Basic Pathology Notes for Final

Section B 

1. Introduction

Define pathology

• Patho=suffering/disease; logy=study of 
• scientific study of disease
• structure, functional changes in cells, tissues and organs underlie disease

Define disease

• abnormal variation in structure or function of any part of body
• pattern of body response to some form of injury that causes a deviation form or variation of normal conditions 

Importance of pathology

• screening 
• diagnosis
• manage condition
• monitoring complications 
• treatment
• prevention 
• generate prognosis 

Etiology

• primary
• idiopathic

Acquired factor

• physical agents
• chemical agents 
• nutritional imbalance
• infectious agents
• immunological reactions
• psychogenic factors 
• oxygen deprivation (hypoxia, ischemia)

Genetic factor

• development defects (morphogenesis)
• cytogenic defects (chromosomal)-Turner, Down syndrome
• single gene defects (Mandelian syndrome)
• Thalessemia (reduce hemoglobin)
• Sickle cell anemia 
• storage disease
• disorders with multifactorial inheritation 
• Achondroplasia
• Autosomal dominant disease
• Retinoblastoma

Signs & symtoms

• signs objective
• signs visible, can be verified
• signs indicative conditions doctor see, symptoms sensed by patient 
• signs: blood pressure, temperature, pulse rate
• symptoms: nausea, stomachache, fatigue 

2. Inflammation

Define

• Latin-inflammare-to burn
• response to injury

Common cause

• microbial infections
• hypersensitivity reactions
• tissue necrosis
• physical agents, irritant & corrosive chemicals

Chemical mediators

• phagocytes
• host cells, leukocytes, endothelium, mast cell
• plasma protein
• infection-resident cells sense-secrete inflammatory mediators

Inflammatory mediators

• produced from plasma protein
• promote efflux of plasma
• recruitment of leukocytes 
• activation of leukocytes-phagocytosis
• damage to normal cells

Cardinal signs

• Rubor: redness due to vasodilation 
• Calor: heat results from hyperemia
• Tumor: swelling/edema-accumulation of fluid in EV space-increased vascular permeability
• Dolor: pain-stretching & destruction of tissues-chemical mediators of inflammation
• Functio laesa: loss of function=swelling+pain

Acute & Chronic 

• acute short duration
• acute neutrophils & macrophages, chronic mononuclear cells
• acute outcomes resolution, abscess formation chronic inflammation, chronic outcomes tissue destruction, fibrosis
•  acute physiologic, chronic pathologic
• acute mild tissue damage, chronic severe

Morphology of acute

• serous
• fibrinous
• suppurative
• catarrhal
• pseudomembranous
• hemmorhagic

Local & systemic effects 

• vascular endothelium-increased leukocytes adhesion, migrate to site of injury
• leukocytes-activation
• fibroblasts-proliferation

• capillary dilatation cause rubor and calor
• exudation of fluid, increased permeability
• emigration of leukocytes-increased leukocytes adhesion, migrate to site of injury
• fever
• endocrine & metabolic response
• leukocytosis
• increased heart rate and bp
• rigors
• malaise

Chemotaxis

• movement of motile cells in a direction corresponding to a gradient of increasing/decreasing concentration of particular chemotactic agent

Phagocytosis

• bind, engulf, digest, pseudopodia

Systemic lupus erythematosus SLE

• chronic autoimmune disorder
• immune system attacks body
• confuses itself
• butterfly rash
• mouth ulcers, blood in urine, hair loss, fever, anemia, high bp
• complications: heart attack, stroke, kidney failure, pericarditis, vasculitis

3. Healing and Repair

Define

• replacement of destroyed tissue by living tissue

Regeneration

• generare-bring to life
• renewal of lost tissue-replaced by identical ones

Features 

• inflammation
• angiogenesis
• migration & proliferation of fibroblasts 
• scar formation
• connective tissue remodeling

Close wound 

• soft tissue injury beneath skin-bruise

Open wound

• abrasion, puncture, laceration, avulsion

First intention/primary union 

• short duration
• clean wound
• minimal tissue destruction
• scanty granulation tissue
• no wound contraction

Second intention/secondary union

• longer time
• open wound
• more intense inflammation
• large amount of granulation tissue 
• wound contraction

4. Neoplasm

Benign & Malignant

• benign slow growing
• benign capsulated
• benign non-invasive
• benign do not metastasize
• benign well differentiated, malignant poor
• suffix benign oma, malignant sarcoma & carcinoma

Metastases

• spread of a malignant tumor from one site to another via blood or lymph
• transcoelomic spread
• penetrates into body cavity
• Krukenburg tumor: adenocarcinoma-GIT, pancreas, breast, gall bladder
• Pseudomyxoma peritonii: ovary, appendix, bladder, GIT-cause fibrosis, mucin fill abdominal cavity 
• lymphatic spread
• lymph nodes-senital nodes receives lymph flow from primary tumor-lymphatic vessels-breast & large intestines
• hematogenous spread
  
• emboli formation by aggregation
• adhere to circulating leukocytes particularly platelets
• capillary wall into tissue
• kill by WBC or die
• stick to platelets to form clumps
• lung, liver, brain & bones
• carcinoma of liver, kidney, bone 

5: acute lymphoblastic leukemia/lymphoma, neuro/retinoblastoma, rhabdomyosarcoma, Wilm's tumour (nephroblastoma), yolk sac tumor of the testis

6~15: osteosarcoma, Ewing sarcoma, primitive neuroectodermal tumor PNET, medullablastoma 

common cancer: breast, cervical, lung, colorectal, nasopharyngeal 

male: lung, prostate, colorectal, stomach, liver

female: breast, colorectal, lung, cervical, stomach

autosomal resessive: Xeroderma Pigmentosium, Ataxia Telangietasia  (Louis-Bar), Bloom–Torre–Machacek syndrome, Fanconi Anemia

Carcinoma in situ

• Cancer that has stayed in the place where it began and has not spread to neighboring tissues

3 microscopic features of tumors 

Grading

• Grade I: slow growing, well differentiated cancer cell-less aggressive, less likely to spread quickly
• Grade II: somewhat abnormal, moderately differentiated, growing faster 
• Grade III: fast growing, poorly differentiated, more aggressive, more likely to spread  
• more stroma between glands
• distinctively infiltrative margins
• irregular masses

Section C

1. Cell adaptation & Cell injury

Cell adaptation

3 main group of cells 

• Labile (gut lining & epithelial) rapid proliferation and cell turnover
• Stable (hepatocytes) slow in proliferation and cell turnover
• Permanent not able to proliferate 

Atrophy

• decrease in size of cells
• decreased metabolic activity
• reduction in structural components (mitochondria)
• diminished functions but not dead
• Physio: aging process, thymus atrophy during early childhood 
• Patho: CVA, paralyse due to trauma 

Accident

• muscle atrophy
• decrease in size of cells 
• decreased workload
• loss of cell substances
• loss of innervation
• body breakdown muscle conserve into energy
• patient remains immobilize

Hypertrophy

• increase in size of cells
• increased workload
• increased numbers of IC organelles
• increased protein synthesis 
• in permanent cells
• Physio: muscle increase in body builder, uterus during pregnancy
• Patho: Enlargement of left ventricle (hypertension)

Hyperplasia

• increase in number of cells
• increased transcription factors
• increased growth factors
• increased output of cell from stem cells 
• in stable cells
• Physio: hormonal hyperplasia (breast during pregnancy), compensatory hyperplasia (liver after hepatectomy)
• Patho: endometrial hyperplasia, Benign prostatic hyperplasia (BPH)

Liver transplant

• compensatory hyperplasia
• increase in number of cells 
• increased growth factor 
• promotes cell division
• cell proliferation turned off after restoration

Metaplasia 

• replacement/transformation of one adult (differentiated) cell types to another
• reprogramming in stem cells 
• mediated by signals from cytokines , GF
• induction for specific transcription factors
• Physio: endocervix (columnar glandular-squamous)
• Patho: respiratory epithelium in smokers (columnar-squamous)

Dysplasia 

• abnormality of development 
• morphological transformation
• increased mitotic rate 
• incomplete maturation of resultant cells 

Cervical dysplasia/cervical cancer/neoplasia 

• pap smear

Compare dysplasia & metaplasia

• dysplasia premalignant
• dysplasia irreversible
• dysplasia in epithelium, metaplasia in various types of tissue
• dysplasia disordered cellular development, metaplasia mature

Cell injury 

Reversible & IRreversible 

• R cell can recover to normal stage 
• IR severe cell injury that can lead to cell death

• R blebbing of plasma membrane, IR defects
• R ER swell, IR ER lysis
• R mito swell with small densities (amorphous), IR mito swell with large
• R clumping of nuclear chromatin, IR nuclear changes (karyorrhexis, karyolysis, pyknosis) 
• R autophagy of lysozome, IR rupture
• R aggregation of intramembranous particles, IR myelin figure in cytoplasm
• R aggregated cytskeleton, IR disrupted
• R generalized swelling

3 patterns of cellular changes in reversible injury 

• cellular swelling
• cause some pallor, increased turgor & organ weight
• cloudy swelling, hydrophic vacuolation
• cellular fatty changes
• accumulation of fat in non fatty tissues in parenchymatous organs 
• intracellular accumulation of pigments
• endogenous/exogenous
• melanin-brownish-black-by melanocytes 
• melanoma, nevus, albinism vitiligo
• bilirubin-yellowish-degradation of hemoglobin
• hemosiderin-iron containing in heme-derived from ferritin
• hemorrhage beneath skin
• lipofuscin-yellowish brown-high lipid-atrophic cells/old age
• brown atrophy

Apoptosis

• cellular suicide 
• programmed 
• normal healthy process
• natural caused (pregnant-milk)
• beneficial
• no noticeable symptoms 
• rarely needs tx

• membrane blebbing
• cell shrinkage
• nuclear collapse (nuclear/DNA fragmentation, chromatin condensation)
• apoptopic body formation-engulf by WBC

Necrosis

• premature death of cells in living organism
• unprogrammed
• abnormal
• external factors (infections, trauma, toxins)
• harm
• inflammation
• always require tx

• membrane disruption
• cell swelling and rupture
• metabolic collapse
• ATP depletion
• respiratory poisons, hypoxia
• cell content spill out into cell 

Coagulative necrosis

• infarction-ischemia-all organs except brain-loss of blood supply
• pale, firm, slightly swollen
• retained outline, cytoplasmic & nuclear loss
• Myocardial infarction 
• heart, kidney, spleen, liver

Liquefactive necrosis

• focal bacteria infections-CNS
• creamy yellow (pus)
• lots of neutrophils, cell debris 
• abscess formation
• CVA (stroke), cerebral infarction
• CNS

Fat necrosis

• focal areas of fat destruction
• release of lipase
• formation of calcium soaps
• chalky white
• basophilic
• acute pancreatitis, trauma 
• liver, pancreas

Caseous necrosis

• Caseous-Latin-cheese
• cheese-like
• presence of granuloma
• light yellow to crumbly pasty material 
• TB
• lung

Gangrene necrosis

• superimposed infection 
• bad odor
• reddish-black skin color
• histology, wet or dry
• DM
• legs

2. Endocrine disorders

Pituitary

• Acromegaly
• enlargement of bones-hands, feet, jaws
• etiology: excessive secretion of GH
• sweling of hands, legs, protruding jaw, degenerative arthritis, enlargement of organ
• DI
• etiology: insufficient production of ADH
• excessive thirst, dilute urine, fever, vomit, diarrhea, dehydration
• Hypopituitarism
• hormone deficiency
• Pituitary tumor
• pituitary adenomas: 15% of intracranial neoplasm
• prolactinomas 

Thyroid

• Hypothyroidism 
• Cretinism 
• stunted physical & mental growth
• mental defect, deficient hair & teeth, retarded skeletal growth, reduced BMR
• Myxedema
• thyroxin
• metabolism rate decreased to half
• low BMR & pulse rate, dry skin & coarse hair, face become puffy, depressed sex functions
• Hashimoto
• inflammation
• autoimmune ds
• goitre, fatigue, muscle weakness, weight gain
• Hyperthyroidism
• Grave
• autoimmune ds
• thyroid overactive- excessive thyroid hormones 
• enlarged eyes-muscle swell-pulls eyes forward, weight loss, increase appetite, increase BMR, sweating, nausea, diarrhea
• Goitre
• swelling of larynx/neck 
• not functioning properly
• iodine deficiency
• diffuse goitre, toxic goitre, nontoxic goitre
• Thyroid cancer

Adrenal/supra renal

• Cushing syndrome
• Harvey Cushing 1932
• tumor in pituitary 
• high ACTH-high cortisol
• moon face, hyperglycemia, purple/red striae, stretch arks, weight gain, skin & bone thinning
• Addison
• Dr Thomas Addison
• insufficient steroid hormones
• low bp, muscle weakness, weight loss, fever, diarrhea, headache, sweating
• Primary aldesteronism 
• high mineralocorticoid
• hypernatremia, hypokalemia, high bp & pH of blood, muscle weakness & cramps

Pancreas

• DM
• increased blood glucose
• deficiency in secretion of insulin
• Hypoglycemia
• low than normal blood glucose
• excessive insulin
• hunger, nausea, vomiting, paralysis, blurred vision
• Hyperglycemia
• excessive blood glucose
• not enough insulin, eating too much, less exercise
• dry mouth, headache, increased thirst, frequent urination, blurred vision
• Pancreatitis 
• inflammation
• gallstone, alcohol abuse
• nausea, fever, vomiting, severe abdominal pain, swelling in upper abdomen
• Pancreatic cancer
• adenocarcinoma, adenosquamous carcinomas
• loss appetite, weight loss, painless jaundice, pain in upper abdomen

Ovary 

• Amenorrhea
• absence of menstrual period-reproductive age
• Primary: congenital absence of uterus, Secondary: hormonal disturbance (hypothalamus, pituitary)
• weight gain, hair loss, hot flashes, poor concentration
• Hypogonadism 
• low estrogen
• infertility, hair loss, osteoporosis, breast shrinks, heart disease
• Polycystic ovary PCOS
• unknown cause
• amenorrhea, infertility, hirsutism, high testosterone

Testes

• Hypogonadism 
• Testicular cancer
• abnormal cells in testicle grow uncontrolled
• pain in testicle, dull ache in groin, lump in testicle, lower back pain, feel unusual heaviness in scrotum

3. Cardiovascular system 

Edema

• excess accumulation of fluid-body cavity-interstitial tissue space
• etiology: increased hydrostatic pressure, hypoproteinemia, lymphatic obstruction, sodium retention, inflammation
• types: generalized, localized, renal, lymphatic, skin, pulmonary, peripheral, corneal, cerebral
• functional impairment, pain (increased pressure on local nerves)
• pitting skin, joint aches, skin swelling, fuller hand and neck veins, puffiness of the ankles, face, or eyes

Hemorrhage

• extravasation of blood outside blood vessel 
• etiology: physical trauma, inadequate blood clot
• effects: stroke, hypovolemic shock, anemia
• types: petechiae 1~2mm, purpura >3mm, ecchymosis/bruises >1~2cm,  hematoma

Embolism

• occlusion/blockage of a vessel by embolus transported in bloodstream 
• etiology: thrombus, air bubble, platelet aggregates, fragment of tumour, fat globules, infected foreign material, bits of bone marrow, amniotic fluid
• pulmonary thromboembolism: R of heart to pulmonary trunk & arteries, 95% deep leg veins 
• systemic thromboembolism: arterial circulation, 20% fragment of material from ulcerating atheroma plaque, infarction, 80% arise from L of heart
• cross thromboembolism: patent foramen ova;e, R to L of heart to systemic circulation
•  chest pain, chest tightness, dyspnea, tachycardia

Infarction

• obstruction of blood supply-death of tissue
• etiology: thrombotic/embolic events
• local vasopasm
• expansion of atheroma due to hemorrhage
• external compression of vessels (trauma)
• chest pain, pain in jaws, neck, back, arm, nausea, vomiting, dyspnea

Thrombosis 

• blood clot in vascular system-obstruction-ischemic injury
• etiology: endothelial injury-platelet adhesion, stasis or turbulence of blood flow-laminar flow disruption, blood hypercoagulability-platelets
• swelling in leg, redness/discoloration of skin, pain, unusual warm skin, numbness

Hypovolemic shock

• blood loss-unable to pump
• etiology: trauma-severe injury, hemorrhage, MVA; dehydration-severe vomiting, diarrhea, burns
• anxiety, chest pain, rapid heart rate, blue lips & fingernails, shallow breathing

Cardiogenic shock

• failure of heart as pump
• pump failure-myocardial infarction/conduction disturbances-sudden fall in cardiac output
• obstructive heart failure-pulmonary embolism
• low bp, poor perfusion to vital organs, cool skin, jugular venous distension

Angina pectoris

• chest pain
• risk factor/etiology: age, coronary artery disease, hypertension, obesity, smoking
• choking, chest tightness, dyspnea, sweating, dizziness

MI

• heart attack
• necrosis of heart muscle from ischemia
• etiology: hypertension, diabetes, smoking
• vasopasm, formation of thrombus
• chest pain, dyspnea, rapid & weak pulse, asymptomatic

Hypertension

• increased bp
• damages arterial walls
• etiology: genetic, obesity, high sodium intake, excessive alcohol
• asymptomatic early stage, headache, epistaxis, dizziness

4. UTI 

R to L

• infectious agent: bacteria (E. coli)
• reservoir: human
• portal of exit: rectum & anus
• mode of transmission: wiping back to front after bowel movement, sexual activity, bubble bath, tampons, faeces
• portal of entry: urethra
• susceptible host: females, elderly, babies, ppl with diabetes