General Pathology

Pathology

General Pathology

Abscess and Pus

Pus

Composed of two phases

1. Solid:

o live/dead polymorphs, macrophages

o Bacteria/causative agent (eg irritant chemicals)

o 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 / 1.
AA / Secondary/Reactive amyloid
From chronic conditions - macrophages secrete ILs that stimulate hepatocytes to secrete serum amyloid 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 / 1.
AH/AB / Occurs with Alzheimer's disease with APP as precursor

Anaemia

Red cell precursors

· Myeloblasts

· Myelocytes

· Early normoblasts

· Late normoblasts

· Reticulocytes

Anaemia

Microcytic / Normocytic / Macrocytic
1. Iron deficiency anaemia / 1. Haemolytic
2. Anaemia of chronic disease / 1. B12 (3 year stores in liver - functions as 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 usuallyfound in the body, present in BM and occasionallyfound in peripheral blood

1. B12

o Functions as co-enzyme to produce methionine from tetrahydrofolate

o 3 years store

o Deficiency in (1) Pernicious anaemia GPC antibodies (2) partial/total gastrectomy (3) failure to absorp from terminal ileum

2. Folate

o Tetrahydrofolate used to form methionine from homocysteine

o 3 months store in liver

o Deficiency (1) inadequate intakeor 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

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 / · Polysegmented nuclei (hypersegmented in B12/folate deficiency)
· Clear cytoplasm with fine granules (contain elastase, protease, A1AT, lysosyme, lactoferrin)
· Close relation with acute inflammation
Basophils / · Unlobulated or bilobate nuclei
· Granules contain histamine, eosinophil chemotactic factor, slow-releasing substance of anaphylaxis
· Close relation with allergic reactions/anaphylaxis
Eosinophils / · 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 Megakaryocytes

o Skeletal muscle cells

o 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

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

· Abnormal mass of precipitated solid material in a duct

1. Prostatic (commonest: most TURP and prostatectomy specimens have calculi)

2. Biliary

3. Urinary

4. Pancreatic

5. 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 / Organisms / Management
Cellulitis / Infection of the skin and underlying subcutaneous tissues / · Staph aureus / epidermidis
· Streptoocci / History
Swab
IV antibiotics - benpen/fluclox or clindamycin/erythromycin (if penicillin allergic)
Erysipelas / A form of cellulitis
Occurs in immunocompromised, young, old / · Lancefield A B-haemolytic streptococci
Necrotising fascitits / Necrotising process of the deep fascia
Forms
· Fournier's gangrene (of the scrotum) / · Lancefield A B-haemolytic streptococci / Resuscitation
Blood cultures / wound swab
Antibiotics
Radical tissue debridement

Complement Cascade

The Complement system

· Important mechanism to control infection

· Promotes phagocytosis

· Involved in bactericidal mechanisms

· Promotes lymphocyte function

· Mediates inflammation through mast cell degranulation and chemotaxis

Classical pathway / Alternate 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 / · C3 activated directly by endotoxins, viruses, bacteria, fungi
· Does not need immunoglobulin activation

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

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

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

· 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 Circulation system: arterio-venous fistula, AAAs

o 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 Persisting cause / material

o Persisting sepsis

o Persisting flow through fistula

o Width of fistula

o Ischaemia

o Epidermidisation of track

o 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 Remove cause

o Drain abscess cavities

o Avoid antibiotics

o 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

Haemoglobinopathy / Pathology / Blood picture / Complications
Sickle cell disease / Single amino acid substitution on B-chain at position 6 of valine for glutamic acid
· Autosomal co-dominant: homozygotes have 90-100% HbS, heterozygotes have 20-40% / · Normochromic
· Microcytic anaemia
· Sickled cells
· Reticulocytosis
· Features of splenic atrophy (target cells, acanthocytes, Howell-Jolly bodies) / · Haemolytic anaemia results in cardiac failure
· Pigment gallstones
· Thrombosis and infarction - abdomen, chest, splene, bone
· Infection - salmonella osteomyelitis, pneumococcal sepsis
Thalassaemia / Defective globin chain synthesis - causes abnormal haemoglobin production
· Alpha Thalassaemia - China, Asia, Africa
· Beta Thalassaemia - Mediterranean, Middle East / · 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, thrombocytopenia

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. Haemangiomas

2. Peutz-Jegher's polyp of bowel

3. Bronchial hamartoma

4. Melanocytic naevi

5. Neurofibromatosis

6. Tuberous Sclerosis

Morbidity from Hamartoma

1. Obstruction

2. Pressure

3. Infection

4. Infarction

5. Haemorrhage

6. Fracture

Hernia

· Protusion of a viscus or tissue from the body compartment in which it normally resides into another body compartment