pathology (özge hoca)

The morphological changes in the body caused by injury or disease

• Incisional biopsy

• Excisional biopsy

• Shave

• Punch

• Tru-cut needle biopsy (Histopathologic examination)

• Fine needle aspiration (Cytopathologic ex.)

• Endoscopic/colonoscopic biopsy

• Cytological smear

• Tissue/organ resection

Take a bit of patient’s healthy tissue if possible

-> compare lesion to patient’s “normal” state

• Histopathological examination

• solid tumor (not cyst) in breast, liver, kidney, lung, soft tissue

• Cytopathologic examination

• lumps, fluid-filled cyst

• Breast, salivary gland (rarely liver or pancreas)

• thin 23-25 gauge needle & ultrasound guide

• fix with 95% ethyl alcohol & stain with Papanicolaou (Pap-smear)

• secretions/liquids: cervicovaginal, pleural, peritoneal, joint spaces, CSF

• place in 10% formalin solution unless otherwise stated (10x more fixative & 10x bigger container than specimen)

  • capsuled organs special technique bc fixative can’t get inside

• Tissue samples for frozen section should not be placed in any fixative solution

1. Fixation (usually 10% formalin)

2. Dehydration (alcohols)

3. Clearing (xylene etc.)

4. Embedd in paraffin blocks

5. cut 4-5 micron sections with microtome

6. stain (usually H&E)

in frozen sample no fixation etc, frozen sample cut via cryotome

• normally few days or even weeks/months

• if fast result needed (f.e. patient kept under anesthesia) sample gets freezed (diagnosis within 15/20min)

• patient details

• location of specimen

• method used

• macroscopic and microscopic features of submitted specimen

• results of applied additional special techniques

• Conclusions and pathological diagnosis

• Comments

Adaptation can also be reversible (back to original or similar state)

• injury mild/moderate -> can recover

• Cellular swelling

  • ER

  • dispersion of ribosomes

  • Mitochondria-> ATP depletion due to reduced oxidative phosphorylation

  • Plasma & Nuclear membrane (mild!)

• Fatty change

• Macroscopic

  • organ pale

  • incr. weight

  • incr. turgor (edema)

• Microscopic

  • small clear vacuoles within Cytoplasm

• Steatosis

• accumulation of Triglycerides (esp. liver & heart bc role in fat metabolism)

• Macroscopic

  • pale/yellow organ

  • incr weight

  • incr size

• Microscopic

  • lipid vacuoles in cytoplasm

• diagnosis (+ stage) via ultrasound

• severe mitochondrial damage

• fragmentation of nucleus

• severe membrane injury (cell m. & lysosomal m.)

• irreversible -> cell death

1. Oxygen deficiency

2. Physical agents

3. Chemical agents

4. Infectious agents

5. Immune reactions

6. Genetic defects

7. Nutritional imbalances

8. Aging

1. ATP loss

2. Mitochondrial damage

3. Calcium homeostasis deregulations

4. Membrane permeability defects

5. DNA and protein damage

6. oxidative stress

cause: hypoxic, chemical or mitochondrial injury

+ ER stress due to unfolded pr. accumulation

Hypoxia -> ATP reduction -> necrosis (+ oxidative stress)

DNA/pr. damage -> increased outer membrane permeability -> apoptosis

• Brain, heart, skeletal muscle, kidney, endocrine glands, bone marrow

• mitochondria has dual control (mitochondrial & nuclear DNA)

Apoptosis bc apoptotic enzymes activated -> unbalance -> apoptosis

Calcium influx also causes mitochondrial damage (membarne more permeable, no ATP) -> necrosis

• Mitochondria: decr. ATP & Necrosis

• Lysosome: enzymes leak (apoptosis & necrosis)

• Plasma membrane: osmotic/ionic unbalance, swelling, apoptosis

Apoptosis bc damaged DNA activates pro-apoptotic enzymes

neurodegenerative diseases f.e. Alzheimers (beta-amyloid pr.) , Parkinsons, Huntingtons

• Apoptosis

  • physiologic or pathologic

  • self-induced/planned

  • creates apoptotic vacuoles

  • ATP required

  • intact cell membrane -> no inflammation

• Necrosis

  • pathologic

  • creates apoptotic bodies (pink/eosinophilic)

  • no ATP needed

  • disrupted cell membrane -> inflammation

1. During embryogenesis (oocyte reduction)

2. Due to hormone withdrawal (menstruation)

3. Loss in proliferating cell populations (epith. cells in intestinal crypts; immature lymphocytes in bone marrow)

4. Elimination of self-reactive lymphocytes (otherwise autoimmune disease)

5. After the loss of useful purpose (lymphocytes at end of immune response)

1. DNA damage

2. Accumulation of misfolded pr./ER stress

3. Duct obstruction

4. Infections

• balance between apoptotic & anti-apoptotic enzymes

• Anti-apoptotic: BCL2, BCL-XL, MCL1

• Apoptotic: BAX, BAK

1. Karyolysis: Nuclear fading

2. Pyknosis: N. shrinkage

3. Karyorrhexis: N. fragmentation

1. Coagulative necrosis

2. Liquefactive necrosis

3. Gangrenous necrosis

4. Caseous necrosis

5. Fat necrosis

6. Fibrinoid necrosis

• Cause

  • ischemia

  • denaturation of structural pr. & lysosomal enz.

• Appearance

  • Macr. -> firm tissue

  • Micr. -> preserved cell outlines (1-2 days)

• Organ

  • solid organs: heart, liver, kidney, spleen

• Cause

  • ischemia

  • Bacterial infections

  • enzymatic digestion -> abscess

• Appearance

  • Macr. -> Tissue liquidy/creamy yellow puss

  • Micr. -> Neutrophils and cell debris

• Organs: Brain

• Gangrenous coagulative necrosis -> dry gangrene

  • dry, black, shrunken skin (lower leg)

  • arterial occlusion

  • f.e. cold temp., tissue damage, diabetes)

• Gangrenous coagulation. & liquefactive necr. -> wet gangrene

  • moist, soft, shiny, dark, abscess (bowel)

  • venous obstruction

  • bacteria

  • subtype gas gangrene (Clostridium perfringens, muscle injury, urgent & fatal)

• Cause

  • M. tuberculosis, granuloma formation (necrotizing gr.)

• Appearance

  • cheese-like (lor peynir)

  • fragmented cells & granular debris

• Organ

  • lung (sometimes kidneys, lymph nodes, vertebra)

• Cause

  • activated lipases (release fatty acids from triglycerides -> complex with calcium)

• Appearance

  • Macr. -> white chalky deposits

  • Micr. -> Basophilic calcium deposits, inflammatory reaction, necrotic fat cells

Patient history! Breast trauma, acute pancreatitis, pancreas trauma

-> might think of cancer bc fast growth but actually fat necrosis (also fast growth but not malignant)

• Cause

  • Immune reactions involving blood vessels (Ag-Ab-compl. + fibrin)

• Appearance

  • Only micr. -> pink (eosinoph.) fibrin-like deposits in vessel walls (thickened)

• Organ

  • vessels in autoimmune diseases (e.g., systemic lupus erythematosus) or malignant hypertension

• Hypertrophy: incr size, incr function

• Hyperplasia: incr number, incr function

• Atrophy: decr size

• Metaplasia: change in phenotype/appearance

• Dysplasia: change in size, shape, arrangement etc.

Physiological hypertrophy (bc exercise)

hormones & growth factors (bc incr demand)

balanced growth, improved function, reversible if stimuli removed

Pathological hypertrophy (esp. left ventricle)

more pr. & myofilaments bc incr force needed (disorganized growth)

compensation mechanism (might lead to failure)

Physiological hypertrophy in child (asymptomatic)

Pathological hypertrophy if chronic, nasal obstruction, treatment recquired

Together unless cell doesn't have capability to divide (essential for hyperplasia)

• physiologic

  • breast tissue during puberty or pregnancy

  • liver regeneration after transplant (donor & recipient)

• pathologic

  • endometrial hyperplasia

  • ductal/lobular hyperplasia (breast)

  • benign prostatic hyperplasia

  • chronic liver regeneration -> cirrhosis

… hypertrophy and/or hyperplasia

… atrophy

• physiologic

  • regression of embryological str. (f.e. thyroglossal duct…)

  • uterine involution after pregnancy

  • vaginal atrophy after menopause, breastfeeding

• pathologic

  • disuse (after fracture, bed rest…)

  • loss of nerve innervation

  • decreased blood supply

  • inadequate nutrition

  • loss of endocrine stimulation

  • tissue compression

  • vaginal atrophy after ovary removal surgery

precursor cells differentiate along a new pathway due to chronic irritation (physical or chemical)

• smoking cigarettes -> squamous metaplasia

  • normally resp epith ciliary columnar -> becomes squamous to survive (more resistant) but looses cilia

• GastroEsophagealRefluxDisease (GERD) -> columnar m.

  • squamous epith in esophagus -> becomes columnar (like in stomach) to be resistant to stomach acid

• sometimes not considered adaptation because prestage of carcinoma (not cancerous but can lead to cancer easily)

1. Inadequate removal of an endogenous substance due to defect packaging and transport

   • fatty liver (triglycerides)

2. Genetic or acquired defects in folding, packaging, transport or secretion of an endogenous substance

   • accumulation of abnormal proteins

3. Failure to degrade a metabolite (endogenous) due to inherited enzyme deficiencies

   • lysosomal storage disease (cholesterol/cholesterol esters accum.)

4. Deposition and accumulation of an abnormal exogenous substance

   • carbon

• Atherosclerosis (plaque in artery)

• Xanthomas (acc. in subdermal area)

• Cholesterolosis (strawberry-like mucosa; microscope pink; may lead to polyps, stones or mucosal damage)

• Lysosomal storage diseases (e.g Gaucher’s disease, Niemann-Pick disease)

• Endogenous

  • Melanin

    • brown-black; skin & iris; freckles & nevus

    • produced by melanocytes in epidermis (tyrosinase)

    • defense mech. against UV (more dark freckles in summer)

  • Lipofuscin

    • yellow-brown

    • free radical injury & lipid peroxidation or age related

    • liver, heart, kidney, skin (aging), malnutrition, cancer

  • Hemosiderin

    • yellow-brown

    • excess iron -> ferritin forms hemosiderin granules within cells

    • Hemosiderosis (no tissue damage, f.e. bruise) or Hemochromatosis (tissue damage esp. dangerous in liver, heart, endocrine organs)

• Exogenous

  • carbon/coal dust

    • anthracosis (lungs & lymph nodes black)

  • tattoo

    • inoculated pigment phagocytosed by dermal macrophages

    • no inflammation

• Dystrophic

  • calcium salt accumulation due to tissue damage/necrosis

    f.e. aging, damaged heart valves, atherosclerosis

• Metastatic

  • calcium salt accumulation in healthy tissue due to systemic problem (metastatic-> moves)

    f.e. high serum Ca2+, defective Ca2+ metabolism

• incr. PTH

• bone resorption

• Vit. D disorder

• Renal failure