pathology everything

what is pathology?

the study of disease by scientific means, elucidating its causes and effects

branch of medical science that investigates the causes, nature and effects of diseases - plays a crucial role in advancing our understanding of diseases, improving diagnostic accuracy, and facilitating personalised patient care

pathos = disease

logos = discourse

what does pathology involve?

• study of abnormal changes in cells, tissues, organs and bodily fluids, aiming to understand the underlying mechanisms of disease processes

• analysis of specimens collected through biopsies, surgeries or autopsies to diagnose diseases, determine their progression, and guide treatment decisions

• use of various techniques, including micropsy, molecular testing and imaging, to identify cellular, molecular and gross abnormalities and provide insights into disease development and management.

what is the definition of diagnosis?

determination of the exact nature of disease

what is a biopsy?

sample of body tissue during life to aid in diagnosis

what is an autopsy?

aka necropsy, examination of body/organs after death to aid in determination of the cause of death

what is anatomical pathology and the two disciplines of anatomical pathology?

detecting structural abnormalities in tissues and cells

naked eye/microscopic examination of biopsy/autopsy material

excision/surgical specimens → histopathology

exfoliative/needle specimens → cytology

what is the pathology discipline histopathology/histology?

• excision/surgical specimens → histopathology

  • cutting a piece of tissue out

  • ie. suspicious mole

• assessing microscopic anatomy of tissue - what is one cell doing to the other tissue?

• is the abnormal tissue doing to the normal tissue?

what is the pathology discipline cytology/cytopathology?

• exfoliative/needle specimens → cytology

  • scrapings of tissue cells

  • ie. cervix

• looking at cells

what is exfoliative biopsy as an example of cytology?

• examination of secretions, tissue scraping for detection of cancerous cells

  • ie. cervix, lung, stomach, bladder cancers

what is fine needle aspiration as an example of cytology?

• extracting cells from a suspected mass

  • ie. breast, lymph node, thyroid

what is the pathology discipline haematology?

• detection of blood and bone marrow abnormalities

• red blood cell, white blood cell, platelet disorders

• anomalies in blood cell profile: number, size, shape, structure

• clotting diseases and effects of other diseases on the blood

• cross matching blood for compatible transfusions

what is the pathology discipline biochemistry?

• detection of abnormalities in body chemistry

• metabolism analysed for disease (ie. levels of glucose, urea, electrolytes, enzymes, hormones)

• analysis of blood, urine, CSF other bodily fluids

• protein (albumin → oedema), lipid (cholesterol → heart disease, atherosclerosis), carbohydrate (glucose → diabetes) levels

• blood or urine testing, cerebrospinal fluid

what is the pathology discipline microbiology?

• detection of infectious disease

• analysis of blood, urine, faeces, secretions (vaginal, genital)

• respiratory swabs for diagnosis of COVID

• bacteria, virus, fungi, parasites, sample of normal flora or exogenous acquired infections from environment, animal sources

• HIV → AIDS

• SARS COV 2 → COVID 19

• virus causes illness

what is the pathology discipline immunoserology?

• can be considered subdivision of microbiology

• detection of immune disease/status and infectious disease

• detecting HIV positive

• analysis of blood and other bodily fluids for antigen/antibody reactions

• ELISA test

what is the pathology discipline molecular pathology?

• can be under biochemistry, microbiology, cytopathology (HPV)

• detection of abnormalities at molecular level (gene and gene products)

• analysis of very small amounts of tissues and bodily fluids

• PCR (polymerase chain reaction) machine, amplifying genetic material/DNA/nucleic acids

• checking for viral DNA sequences

• infection unable to detect via blood/urine/culture → chlamydia, gonorrhoea

what is the pathology discipline medical genetics?

• detection of inherited disease

• prenatal diagnosis

  • amniocentesis (amniotic fluid containing foetal cells), chorionic villus sampling (placenta)

• chromosome spread karyotype

what is the discipline medical radiations (radiography, nuclear medicine, radiation therapy)?

• not considered a pathology discipline

• aids in diagnosis and/or treatment of disease

• x radiation

• computed tomography

• magnetic resonance imaging

• ultrasound

• SPECT, PET, nuclear medicine scans

• provides details in abnormalities regarding structures of the body

• detecting changes in function of body

what are symptoms?

complaints that the patient is aware of

weakness, pain, fever, headache, SOB

what are signs?

abnormalities associated with a disease that the patient is not usually aware of

retinal bleeding caused by high blood pressure

crackling lung sounds, heart sounds0

what is a differential diagnosis?

clinician lists possible diseases that may cause the symptoms and signs

what is a presumptive diagnosis?

• an initial diagnosis is made

• assumed most likely diagnosis for the patient

• the most likely diagnosis

• tests still required to rule out other differential diagnoses

what is a definitive diagnosis?

following test results, a final diagnosis is made

after ruling out all other differential diagnoses

what is a prognosis?

a forecast is made on the probable course and outcome of the disease

what is remission?

• state of absence of disease activity in patients with a chronic illness, with the possibility of return

• after cancer has been removed they are in remission

what is relapse?

• state of renewed disease activity following the end of a remission

• if cancer returns after remission, they have relapsed

how can disease can be classified and what do they mean? (2)

1. by an eponymous term

   • giving the disease the name of the discoverer

   • ie. Bright’s disease

2. by a descriptive term

   • ie. glomerulonephritis

     • related to the kidney at the glomerular level

   • provides more information to the name

what is the definition of aetiology?

the cause of a disease

ie. Staph. aureus causing bronchopneumonia

what is the definition of pathogenesis?

• how the aetiology brings about the disease

• the ‘course’ of the disease

how can diseases be grouped? (2)

1. genetically determined

2. acquired

what is a genetically determined disease?

• due to gene defects/DNA anomalies

• may be influenced by environment

• present at birth

• may be brought about by abnormal genes that are inherited, or by abnormal expression of normal genes

what are the types of genetically determined diseases? (4)

1. cytogenic disorders

2. Mendelian disorders

3. multifactorial inheritance disorders

4. congenital malformations

what is a cytogenic disorder of genetically determined disease?

• chromosomal defects (structure/number)

• down’s syndrome

  • 47 chromosomes/cell

  • 47, XY+21

• Klinefelter’s syndrome

  • 47, XXY - male but with feminised features

what is a Mendelian disorder of genetically determined disease?

• due to gene defects

• ie. Phenylketonuria (PKU)

  • enzyme gene defect leads to abnormal metabolism of phenylalanine

what is a multi factorial inheritance disorder of genetically determined disease?

• often involve many genes (polygenic)

• may have an environmental influence

• ie. hypertension

  • a set of genes predisposes one to hypertension

  • environmental factors (salt, stress) can contribute

what is a congenital malformation of genetically determined disease?

• DNA expression errors ie. heart defects

• may have an environmental cause

• ie. thalidomide phocomelia - morning sickness drug interfering with development of limbs

• ie. rubella virus infection of mother - causing deafness and blindness of baby

• gross anatomical defects

what is acquired disease?

due to environmental factors

due to environmental agents interacting with the tissues of the body and causing cell
injury.

more common than genetic diseases

what are the environmental factors that can contribute to acquired disease? (3)

• aetiology

  • causative agent

• predisposing factors

  • these make one more likely to develop the disease

  • ie. cigarette smoking

• contributing factors

  • make one develop the disease more severely

  • ie. malnutrition

what are the pathological stimuli that can cause acquired disease? (8)

1. physical agents

2. chemical agents

3. biological/infective agents

4. immune factors

5. deficiency or excess factors

6. psychogenic factors

7. iatrogenic factors

8. idiopathic factors

what are physical agents as a pathological stimuli that can cause acquired disease?

• trauma, heat, cold, radiation (X rays, UV rays)

what are chemical agents as a pathological stimuli that can cause acquired disease?

• synthetic, naturally occurring chemicals

• elements, compounds, toxins, poisons, free radicals

• acid burn: chemical damage to tissue

• alcohol damaging liver, cirrhosis, stomach lining, ulcers, fatty change

what are biological/infective agents as a pathological stimuli that can cause acquired disease?

• worms, protozoa, fungi, bacteria, viruses leading to variety of lesions

• respiratory, gastrointestinal, urinary, skin, genital infections

• facial herpes (viral infection)

what are immune factors as a pathological stimuli that can cause acquired disease?

• allergies/hypersensitivities, autoimmunity, immunodeficiency (ie. AIDS)

• exaggerated immune responses

• attacking self cells

• allergy (hypersensitivity reaction) to mosquito bite

what are deficiency or excess factors as a pathological stimuli that can cause acquired disease?

• deficiency or excess of vitamins, minerals, hormones, oxygen

• Kwashiorkor - severe dietary protein deficiency - changes in skin, hair

• excess oestrogen can lead to breast/uterine cancer

• excess testosterone can lead to prostate cancer

• decreased growth hormone - dwarfism

what are psychogenic factors as a pathological stimuli that can cause acquired disease?

• caused by or greatly contributed to by patient’s psychological state

• psychological factors acting as pathological stimuli

• chronic peptic ulcer

  • stress contributes to its pathogenesis

• chest pain, heart palpitations, high blood pressure

what are iatrogenic factors as a pathological stimuli that can cause acquired disease?

• caused by medical/paramedical intervention (maltreatment, wrong dosage)

• aspirin overdose → leads to haemorrhage

• penicillin when patient is allergic → anaphylaxis

what are idiopathic factors as a pathological stimuli that can cause acquired disease?

• of unknown cause

• may have multifactorial aetiology

• ie. sarcoidosis

• some brain tumours

what is injury, and how can it be categorised? (4)

• injury is any stress upon tissue or a cell that disrupts its normal structure and function

• sublethal or lethal, mild or severe

• this results in a pathological process in tissue, causing disease

• any stress that acts on the body and causes disruption to the normal physiological processes that
  are active in tissues. This results in an abnormal, pathological process that may disrupt normal anatomy
  and brings about disease

what is trauma?

• trauma is an injury due to mechanical/physical agent

  • not biological or chemical

  • trauma: physical disruption to tissue

what are parenchymal cells?

• parenchymal cells (specialised cells of the organ)

• parenchymal cells gives organ specific function

  • the heart, cardiocytes

  • the brain, neurons

what occurs to parenchymal cells during sublethal (mild) injury? (5)

sublethal (reactive changes)

1. hydropic change

2. fatty change

3. glycogen depletion

4. decreased protein synthesis

5. autophagy

what is hydropic change occurring to parenchymal cells during sublethal (mild) injury?

• membrane ion pumps failing

  • cells accumulate water and electrolytes - cloudy swelling

• there is still nuclei present - cells have not died

• reversible if stimulus is removed

what is fatty change occurring to parenchymal cells during sublethal (mild) injury?

• smooth endoplasmic reticulum damaged

• fat metabolism stops, cytoplasm accumulates fat droplets - signet ring

• nucleus pushed to the side - peripheral

• reversible

what is glycogen depletion occurring to parenchymal cells during sublethal (mild) injury?

• mitochondria damaged

• cells begin to produce more ATP anaerobically and demonstrate loss of glycogen - using glycogen stores

• periodic acid Schiff PAS staining method used to detect glycogen

• reversible

what is decreased protein synthesis occurring to parenchymal cells during sublethal (mild) injury?

• ribosomes, granular/rough endoplasmic reticulum damaged

• protein synthesis stops

• cytoplasm stains more eosinophilic (ie. more pink)

• reversible

what is autophagy occurring to parenchymal cells during sublethal (mild) injury?

• lysosomes damaged

• lytic enzymes released in pockets of cytoplasm

• vacuolation seen as a result of limited digestion of cytoplasm

• bubbles in cytoplasm

• reversible

what are connective tissue cells and what occurs to them during sublethal (mild) injury?

• connective tissue cells (supporting cells of the organ) → acute or chronic inflammation

  • macrophages, fat cells, adipose, nerve cells

what occurs to parenchymal and connective tissue cells during lethal (severe) injury?

necrosis

what is necrosis?

death of cells while still part of living body

what is hypoxia?

mild injury, deficiency in the amount of oxygen reaching the tissues, partial occlusion

can cause angina pectoris in myocardium

what is anoxia?

severe injury, an absence of oxygen, complete occlusion

can cause myocardial infarction (heart attack)

what is the aetiology of myocardial infarction?

ischaemia (interrupted blood supply) due to blockage of end artery to myocardium

what is the pathogenesis of myocardial infarction?

1. acute anoxia to tissue

2. oxidative phosphorylation stops

3. anaerobic glycolysis generates ATP

4. membrane ion pumps start to fail, influx of H2O and electrolytes, cell swells

5. biochemical necrosis (point of irreversibility)

6. intracellular membrane rupture

7. .

   a. autolysis: cytoplasm dissolves
   b. coagulation: cytoplasm solidifies

8. histological necrosis ~= 8 hours

what are the nuclear changes seen in the process of necrosis, and what happens? (3)

1. pyknosis: nucleus shrinks and condenses

2. karyorrhexis: nucleus fragments

3. karyolysis: nuclear fragments dissolve away

how can a patient react to necrotic tissue? (4)

• in vital organs such as heart (myocardial infarct), brain (stroke) → death may occur

• if patient survives

  1. inflammation seen around necrotic region and necrotic tissue removed by phagocytic cells

  2. necrotic tissue replaced by scar tissue (ie. fibrosis, except in the brain where gliosis occurs)

  3. calcium may deposit in necrotic tissues

     • dystrophic calcification, necrotic tissues only, normal blood calcium levels

     • metastatic calcification, both living and necrotic tissues, hypercalcaemia

what are the types of necrosis?

1. coagulative necrosis

2. colliquative (liquefactive) necrosis

   a. occurs in the brain
   b. occurs in suppuration (pus formation)

3. caseous necrosis

4. haemorrhagic necrosis

5. gummatous necrosis

6. fat necrosis

   a. enzymatic type
   b. traumatic type

7. fibrinoid necrosis

8. gangrenous necrosis

what is coagulative necrosis?

• most common, occurs in solid organs

  • ie. heart, kidney, spleen, liver

• due to ischaemia → coagulation of proteins (myocardial infarction)

what are the two types of colliquative (liquefactive) necrosis?

i. Occurs in the brain

• due to autolysis progressing almost to completion with little coagulation

• ischaemia → autolysis of cells (cerebral infarct - stroke)

ii. Occurs in suppuration (pus formation)

• due to neutrophils lysing pyogenic bacteria and tissue, ie. heterolysis (not autolysis, not self-lysis of cells)

• heterolysis of cells (abscess)

  • neutrophils lyse bacteria

what is caseous necrosis?

• occurs in tuberculosis (infection with Mycobacterium tuberculosis)

• due to type 4 hypersensitivity reaction and nature of bacterium

• caseous necrosis of lung

• appears like cottage cheese, very crumbly

what is haemorrhagic necrosis?

• result of ischaemia leading to necrotic tissue infiltrated with extravasated red blood cells

• ie. lung infarct with blood supply still present or torsion of the testis

• trickle of blood into infarcted area

what is gummatous necrosis?

• due to infection with Treponema pallidum

• occurs in tertiary syphilis

• especially in cardiovascular system and central nervous system

• causes gumma lesions

• variation of coagulative necrosis

what are the two types of fat necrosis?

i. Enzymatic type

• only occurs around pancreas

• associated with adipose tissue injury and release of pancreatic lipases (ie. in alcoholics)

ii. Traumatic type

• occurs when adipose tissue in any site is injured by trauma

• ie. injury to breast tissue following surgery

what is fibrinoid necrosis?

• occurs in connective tissue, blood vessel walls in hypertension and autoimmune disease

• collagen degenerates, resembles fibrin but not true fibrin

• fibrinoid nodule seen in rheumatoid arthritis

what is gangrenous necrosis?

• dark, discoloured, foul smelling tissue

• result of ischaemia (coagulative necrosis) and infection of necrotic tissue with anaerobic bacteria, especially Clostridium spp

what is apoptosis?

• shrinkage necrosis (no inflammation/other degenerative changes)

• a controlled process of cell death, programmed into cells to occur at a certain stage in their life cycle

• death inducing signals are more dominant than cell surviving signals

when can apoptosis occur? (5)

1. embryogenesis ie. in separating digits

2. withdrawal of a hormonal growth stimulus ie. uterus following childbirth

3. removal of cells with high turnover ie. gastric mucosal epithelial cells

4. removal of cells with acquired DNA damage ie. viral infection, irradiation, cytotoxic drugs

5. removal of neoplastic cells in tumours

what is disease?

any departure from the normal physiology and anatomy evident in a healthy body. Diseased
tissue will show abnormalities in its morphology (structure)

what is ischaemia?

lack of blood in a tissue (interrupted blood supply)

what is inflammation?

response of connective tissue to mild/sublethal injury, and may also be seen following necrosis

what are the potential processes of inflammation, and how long do they take? (3)

• process may be

  • acute

    • short lasting, hours to days

  • subacute

    • days to weeks

  • or chronic

    • long lasting, weeks, months, years

how are inflamed tissues named?

• inflamed tissues are named accordingly

  • prefix = tissue name in Latin or Greek

  • suffix = itis

  • tonsilitis, appendicitis, hepatitis

  • exceptions pneumonia, pleurisy (aka pleuritis)

what are the examples of respiratory inflammations? (8)

1. rhinitis - nose

2. bronchiolitis

3. sinusitis

4. tracheo-bronchitis

5. tracheitis - trachea

6. pneumonia - inflammation at alveolar level

7. laryngitis - larynx

8. pleurisy/pleuritis - pleura

what are the 5 cardinal signs of acute inflammation?

1. calor - heat

2. rubor - redness

3. dolor - pain

4. tumor - swelling

5. functio laesa - loss of function

what is the series of reactions in acute inflammation causing the cardinal signs?

1. transient vasoconstriction of arterioles → blanching of area (not always seen)

   • scratching a line into skin with nail produces white line

2. sustained vasodilation of arterioles/venules and hyperaemia (increased blood flow to area) → redness, heat

   • histamine released

3. increased vascular permeability

   • histamine helps cause vessels to be leaky

   • increased leakiness of vessels to fluid and protein, leading to formation of inflammatory exudate

   • → swelling, pain, loss of function

4. stasis (blood flow slows or stops)

5. margination and diapedesis

   • escape of leukocytes from circulation to tissue

   • adhere to white blood cell wall and then pass through into tissue space

6. chemotaxis

   • movement of leukocytes to site of injury

   • increased tissue pressure

   • → pain, loss of function

7. phagocytosis

   • ingestion of necrotic debris, toxins

what is histamine release in acute inflammation illustrated by? (3)

• pallor - vasoconstriction

• flare (redness) - vasodilation

• weal (swelling) - exudate

what are the types of escape of fluid from vessels? (3)

1. continuous

2. fenestrated

3. sinusoidal

what is continuous escape of fluid from vessels, and where is it seen?

• skin, muscle, CNS

  • endothelium have to open up for fluid to flow

what is fenestrated escape of fluid from vessels, and where is it seen?

• glands, kidneys, gastrointestinal system

  • areas that are thinner and thicker

  • fluid could seep through

what is sinusoidal escape of fluid from vessels, and where is it seen?

• seen in liver, spleen, bone marrow

  • easy to produce exudate

what are Starling forces, and what does it help form?

• physical forces acting across capillary walls (Starling forces) causes fluid to move from within vessels to extravascular space, and vice versa

• these forces determine how much fluid is lost to extravascular space

• transudate (tissue fluid) forms in normal tissue via Starling forces while lymphatics return fluid to circulation

what are the types of exudate? (4)

the composition of exudate depends on nature of injury

1. serous inflammatory exudate

2. fibrinous exudate

3. suppurative exudate

4. haemorrhagic exudate

between transudate, plasma and exudate, which has the highest concentration of protein?

normal plasma > exudate > transudate

plasma has the highest concentration

what is serous inflammatory exudate?

• low protein levels and very little leukocytic emigration

• very watery

• very few white blood cells move into tissue

• ie. skin blister

  • touching a very hot plate

what is fibrinous exudate?

• kidney disease

• high urea in blood

• high protein levels ie. fibrinous pericarditis or pleurisy

• high fibrinogen (soluble in circulation)

• high fibrin (insoluble and sticky in tissue)

• ie. pleural “friction rub”

• when clinician listens to lungs, they will hear friction rub

what is suppurative exudate?

• much leukocytic emigration due to infection

  • infection and leukocytes form pus

• ie. meningitis

what is haemorrhagic exudate?

• injury directly damages vessels and all blood components (fluid, proteins, RBC, WBC) leak out

• bacterial infection (Helicobacter pylori) → thrive in high acid → stomach

• ie. bleeding peptic ulcer

• looks red (RBC)

what are the factors controlling exudate formation? (5)

1. endogenous mediators will wear off

   • histamine

2. arterioles gradually constrict

3. platelets plug up leaking vessel

4. distensibility of tissue is limited

5. increased lymphatic drainage

what is the purpose of exudate in acute inflammation?

i. fluid

• water, electrolytes, dilutes toxins

ii. proteins

• antibodies important in immunity, inactivate microbes

• fibrin forms, acts as tissue glue

• fibrin pretends spread of bacteria in tissue

• complement helps acute inflammation and phagocytosis, enhances inflammation and kills bacteria

what is the purpose of infiltrate in acute inflammation?

i. neutrophils

• phagocytosis

• destroy debris

ii. macrophages

• phagocytosis and immune function

iii. few lymphocytes

• immune function

what is sequela?

• a sequela is any possible result, complication or conclusion of pathological process

  • possible outcome

what are the sequela of acute inflammation?

1. resolution

2. formation of an abscess (pus filled cavity)

3. repair (healing)

   1. regeneration

   2. organisation

4. chronic inflammation