudocyst"
o Collection of fluid rich in pancreatic secretions enclosed within a cyst lined
with granulation tissue (as opposed to epithelium)
o If < 5cm will resolve spontaneously; if > 5cm may beed surgical intervention
and drainage
o Conservative therapy needed for 4-6 weeks to allow cyst wall to mature
o Surgical treatment: - Radiology-guided percutaneous drainage; endoscopic
drainage; internal drainage
Clinical presentation
1. History
o
o
severe epigastric pain radiating to back and eased by leaning forwards
Accompanied by nausea and persistent vomiting
2. Examination
o tenderness with rigid abdomen and absent bowel sounds
o Abdominal distension due to ileus
o bleeding in fascial planes: Grey-Turner's sign (flanks); Cullen's sign (periumbilical)
3. Investigations
o Shock- tachycardia
o Low pO2
o High BM etc...
o High serum amylase (>500U) or serum lipase
o AXR: "sentinel loop", CXR - exclude perforation
Ranson Criteria
APACHE III score (acute physiology and chronic health evaluation)
Glasgow (Imrie) scoring system





PaO2 < 8kPa
Age > 55years
Neutrophils > 15 x108/l
Calcium <2.0 mmol/l - saponification
Raised Urea >16mmol/l



Enzymes: AST/ALT >600; LDH >600
Albumin <32g/litre
Sugar > 11mmol/l
Severe if score 3 or more
Should be managed in HDU setting
Complications
1.
2.
3.
4.
5.
Pancreatic abscess
Pancreatic pseudocyst
Severe destructive pancreatic haemorrhage
Duodenal obstruction
Chylous ascites
Chronic Pancreatitis
1. Chronic inflammatory disease of pancreas
2. Irreversible glandular destruction
o Early: may appear "normal"
o Late: fibrosis and calcification
o Cysts form within pancreas with duct dilation
3. May occur as result of recurrent acute pancreatitis
Causes
1.
2.
3.
4.
5.
Alcohol
Smoking
Hereditary
Hypercalcaemia
Duct obstruction
o Strictures
o Gallstones
o Cystic fibrosis
Clinical features





Amylase usually normal
Interferes with life and leads to opiate abuse
Loss of exocrine function - malabsorption, steatorrhoea
Loss of endocrine function - diabetes
Imaging (CT/MRI-pancreas protocol): demonstrates calcification
Management
1. Dietary modification - low fat, alcohol abstention
2. Avoid opiates
3. Pancreatic enzyme supplements: 4. Correct endocrine disturbance
Pituitary hormone disorders
The pituitary hormone disorders
Hormone
Excess
Growth Hormone Acromegaly
Deficiency
Causes


GH secreting pituitary adenoma
Ectopic GH from pancreas/lung/intestine
carcinoma
Surgical Associations






Osteoporosis
Orthodontic procedures
Large bowel polyps/carcinoma
Gallstones/GB disease
Increased incidence of hernias
Diabetes mellitus
Sjogren's syndrome
Pathology
1. Autoimmune disorder - 90% occur in women, average age 50 years
2. Intermittent or constatn swelling of one or all of hte salivary glands
3. Diagnosis (at least 2/3)
o Keratoconjunctivitis sicca (dry eyes)
o xerostomia (dry mouth)
o associated connective tissue disorders
4. If no associated connective tissue disorders are present, this is known as
primary Sjogren's disease
5. Pathology:
o lymphocyte-mediated destruction of the exocrine glands secondary to
B-cell hyper reactivity and associated loss of suppressor T-cell activity
o x40 increased risk of developing lymphoma, usually B-cell nonHodgkin's type
o
Antibodies: anti-salivary Ab, rheumatoid factor, anti-SSA-Ro and antiSSB-La
6. Investigations
o Schirmer's tests for xerophthalmia (strip of filter paper inserted into
each fornix and hyposecretion confirmed by wetting of less than 5mm
in 5 minutes - normal is 15 mm)
o Slit-lamp examination of the cornea
o Lip biopsy for histological examination of the minor salivary glands
Testicular cancer
Classification
1. Primary 95%
o Germ cell (seminoma, teratoma)
o Non-germ cell
2. Secondary 5%
o Lymphoma
o Metastatic (lymphoma, leukaemia, melanoma)
Risk factors
1.
2.
3.
4.
5.
Testicular maldescent (1/20 have malignancy)
Mumps orchitis
Trauma
Maternal oestrogen exposure
Genetics: 12p chromosomal abnormalities
Royal Marsden Hospital Staging system





I: Confined to testis
II: Confined to testis but with persistently raised tumour markers
III: Infradiaphragmatic node involvement
IV: both sides of diaphragm
V: Extralymphatic metastases
Management
1. History
o Risk factors - trauma, mumps, maledescent, maternal oestrogen
o Genetics
2. Examination
o Regional nodes - drain to para-aortic
3. Investigations
o Blood tests: Tumour marker assay, aFP, LDH, HhcG
o CXR: Pulmonary metastases
o USS scrotum
o Chest / abdominal CT - detection of metastases in retroperitoneum and
mediastinum
4. Treatment
o Scrotal exploration: if diagnosis is uncertain; scrotum can be explored
and possible tumour biopsy
o Orchidectomy: if there is any doubt
o Radiotherapy (seminomas highly radiosensitive)
o Chemotherapy for advanced stage disease
Thyroid / Goitre
Functional unit of the thyroid
Follicle




Epithelial cells surround central colloid
Follicular cells lie adjacent to a vein / capillary
Produces 80% T4 and 20% T3 (rest of T3 is converted in the peripheries)
T3 is the active form
Parafollicular cells

Secrete calcitonin
T3/T4 Physiology
1. Iodine transported across cell membrane, transfered to colloid, then linked to
tyrosine
2. Tyrosine iodinated to mono-iodotyrosine + di-iodotyrosine (bound to
thyroglobulin)
3. Coupling results in T3 and T4
4. T3/T4 + thyroglobulin transported into cell as colloid droplets; then separated
from TG
5. T3/T4 released into circulation (bound to albumin, thyroxine binding globulin
[different from thyroglobulin])
Goitre


Any enlargement of the thyroid gland
Seen as midline swelling that moves with swallowing
Single

Adenoma
Multinodular
 Adenoma
Diffuse
1. Painful

Carcinoma

Carcinoma
o De Quervain's thyroiditis
2. Painless
o Iodine deficiency
o Goitrogens - in foodstuffs
o Thyroiditis
o Infiltration - sarcoid
o Dyshormogenesis
Hyperthyroidism
1. Immune
o Graves
o Hashimoto's
2. "Physiological"
o Pregnancy
3. Drugs
o Thyroxine replacement (in block and replace)
o Amiodarone
4. Carcinoma
o hyperactive nodule
o Follicular carcinoma
o Papillary carcinoma
o Struma ovarii - thyroid tissue in dermoid cyst
o Basophil adenoma of pituitary
Thyroid disease workup
1.
2. Radioactive scanning (not a very useful test really is it?!)
o Hot nodule: 95% benign
o Cold nodule: 80% benign
Microbiology
Amoebiasis
Diseases caused by amoebae



GIT: Amoebic dysentry, inflammatory polyps, liver abscess
Skin: anal/vulval ulceration
CNS: abcesses, meningoencephalitis (Naegleria fowleri)
Antimicrobials
Tazocin: contains piperacillin + B-lactamase inhibitor tazobactam
For pseudomonas cover
Similar spectrum as imipenem/meropenem
Tigecyclin
Bacteria
Classification

Shape
1.
2.
3.
4.
5.
6.
Cocci
Bacilli
Vibrios - comma shaped organisms
Spirilla - spiral rods that don't bend
Spirochetes - spiral rods that bend in the middle
Actinomycetes - complex branching dos

Gram Stain
1. Positive
2. Negative

Ziehl-Neelsen stain: for mycobacterium (which possess a waxy coat and don't
stain)
Pathological Effects




Proliferate in tissues
Resist phagocytosis in somce cases
Secrete exotoxins and release endotoxins
Attach to cell membranes and damage them
Anaerobic organisms
Classification


Obligate anaerobes: grow only in absence of oxygen
Facultative anaerobe: grows in presence or absence of oxygen
Gram positive Gram Negative
Cocci Clostridium
Bacilli
Bacteroides
Fusobacterium
Actinomycosis
Actinomyces organsisms



Actinomyces israelii - Gram positive filamentous bacetrium
Commensal of alimentary tract - tonsils, mouth, upper intestine
Pathogenic when
1. Immunocompromised - Drugs, diabetes, steroids, AIDS, neoplasia
2. Mucosal damage - appendicits, perforation, radiotherapy
Diseases


Infection of neck, thorax, abdomen
May mimic malignancy
Diagnosis


Index of suspicion
Microscopy - "sulphur granules" / tissue histology
Clostridia
Characteristics of Clostridia :Positive - Spore - Endotoxic - Anaerobic Saphrophtyic
1. Gram positive
2. Spore forming
o Subterminal
o Drumstick
3. Exotoxin producing
o Botulinum - causes spastic paralysis with release of botulinum toxin
(inhibits acetylcholine release) opisthotonus + involvement of
respiratory muscles
o Perfringens (welchii) - proteolytic enzyme lecithinase causes gas
production - gas gangrene (with characteristic smell)
o Tetani - produces tetanospasmin (inhibits inhibitory processes of motor
neurones) causing muscular spasm and paralysis; prevented by tetanus
toxoid immunisation / human anti-tetanus immunoglobulin
o Difficile - exotoxin produces cell membrane damage to epithelial cells
leading to pseudomembranous colitis
4. Anaerobic
o Oxygen forms free radicals
o Cells have little/no defence
5. Saphrophytes - requires soil to protect them from dehydration
Helicobacter pylori
Classification




Curved/spiral gram negative bacterium
Present in gastric mucus in crypts and on the surface of gastric acid and
duodenal biopsies
More prevalent in the antrum than in the body of the stomach
Microaerophilic, flourishing best in low oxygen and high CO2 / H2
atmospheres
Disease associations
1.
2.
3.
4.
5.
Gastric erosion and gastric ulcer
Duodenal erosion and ulceration
Chronic gastritis
Gastric lymphoma of mucosa-associated lymphoid tissue
Gastric adenocarcinoma
Diagnostic tests
1. Gastric biopsy
o Culture
o Histology with modified Giemsa statin for helicobacter-like organisms
o Urease test on a biopsy specimen in agar gel with indicator system
o Urease test on biopsy specimen using detector strip that incorporates
the indicator system
2. Urease breath test
o Radio-labelled 13C or 14C given by mouth and measuring the amount of
radioactivity in the breath as a consequence of splitting of Urea
3. Serum test
o For H.pylori antibodies
Mycobacteria
Classification


Alcohol acid-fast bacilli
Would be gram positive if Gram stain could penetrate walls
1. Typical mycobacteria
o Mycobacterium Tuberculosis
o Mycobacterium leprae
2. Atypical mycobacteria
Resistant to standard antituberculosis drugs, different culture characteristics
from MTB (eg pigment production, different growth rate in culture)
o Mycobacterium avium intracellulare: - infection in AIDS
o Mycobacterium marinum: - swimming pool granuloma
o Mycobacterium ulcerans: - causes Buruli ulcer
o Mycobacterium kansasii: - chronic pulmonary infection
Mycobacterium Tuberculosis
Clinical classification
1. Primary TB: usually symptomless
o Lung - primary focus is "Ghon focus" with involvement of lymphatics
and enlargement of hilar lymph nodes. Ghon focus forms at periphery
of lung in mid-zone on a chest X-ray
o Tonsils with cervical lymph node involvement "scrofula"
o Terminal ileum with mesenteric lymph node involvement "tabes
mesenterica"
2. Post-primary TB: cough, fever, weight loss. Spread of infection limited by
severe local response with cavitation and fibrosis
o Haematogenous spread: miliary TB in many organs, TB meningitis,
bone/joint TB, renal TB
o Spread by rupture into air spaces - TB bronchopneumonia
Staphyloccoci and streptococci
Species
Main type
Staphylococci
Streptococci
 Gram positive cocci arranged
 Gram positive cocci
in clusters (hence "cocci")
arranged in chains or
 Form colonies - golden, white
pairs
colonies
 Transparent colonies
 Type by bacteriophage
 Typed by API strips
(bacterium-specific virus)
Classification By presence of absence of coagulase By type of haemolysis on culture
on blood-agar plate
1. Coagulase positive
o Staph aureus
1. Partial haemolysis 2. Coagulase negative
alpha: strep pneumoniae
o Staph epidermidis
2. Complete haemolysis o Staph saprophyticus
Beta: strep pyogenes
(causes erysipelas/nec
fasc)
3. No haemolysis - Gamma:
enterococci
By Lancefield group antigens





Group A: Strep pyogenes
Group B: none (strep
agalactiae)
Group C: none (strep
equisimilis)
Group D: enterococcus
faecalis
Group F: Viridans group
Treponemal diseases
Motile spiral organisms (spirochetes) - flex in middle as they move
Classification
1. Veneral
o T.pallidum pallidum - syphilis
2. Non veneral
o T.pallidum pertenue - yaws
o T.pallidum endemicum - bejel
o T.pallidum carateum - pinta
Culture Media
Solid - Isolation of separate colonies (esp when mixed growths)
Liquid - grow some sensitive organisms using enrichment broths
Exotoxins and Endotoxins
Exotoxin
Immunogenic protein secreted from
Definition a living organism (that is heat labile
and has a specific molecular target
Examples



Enzymes: vibrio
Neurotoxins: clostridium
Disrupters of membranes:
clostridium
Endotoxin
Lipopolysaccharide derived from the
cell wall of an organism that is not
usually immunogenic (is heat stable)
Cause





Cytokine formation
Fibrin degredation
Activation of clotting cascade
Kinin formation
Nitric oxide formation



Diseases





Cholera (vibrio)
Dipheri
Gas gangrene: cl.perfringens
Food poisioning
Botulism

Prostaglanding formation
Complement activation
Platelet activating factor
formation
Leucotriene formation





Shock
DIC
Hypotension
Organ failure
Pyrexia
Fungi
Fungi are larger than bacteria
Have nuclei with multiple chromosomes and cytoplasm containing mitochondria and
ribosomes
Can reproduce sexually by meiosis
Pathological by (1) infection - superficial, subcutaneous, systemic (2) toxin
production (3) hypersensitivity reactions
Predisposition - Immunocompromise; premature, AIDS, indwelling lines
Classification



Yeasts
Filamentous fungi
Dimorphic fungi
Candida



Commonest human pathogen is candida albicans sp
Affects mucous membranes (vagina, cervix, oropharynx), skin, respiratory
tract, urinary tract
Risk:
1. Diabetes
2. Immunocompromised
1. Acquired: drugs (steroids, cytotoxics), AIDS, leukaemia
2. Congenital

Diagnosis: (1) Microscopy (2) Culture (3) Antigen detection in urine, blood
(4) Antibody detection (5) Increased arabinitol - a metabolite of candida in
serum
Pathogenic fungi







Cryptococcus neoformans
Malassezia furfur
Dematophytes
Toulosis glabrata
Aspergillus fumigatus
Microsporum audouinii
Pneumocystis carinii
Viruses
Classification
1. RNA / DNA
o RNA: Influenzae, HIV, Rubella
o DNA: HSV, HPV, HIV
2. Size: parvovirus, picornavirus
3. Shape: rhabdovirus, small round virus
4. Tissue - Adeno (glandular), enterovirus
Neoplastic viruses
1. Directly cause neoplasia
o EBV: Burkitt's lymphoma (8:14), Nasopharyngeal carcinoma
o HPV: Cervical carcinoma
2. Predispose to neoplasia
o Chronic hepatitis: hepatocellular carcinoma
o AIDS: Lymphoma
3.Musculoskeletal
Osteoarthritis
Degenerative joint disease
Causes
1. Metabolic joint disease
o Abnormal lipid handling
o
o
o
o
Inherited hypercholesterolaemia and related disroders
Gout
Pyrophosphate arthropathies
Diabetes mellitus
2. Inflammatory joint disease
o Infective arthritis - gonococcus, salmonella
o Non-infective: RA, ank spond, psoriatic
3. Trauma
o Joint trauma
o Repetitive strain
4. Congenital
o Achondroplasia
Joints affected





Hip
Knee
Shoulder
Elbow
TMJ
Osteomyelitis
Osteomyelitis
Inflammation of bone and bone marrow
Causes
1. Infective
o Bacteria - staph aureus, ecoli, streptococci, bowel organisms
o Viruses
o Fungi
o Parasites
2. Non-infective
o Radiotherapy
Pathological Sequlae
1. Suppuration with pus in marrow cavity
2. Sequestrum: dead bone within periosteum that forms inner part of infected
bone marrow
3. Involucrum: reaction of periosteum to form new bone that 'envelops' the
infected site and contains it
4. Cloacae "sewer": holes in the involucrum through which pus formed in the
medulla discharges
5. Sinus: drainage tract from the cloaca to skin
6. Septicaemia and pyaemia
Late complications
1.
2.
3.
4.
Amyloidosis
Malignant change in the sinus - Marjolin's ulcer
Septicaemia and pyaemia
Suppurative arthritis
Pathological Fractures
Pathological Fracture
Fracture through previously abnormal bone
Causes
1.
2.
3.
4.
5.
Osteoporosis
Metabolic bone disease
Radiotherapy
Primary neoplasia
Paget's disease of bone
Oncology
Apoptosis
Apoptosis



Programmed cell death
Energy dependent process, requires specific protein synthesis (p53.Chr17).
Does not stimulate inflammatory response
May be physiological or pathological
Physiological
Pathological




Embryology: finger development,
development gut lumens
Thymus: physiological degeneration
Endometrial cycle
Menopause



Following cellular damage:
virus, bacteria, RT, drugs
Reaction to normal cell cycle
In response to tumours
Apoptosis Genes
Promotors
Un promotors
p53 - Chromosome 17 bcl-2
c-myc
BrCA1/2
Carcinogenesis
Carcinogenesis
1. Remote carcinogen
o Precursor of carcinogenic agent
2. Proximate carcinogen
o Metabolite of remote carcinogen with potential
o Needs further modification into ultimate
3. Ultimate carcinogen
o DNA interaction causes cancer
B-naphthylamine - ingested and absorbed from small bowel, metabolised in liver,
made soluble, excreted by kidney and causes cancer in bladder (after being
gluconurated by bladder epithelium).
Initiator: Alters DNA making it abnormal
Promoter: Leads to altered gene expression (eg hormones)
Cell cycle
Cell tissue classification in terms of ability to regenerate
1. Labile cells: - Bone marrow, testis, small, bowel (all contain stem cells)
2. Stable cells: liver, kidney, adrenal, bone
3. Permanent cells: CNS, skeletal muscle




G1: Gap phase.
Variation by lenght of cell's cycle is determined mostly by the lenght of time it
spends in G1
Retinoblastoma gene (Rb1) serves as restriction point (for cyclin dependent
kinase)
p53 gene produces p53 protein which arrests cell cycle by increasing
concentration of p31 (cyclin-dependent kinase inhibitor)
G0 - resting phase
S: Synthesis phase
Cell wall, cytoplasm, nuclear proteins made
G2: Second gap phase
M: Mitosis
Oncogene
Abberant genes which were previously important in the regulation of the cell cycle
Mechanisms of oncogenesis
1. Amplification: increases copies of proto-oncogene result in excessive activity
2. Point mutation: conversion of proto-oncogene into permanently active gene
3. Incorporation of new promoter: viruses can insert promotor sequences into
human DNA
4. Incorpation of enhancers
5. Translocation of chromosomal material
Mechanisms of action
1.
2.
3.
4.
Signal transduction pathway effects
Regulation of nuclear activity
Growth factors / receptors
Inhibition of apoptosis
Promotor
Inhibitor
Cyclin
p53, p27, p21
Cyclin-dependent Kinases
Rb - restriction
Epidermal growth factor (EGF) / c-erbB-2 BrCA1, BrCA2
PDGF / c-sis
APC gene
Insulin-like growth factor-1
Wilm's tumour gene
Transforming growth factor B
Interferon-alpha
Prostaglandin E2
Heparin
Chromosomal abnormalities
Normal chromosomal arrangement


Normal cells: 44 autosomes + 2 sex chromosomes
0,23,46, 46(n) - normal number of chromosomes in a cell (eg. RBC has none, striated
muscle 46n)
0
23
46
46n
Erythrocytes
Haploid cells
Gonads - sperm,
oocytes
Normal cells
Tetraploid - before
division
Multinucleated cells osteoclasts,
syncitiotrophoblasts,
muscle cells
Classification Chromosome abnormalities
Autosome
Sex chromosome
Structure


Translocations - one part onto another
Delections - loss of material
Number

Monosomy - loss of one pair of chromosomes
1. Turners XO
Trisomy - increase to three of one type of chromosom
1. Downs Chromosome 23
2. Edwards
3. Patau
Polyploidy - extra sets of entire chromosomes
1. Kleinfelter's


Location
Autosomal dominant
Autosomal recessive
X-linked

Single copy of gene
responsible for
disease

Both copies of
abnormal gene must
be present

Disease due to
abnormality on Xchromosome





FAP
APKD
Achondroplasia
Marfan's (fibrillin)
Spherocytosis
(spectrin)

Cystic fibrosis (7q
CFTR)
Alpha-1-Anti-trypsin
deficiency




Haemophilia A/B
G6PD
Fragile X
Red-green colour
blindness
Red-green colour
blindess (1/10)


Down's syndrome
Chromosomal abnormality
Three copies of chromosome 21
1. Non-disjunction (esp mothers > 40 years)
o Non-disjunction of a gamete: one progeny gets TWO chromosomes
(and the other one gets none) which is then fertilised by a normal
gamete from the other parent enduing up with THREE copies of
chromosomes.
o Usually maternally derived extra copy
2. Translocation (rare)
o Parents phenotypically normal but have a balanced translocation
o Chr 23 +Chr 23 / Ab Cr 22; get's one Chr 23 from mum, one Chr23
from dad and AbCr22+Down's shit
3. Mosaism
o 1/100 cases
o Normal ovum
o Non-disjunction after the blastocysts starts to develop
Associations



Congenital heart defects: PDA, VSD, ASD
Neoplasia
Increased incidence glue ear
Kleinfelter's syndrome
XXY - Extra X chromosome
Phenotypic features




Tall stature
Small genitalia
Gynaecomastia (same risk of breast cancer as women)
Female distribution of hair
Turner's syndrome
XO
Associations







Coarctation of the aorta
Webbing of neck
Wide carrying angle
Shield chest
Short stature
Streak ovaries
No learning difficulties
NB - normal X chromosome is inactivated by lyonisation. Lyonisation is incomplete
inactivation of X chromosomes.
Dysplasia
Dysplasia


A degree of failure of maturation of a tissue associated with a tendency to
aneuploidy and pleomorphism but without the capacity to spread
An abnormality of development of tissue in which fibrous or other non-specialised
tissue is present instead of the expected tissue
Causes of dysplasia
1. Chemicals
o Smoking
o Alcohol (larynx, stomach)
2. Viruses
o HPV 16,18
3. Specific chronic inflammation
o UC
4. Non-specific chronic inflammation
o Cystitis leading to bladder carcinoma
Sites of Dysplasia
1. Respiratory tract
o Bronchus: in relation to smoking
2. Gastrointestinal tract
o Oesophagus - in relation to candidiasis or other chronic irritation with
results in squamous dysplasia
o Oesophagus: Barrett's oesophagus - glandular dysplasia
o Stomach: H.pylori infection
o Large bowel: ulcerative colitis
3. Urogenital tract
o Cervix: CIN
Histological featurs
1.
2.
3.
4.
5.
6.
Multilayering (of a columnar or cuboidal) epithelium
Mitotic figures - increased in number, presence of abnormal mitoses
Pleomorphism
Hyperchromatism
Loss of cell-cell adhesion resulting in shedding
No invasion of basement membrane
‹
Effects of tumours
Cachexia (IL1, TNFa related)
Primary / Local effects







Pressure effects
Obstruction/compression
Haemorrhage
Infection leading to septicaemia
Infarction (torsion of polyp)
Pathological fractures
Biochemical/hormonal abnormalities
Metastatic effects
Paraneoplastic manifestations

Syndrome in which there are symptoms and signs caused by a neoplasm other
than by its direct involvement, metastatic spread
Classification
1. Endocrine
o Cushing's syndrome
o ADH secretion
o PTHrP
o Carcinoid syndrome
2. Haematological
o Polycythaemia
o DIC
o Thrombocythaemia
3. Dermatological
o Acanthosis nigricans
o Dermatomyositis
o Erythema gyratum repens
o Erythroderma
o Clubbing
4. Neuromuscular
o Polymyositis
o Myopathies - Myasthenia, GBS
Hormones & Neoplasia
Relationships with neoplasia
1. Hormones cause neoplasms
o Tamoxifen: endometrial adenocarcinoma (partial oestrogen agonist)
o Oestrogen causes endometrial cancer
o Methylated steroid hormones cause liver neoplasms
2. Hormones treat neoplasms
o Tamoxifen + breast
o Progestogens + endometrial cancer
o Antiandrogens + prostate cancer
o Thyroid cancer with thyroxine
3. Neoplasms secrete hormones
o Eutopic (from tumour tissues that normally secrete hormones) adrenal, ovarian, thyroid, pituitary, kidney
o Ectopic (from tissues that do not normally secrete hormoneS) carcinoid, neuroendocrine tumours
4. Neoplasms may be hormone dependent
o Papillary carcinoma of thyroid
o Breast ca may be dependent on oestrogen
Nomenclature
Carcinoma
Malignant tumour of epithelial cells
1.
2.
3.
4.
Squamous epithelium - SCC, melanoma, hepatocellular carcinoma
Glandular epithelium - Adenocarcinoma
Transitional epithelium (urinary tract)
Undifferentiated (anaplastic)
Sarcoma
Malignant tumour composed of connective tissue cells (mesenchyme)
1.
2.
3.
4.
Ligament - chondrosarcoma
Fat - liposarcoma
Bone - osteosarcoma
Fibrous tissue - fibrosarcoma
Typed by tissue that forms the greatest volumne of the tumour
Blastoma
Characteristically childhood tumours
Eg. Retinoblastoma, nephroblastom (Wilm's tumour), Neuroblastoma,
Medulloblastoma, Hepatoblastoma
Teratoma
Neoplasm composed of cells with potential to form all three germ layers.
May benign or malignant
99% ovary benign, 99% testicular malignant
Grading




Well differentiated
Moderately differentiated
Poorly differentiated
Undifferentiated
Examples:
1. Rye classification of lymphoma
2. Bloom & Richardson grading system
Staging
Degree of spread
Examples:
1.
2.
3.
4.
Royal Marsden Testicular cancer
Ann-Arbor Lymphoma
Duke's staging of colorectal cancer
Breast Manchester / Columbia system
Testicular cancer
Classification
1. Primary 95%
o Germ cell (seminoma, teratoma)
o Non-germ cell
2. Secondary 5%
o Lymphoma
o Metastatic (lymphoma, leukaemia, melanoma)
Risk factors
1.
2.
3.
4.
5.
Testicular maldescent (1/20 have malignancy)
Mumps orchitis
Trauma
Maternal oestrogen exposure
Genetics: 12p chromosomal abnormalities
Royal Marsden Hospital Staging system





I: Confined to testis
II: Confined to testis but with persistently raised tumour markers
III: Infradiaphragmatic node involvement
IV: both sides of diaphragm
V: Extralymphatic metastases
Management
1. History
o
o
Risk factors - trauma, mumps, maledescent, maternal oestrogen
Genetics
2. Examination
o Regional nodes - drain to para-aortic
3. Investigations
o Blood tests: Tumour marker assay, aFP, LDH, HhcG
o CXR: Pulmonary metastases
o USS scrotum
o Chest / abdominal CT - detection of metastases in retroperitoneum and
mediastinum
4. Treatment
o Scrotal exploration: if diagnosis is uncertain; scrotum can be explored and
possible tumour biopsy
o Orchidectomy: if there is any doubt
o Radiotherapy (seminomas highly radiosensitive)
o Chemotherapy for advanced stage disease
Radiation
Classification
1. Electromagnetic
1. Infra-red
2. Ultraviolet
3. X-ray
4. Gamma-ray
5. cosmic rays
2. Particulate
1. alpha particles (electron)
2. beta particles(hydrogen nucleus)
Cellular damage mechanisms


Direct DNA damage (TT dimers, base deletions, cross linkages)
Indirect damage to proteins, membranes, enzymes (via free radicals - unpaired
electron)
Rad
Effect
100,000 Death in minutes (nuclear bomb)
10,000 Death within hours from CNS effects
1000
100
Death in weeks from pancytopenia
Nausea & vomiting
Radiation sensitivity is not commensurate with a tissues capacity to regenerate.
Radiosensitive (radidly
Intermediate
growing)
Bone marrow
Gonads
Growing cartilage/bone
Lens of eye (risk from UV)
Bowel
Thyroid
Pituitary
Kidney
Heart
Lung
Liver
Brain
Skin (risk from UV)
Resistant
Tumour Markers
Tumour Marker
1. Substance found in circulation (or immunohistochemical marker)
2. Directly related to presence of neoplasm
3. Disappears when neoplasm treated, reappears when neoplasm recurs
Not usually stoichiometric - not in direct proportion to tumour bulk
Classification
1. Hormones: Eutopical / ectopical
o ACTH
o hGH (pituitary adenoma)
o EPO - renal cell carcinoma
o B-hCG: teratomas, choriocarcinoma
2. Enzymes
o Prostatic acic phosphatase (not prostatic specific antigen) - Ca prostate
o Placental alkaline phosphatase - ca bronchus, pancreas, colon
3. Oncofetal antigens
o a-fetoprotein (foetal albumin): germ cell tumours, hepatocellular
carcinoma
o
Carcioembryonic antigen (CEA): colorectal
4.Urological
Renal cell carcinoma
Presenting features
1. General / primary
o Weight loss, cachexia
o Mass in loin
o New varicocoele on left (as left gonadal vein is longer and thus more
easily compressed)
2. Secondary
3. Paraneoplastic manifestations
Investigations




Urine dipstick
FBC, LFTs
Imaging: USS / CT
CXR: cannonball pulmonary metastases
Rhabdomyolysis
Rhabdomyolysis
Clinical syndrome caused by release of potentially toxic muscle cell components into
circulation
Triggers
1. Trauma
o
o
o
o
Crush injury
Burns
Hypothermia
Reperfusion
2. Drugs
3. Congenital
Complications
1.
2.
3.
4.
Renal failure - ischaemic tubular injury
DIC
Compartment syndrome
Electrolyte imbalances - hyperkalaemia, hypocalcaemia, hyperphosphataemia,
hyperuricaemia
5. Hypovolaemia
Diagnosis
1.
2.
3.
4.
Elevated CK (x5 normal)
Elevated creatinine
Elevated serum lactate dehydrogenase
Dark urine + positive urine dipstick
Management
1.
2.
3.
4.
Adequate hydration
Diuretics
Alkalinise urine
Manage electrolyte disturbances
Epistaxis
The Nose
1. Bony and cartilaginous framework
2. Overlied by skin and fibrofatty tissue
3. Bones:
o external: nasal bone + frontal process maxilla
o Internal: nasal, frontal (crista galli), ethmoid, maxillary (palatine
process), sphenoidal
o Medial septum: vomer, ethmoid perpendicular plate
4. Divided into left and right nasal cavities by nasal septum (perpendicular plate
of ethmoid bone)
5. Epithelium: respiratory (ciliated columnar)
6. Conchae/meatus/turbinates
o Superior meatus: opening of posterior ethmoidal air cells
o Middle meatus: frontal, maxillary, anterior and middle ethmoidal
o Inferior meatus: nasolacrimal duct from eye
Blood Supply to the nose
(All derived from external carotid artery)
1.
2.
3.
4.
5.
Anterior ethmoidal
Posterior ethmoidal
Sphenopalatine
Greater palatine
External branches of labial
Epistaxis
Management
1. Resuscitate
2. History
o Duration of bleeding
o Preceding injuries: nose picking, nasal trauma, infection, neoplasia
o Medications - anticoagulants, antiplatelet agents
o PMHx of bleeding diathesis, family history
o Perpetuating factors - hypertension
3. Assess bleeding
o FBC, U/Es, LFTs, Coag
4. Examination (personal protection - gown/apron/gloves/visor)
o Patient should attempt to clear their nose
o Spray local anaesthetic (with adrenaline as vasoconstrictor)
o Identify source of bleeding by anterior rhinoscopy with Thudicum's
speculum
o Look at kisselbach's plexus (anterior part of septum in Little's area)
o
If bleeding not visible, may be posterior bleed
5. Emergency Treatment
o Digital pressure to entire nose + cold compress/ice pack
o Silver nitrate cautery / electrocautery coagulation of vessel (only one
side of septum should be cauterised at once; small risk of septal
perforation)
o Pack nostril with nasal tampon (Merocel) / ribbon gauze (BIPP) - can
pack both to increase tamponade effect; complications - sinusitism,
airway obstruction, inhalation of pack, infection (risk of toxic shock
syndrome)
o Foley balloon catheter used for tamponade
6. Surgical treatment
o Posterior nasal packing (under GA)
o Submucosal resection which decreases blood flow to mucosa
o Endoscopic visualisation of sphenopalatine artery and bipolar cautery/
ligation
o Arterial ligation
o Angiogram and embolisation
7. Follow up
o BP check with GP
o Further nasal examination to exclude neoplasia