ETE Flashcards
Neoplasia
new growth
Tumour
Tumour - swelling / inflammation
Benign
– microscopically innocent, localised, non-spread, removable
Malignancy
Malignancy – invade adjacent structures, metastasize to distal organs, cure = found early
Anaplasia
Anaplasia - lack of differentiation
What is the cause of neoplasia and tumours?
- Non-lethal genetic mutation leading to tumour cells and excessive and unregulated proliferation
Benign and malignant neoplasm characteristics?
Benign and malignant neoplasm characteristics?
- Clonal neoplastic cells = parenchyma
- Reactive stroma which growth/evolution is dependant on
- Naming based on parenchymal cells affected
How do you name benign neoplasms?
- “-oma” to cell of origin
- Fibrous tissue = fibroma
- Cartilage = chondroma
In Benign neoplasms what are adenomas?
In Benign neoplasms what are adenomas?
- Epithelial benign tumour
How do you name malignant neoplasms?
How do you name malignant neoplasms?
- If of mesenchymal – add “sarcoma”
o Fibrosarcoma
- If of epithelial origin (any 3 germ layers) – add “carcinoma”
o Epidermis (ectodermal origin)
o Renal tubular cells (mesodermal origin)
o Cells lining intestine (endodermal)
If neoplasm is epithelial original & from stratified squamous epithelium or glandular pattern what’s it called?
If neoplasm is epithelial original & from stratified squamous epithelium or glandular pattern what’s it called?
- Squamous cell carcinoma
- Adenocarcinoma
If a neoplasm of epithelial origin is tissue origin as well…?
- Bronchogenic squamous cell carcinoma
- Renal cell carcinoma
What’s the difference between carcinoma vs. Sarcoma?
- Carcinoma = skin or tissue cells lining internal organs (kidney, liver)
- Sarcoma = grows in body’s connective tissue (fat, blood vessels, nerves, bones, cartilage)
Name 3 characteristics of benign and malignant tumours & germ layers?
Name 3 characteristics of benign and malignant tumours & germ layers?
- contain cells from single germ layer
- more than one germ layer = endo, meso, ectoderm = teratoma
o well differentiated = benign teratoma
o poorly differentiated = malignant teratoma
Benign & Malignant Neoplasms – Differentiation / Anaplasia
Benign & Malignant Neoplasms – Differentiation / Anaplasia
Benign
- WELL differentiated
- E.g. lipoma – parenchymal cells almost identical to adipocytes
Malignant tumours
- Differentiated or completely Undifferentiated parenchymal cells
- E.g. thyroid adenocarcinoma = normal appearing follicles
- Squamous cell carcinoma = normal squamous epithelial cells
Differentiation/ anaplasia of malignant neoplasms? What does anaplasia do?
Differentiation/ anaplasia of malignant neoplasms? What does anaplasia do?
- POORLY differentiated = ANAPLASTIC
- Anaplasia =
o Pleomorphism – varied size, shape
o Abnormal nuclear morphology – abundant chromatin
o Mitoses – cell division (M phase) - proliferative
What does differentiation and anaplasia cause to the body?
What does differentiation and anaplasia cause to the body?
Loss of polarity
- Cells grow together
Abnormal nuclear morphology
- Tumour giant cells
Metaplasia
- Replacement of one cell type with another (e.g. oesophageal reflux)
Do well differentiated tumours retain cellular function? And how do we detect glandular hyperplasia?
Do well differentiated tumours retain cellular function? And how do we detect glandular hyperplasia?
- YES – poorly differentiated don’t
- E.g. glandular adenomas = increased hormone production
- Cellular products can be measured in blood to detect glandular hyperplasia
o Squamous cell carcinomas elaborate keratin
o Hepatocellular carcinomas secrete bile contents
How long until you can clinically detect a tumour?
How long until you can clinically detect a tumour?
- Palpation or x-ray
- 1 gm = 1,000,000,000 cells
- Cell replications = 1, 2, 4, 8, 16, 32, 64, 128, 256
- Assume cell cycle of 3 days = 30 divisions x 3 days each = 90 days
- 10 more divisions = 1 kg
o MAX compatible with LIFE
o 10 divisions x 3 days = 30 days
o Life expectancy 4 months from first mutation
If a tumour has been detected at >1gm what does this mean?
- Its completed ¾ of its lifespan
- Often too late – mutations allowing it to metastasis
When should we aim to detect cancer cells?
When should we aim to detect cancer cells?
- Earlier stages at <10mg = 24-25 divisions
What 3 factors determine tumour growth?
- Doubling time
- Fraction of cells dividing
- Rate of cell death
Define ‘Rates of growth’ + growth fraction (high & low) + senescent?
Define ‘Rates of growth’ + growth fraction (high & low) + senescent?
- Tumour cell doubling time is equal or greater than normal cells
- More benign (differentiated) neoplasms = lower growth rate and fraction
- Growth faction
o Proportion of cells undergoing division in tumour / number of cells in tumour
o No. of parenchymal cells dividing¬¬¬__ x 100
o No. of cells parenchymal in tumour
o HIGH GROWTH FRACTION = leukemia/ lymphoma, lung cancers
o LOW GROWTH FRACTION = colon, breast cancers (10%) - Senescent
o Cells that stop dividing, die and exit cell cycle
Define tumour kinetics
Define tumour kinetics
- Fast growing tumours = increased cell turnover = increased growth and apoptosis
Why are malignant tumours an exception to growth rate?
Why are malignant tumours an exception to growth rate?
- As they progressively slow their growth with maturation
- Affected by hormones/blood supply
- Tumours that spontaneously resolve are extremely rare = untreated = fatal
How does local invasion affect cancer growth?
How does local invasion affect cancer growth?
Progressive
- Infiltration within parent organ
- Destruction surrounding tissue
- Poor demarcation
- Rows of cell penetrating margin
- No boundaries = breaks skin
- Resection = lots of healthy tissue removed
- Invasiveness defines benign/malignant tumours
What is metastasis?
What is metastasis?
Tumours removed from primary tumour – to secondary organ
Metastatic = malignant
- Cells permeated into vessels, lymphatics, body cavities
- Two malignant cancers rarely metastasise
- 30% patients solid tumours possess mets = poor prognosis
What are the 3 pathways of spread?
1.
What are the 3 pathways of spread?
1. Direct seeding of body cavities/surfaces
2. Lymphatic spread
3. Haematogenous spread
Describe direct seeding of body cavities/surfaces?
- When malignant neoplasm breaks into open field
- Within peritoneal cavity
- Ovarian cancer – all peritoneal surfaces covered
- Metastasis to liver, vertebrae, colon
Describe lymphatic pathways of spread?
Describe lymphatic pathways of spread?
- Most common spreading – carcinomas
- Invade lymphatic vessels, to nodes to follow lymphatic drainage – blood
- E.g. breast cancer – along internal mammary arteries – infra/supraclavicular nodes
- lymph nodes can stop further spread
- symptoms: tumour lump, gland swelling
Describe haematogenous pathway of spread?
Describe haematogenous pathway of spread?
- Sarcomas
- Tumour cells come to rest in first capillary bed
- Tumour cells in renal vein move to the lungs -> in the rental artery move to kidney -> in the small intestine move to liver
- Some vascular sites infrequently involved - muscle, spleen due to a phenomenon termed homing
Summary for distinguishing benign/malignant neoplasms
Benign - e.g. leiomyoma
- slow growing
- non-inavasive
- well differientiated
Malignant (leiomyosarcoma)
- large
- rapid growth
- necrosis
- metastatic
- poorly differentiated
Where are neoplasms most common in men and women
Where are neoplasms most common in men and women
Men: prostate, lung, colorectal
Women: breast, lung, colo-rectal
What are the percentages of death rates in cancer?
What are the percentages of death rates in cancer?
- Last 15-20 yrs decreased 18.4% in male top cancers
- Last 10-15 yrs decreased 10.4% in women top cancers
What percentage is environmental and genetic factors influencing sporadic cancer?
- 65% environmental
- 26-42% genetic
How many deaths % does obesity and smoking cause?
How many deaths % does obesity and smoking cause?
Obesity 14-20%
Smoking – 90% lung
What age are most cancer in and why ?
What age are most cancer in and why ?
More than > 55 years
Due to somatic DNA mutation
Decline in immune function
How do cancers genetically develop?
How do cancers genetically develop?
- Autosomal dominant inherited cancer syndromes
- Defective DNA repair syndromes
- Familial cancers
How do non-hereditary factors cause cancer?
- Develop at sites of chronic inflammation
- Asbestosis, GI inflammation, H. pylori (causes compensatory proliferation, production of ROS)
- Precancerous conditions
o Chronic gastritis, UC
What are key features/pre-recs of cancer development?
What are key features/pre-recs of cancer development?
- Non-lethal damage
o DNA mutation via environment or inherited
- Tumours formed by expansion of single damaged cell
What four classes of mutations predisposed to cancer?
What four classes of mutations predisposed to cancer?
1. Growth promoting oncogenes
2. Growth inhibiting tumour suppressor genes
3. Genes regulating apoptosis
4. Genes involved in DNA repair
What mechanisms of cancer development are there?
What mechanisms of cancer development are there?
Carcinogenesis multistep process
- Tumour cells possess multiple genetic mutations
- Excessive growth, metastasis
- Cells become more malignant
Transformation
Progression
Proliferation of genetically unstable cells
Tumor cell variants heterogeneity
What are the 7 key attributes in tumour malignant transformation?
What are the 7 key attributes in tumour malignant transformation?
1. Self-sufficiency in growth signals – oncogene activation
2. Insensitivity to growth inhibition – TGFb, CDKs
3. Evasion of apoptosis – p53 inactivation
4. Limitless replicative potential
5. Sustained angiogenesis
6. Ability to invade/metastasise
7. Defects in DNA repair
What are oncogenes?
What are oncogenes?
Genes controlling autonomous growth
Created by mutations in proto-oncogenes
Describe what RAS oncogenes are?
Describe what RAS oncogenes are?
- G protein that binds to guanosine phosphate (GTP)
- Activation of GFRs dissociates GDP from RAS
- When GTP binds to RAS, activation downstream MAPK pathway, floods nucleus with mitogenic stimuli
What are the most important cyclins?
What are the most important cyclins?
D, E, A, B
Cyclins bind to CDKs, phosphorylate proteins and drive cell cycle
Cyclin D binds CDK4 drives G1
Describe cyclins, CDKs and inhibitors role in the cell cycle:
Describe cyclins, CDKs and inhibitors role in the cell cycle:
D-CDK4/6, E-CDK2 regulate the G1-S transition by phosphorylation of the RB protein. A-CDK2/1 are active in the S phase. B-CDK1 is essential for the G2-M transition. Two families of CDKIs can block activity of CDKs and progression through cycle – p16, 15, 18, 19 act on C-CDK4/6. P21, 27, 57 can inhibit ALL CDKs.
What are the 3 insensitivities to growth inhibition?
What are the 3 insensitivities to growth inhibition?
1. Quiescence - Activation temporary cell cycle arrest
2. Senescence – induction permanent cell cycle arrest
3. Apoptosis – triggering cell cycle arrest
How does the invasion of apoptosis occur?
How does the invasion of apoptosis occur?
- Mutations in genes promote apoptosis = increased cell growth = neoplasia
- Apoptosis = programmed cell death to prevent damaged cell reproducing
- Extrinsic apoptosis
o Fas receptors
Invasion of cell apoptosis summary:
Invasion of cell apoptosis summary:
Cancer cells evade apoptosis
- Mutation = ↓ Fas
- Gain of function = increased BCL-2 protein
o 85% B cell lymphomas
o Increased BCL-2/BCL-XL. ↓ apoptosis
- ↓p53 activity, ↓BAX, BAK
How do cells grow more than >2mm?
How do cells grow more than >2mm?
ANGIOGENSIS – vascularisation
Increased angiogenesis = increased vasculogenesis
Appearance/ morphology freckle
Appearance/ morphology freckle
Appearance
* 1-3mm (small)
* Tan-red
* Light brown macules
o Seen AFTER SUN exposure
Morphology
* Increased pigmentation of basal keratinocytes
* Slightly enlarged (increased synthesis melanin)
Appearance/ morphology Lentigo
Appearance/ morphology Lentigo
* Common
* Benign localised hyperplasia of melanocytes
* Mucous membrane + skin
* 5-10mm
* Tan brown
* DO NOT darken from UV
* Linear melanocyte hyperplasia above basement membrane
Appearance/ morphology Melanocyte Nevus (mole)
Appearance/ morphology Melanocyte Nevus (mole)
* < 6mm (small)
* Flat to elevated, round boarders
* Many types
* Acquired nevi common
* Junction + compound
* Pregnancy (more common as hormonal response)
Morphology
* Junctional
* Aggregates/nest of cells along epi/der boarder
* Nuclei rounded
* Compound
* Nests into dermis
* Epidermal nest can dissipate
* More raised than junctional
* Junctional -> compound = maturation
* Deepening of roots, loss of pigment, low tyrosinase, high cholinesterase activity
* Deep maturation - deep neural like cells - melanoma (no maturation) from benign
* Possible transformation of nevi -> melanoma
What is the skin composed of?
What is the skin composed of?
- Squamous epithelial cells
o Protective keratin protein and cytokines
- Melanocytes
o Epidermis melanin, protection UV
- Dendritic cells
o Epidermis Langerhans cells immune function, migrate to lymph nodes
o Dermis Dendrocytes
What three steps are in the cutaneous immune system?
A.
What three steps are in the cutaneous immune system?
A. Non activated
B. Innate
C. Adaptive
Define the 3 steps, non activated, innate and adaptive of the cutaneous immune system:
Define the 3 steps, non activated, innate and adaptive of the cutaneous immune system:
A. Non activated
a. Absence of inflammation stationary + transitory immune cells survey ready for response
b. Langerhans cells, dermal dendritic cells, granulocytes and monocytes
B. Innate
a. Response to epithelial injury/ antigen presentation = recruits nonspecific effector cells neutrophils and eosinophils
b. Inflammation, activated Langerhans cell, cytokines and chemokines attacked by activated dendric cell + fibroblast and migrate to local lymph node
C. Adaptive
a. When antigen presented recognised by T cells antigen-specific skin-homing T cells recruited, T cell receptor response
b. Activated langerhans cell, dermal fibroblasts, dendric cells with TCR + CLA T cells recruited to right antigen
5 Steps of maturation of non-dysplastic nevi
5 Steps of maturation of non-dysplastic nevi
* A - Normal skin - scattered dendritic melanocytes within epi basal cell layer
* B - Junctional nevus
* C - Compound nevus
* D - Dermal nevus
* E - dermal nevus with neurotization (extreme maturation)
Describe Dysplastic nevi: precursors, morphology, pathogenesis (5 steps)
Describe Dysplastic nevi: precursors, morphology, pathogenesis (5 steps)
Precursors:
- Precursor to melanoma
- Flat, raised, dark pebbly surface
Morphology
- Enlarged and can fuse together
- Nevus cells replace basal membrane
- Enlarged irregular nucleus
- Release of melanin dermis
Pathogenesis
* Development nevi -> melanoma stepwise process
o Mutations, epigenetic changes
CDKN2A, CDK4 (Dysplastic nevus syndrome) + NRAS + BRAF
A. Lentiginous melanocytic hyperplasia
B. Lentiginous junctional nevus
C. Lentiginous compound nevus with abnormal architecture and cytologic features (dysplastic nevus)
D. Early melanoma/ in radial growth phase
E. Advanced melanoma (vertical growth phase) with malignant spread into the dermis and vessels
Define aetiology, pathophysiology, morphology + clinical presentation of MELANOMA
Define aetiology, pathophysiology, morphology + clinical presentation of MELANOMA
Clinical features
- Asymptomatic
o Itching pain
o Changes in colour/shape
o ABCDE - Asymmetry, irregular Boarder, uneven Colour, Diameter, Evolving
Morphology
- Radial growth – NO metastasis
- Shift to vertical growth
o Deep dermal infiltration
o Needs excision – melanocytes
Pathogenesis
- Inherited factors + sun exposure
o Upper back for men and legs for women
o 10-15% family
o Mutations in RB tumour suppressor protein
Define aetiology, pathophysiology, morphology + clinical presentation of SQUAMOUS CELL CARCINOMA (SSC)
keratosis of basal cells in epithelium, ↑ stratum corneum
* Second most common tumour -sun
* More men than women
* Detected small and excised
* Epidermal SSC are – scaly red lesions, advanced lesions may ulcerate
MICRO Morphology
* Atyptical enlarged hyperchromatic nuclei
* All levels of dermis: areas of keratinisation, necrosis and stratum corneum
INVASIVE morphology
* Lesions nodular and ulcerated
* “tongues” of atypical squamous epithelial have gone into basement membrane into dermis
Pathogenesis
* DNA damage UV radiation – sun
* Immunosuppression
* Tobacco
* P53 mutation in acitic keratosis
Define aetiology, pathophysiology, morphology + clinical presentation of BASAL CELL CARCINOMA
dilated blood vessels, basal cell proliferation, usually in epithelium
* Most common invasive cancer
* Slow growing, rarely metastisise
* On sun exposed skin
Morphology
* Pearly papules (purple like blobs)
* Invades bone, facial sinuses
* Tumour cells resemble normal basal cells
o Multifocal growths
o Nodular lesions
Stroma retracts away from carcinoma
Pathogenesis
* One allele mutated, second allele acquired by UV exposure
* 40-60% have p53 mutations
o 60% of these UV radiation hallmark
What’s the basic structure of blood vessels?
What’s the basic structure of blood vessels?
- Endothelial, smooth muscle cells, ECM (elastin, collagen, glycosaminoglycans)
What are the 3 concentric layers in blood vessels?
What are the 3 concentric layers in blood vessels?
- Intima endothelial cells and connective tissue
- Media internal elastic lamina, smooth muscle cells, external elastic lamina)
- Adventitia connective tissue, nerve fibres, vasa vasorum
What is the structure and function of arterial categories?
- Large + elastic
- 2mm – 100 um
- Configuration based on metabolic needs
- Changes in ECM and media – aging
What are the three main processes of vessel development, growth and remodelling
What are the three main processes of vessel development, growth and remodelling
1. Vasculogenesis
a. Formation of blood vessels in utero VEGF growth factors essential quiescence induced by pericytes
2. Angiogenesis
a. Formation of new vessels in adulthood
3. Arteriogenesis
a. Remodelling/ adaptation of arteries
What is the response of vascular components due to injury?
What is the response of vascular components due to injury?
- Endothelial cells
o Maintain non-adherent neutral surface prevents haemostasis
o Possess different transcriptional activities along vascular tree
Endothelial cells and pericytes remain impermeable
o Can become activated induce gene expression
Cytokines, lipids, viruses
Normal when rectified - Endothelial dysfunction
o Altered phenotype
o Impaired vasoreactivity
o Adhesive to inflammatory cells increased thrombosis, atherosclerosis - Vascular smooth muscle cells
o Vascular repair
o Proliferate, synthesise ECM collagen, elastin + cytokines
o Respond to physiological stimuli regulate vascular tone PDGF, endothelin-1, INF-y, IL-1
What does intimal thickening cause?
- Loss/dysfunction endothelium = VSMC growth = ECM = thickening
- Damage = hyperplasia of VSMC and recruitment of adjacent ECs
o To cover wound
o Thickening is normal
o Neointimal VSMCs can divide
o Healing permanently increases thickness = prolonged damage = arteriosclerosis + occlusion
1. Recruitment of smooth muscle cells/precursor cells to the intima
2. Smooth muscle cell mitosis
3. Elaboration of extracellular matrix
What is hypertensive vascular disease definition and diagnosis?
Where BP must be maintained
Hypertension = >139 S or >89 D mmHG
* Increased atherosclerosis
* 25% hypertensive
Diagnosis
* Often delayed = silent killer
* Atherosclerosis, renal disease, cardiac hypertrophy
* ½ die of IHD
* 1/3 stroke
Define hypertensive vascular disease in terms of increased/↓ BP
↓ BP
= ↓ dilation = increased nitric oxide, prostacyclin
= ↓ cardiac output = ↓ HR, contractility and blood volume
* CO influenced by NA+ and H2O, ↓pH, hypoxaemia
* Total peripheral resistance influenced by tone and compliance
Increased BP
= increased cardiac output, HR, contraction and volume
= Increased constriction = increased angiotensin II, thromboxane
How are the kidneys and hypertension related?
- Renin-angiotensin-aldosterone system !!!!
o Regulates vasoconstriction and Na+ homeostasis
Renin secretes from juxtaglomerular cells
Then renin + angiotensinogen I to II by ACE in lungs
Angiotensin II stimulates vasoconstriction and aldosterone release = increased Na+ reabsorption = Increased blood volume and pressure
Kidney releases prostaglandins and NO
Myocardium releases natriuretic factors = ↓ Na+ reabsorption
How are tubular cells involved in kidney filtration and hypertensive vascular disease?
- Tubular cells must reabsorb 99.5% sodium from kidneys
o 98% via ion channels
o 2% by renin-angiotensin system
o ↓ Na+ excretion implicated as a final common pathway of essential hypertension
o If pressure increases increases GFR increased Na+ excretion = hypertension slowly develops
Define arteriosclerosis + atherosclerosis
Define arteriosclerosis + atherosclerosis
Arteriosclerosis “hardening of the arteries” – wall thickening/elasticity loss – Mockeberg medical sclerosis (calcified sclerosis of muscular arteries)
Atherosclerosis “gruel and hardening” – IHD/stroke
What is the epidemiology of atherosclerosis
What is the epidemiology of atherosclerosis
* High in western countries
* Age, gender, genetics
* Premenopausal women lower risk – protected by estrogen
* Post menopausal women higher risk
* Modifiable risk factors – hyperlipidemia, hypertension, smoking, diabetes
* Other risk factors – inflammation, metabolic syndrome, lazy
In atherosclerosis what 2 modifiable risk factors play a big role?
- Hyperlipidemia and hypercholesterolemia
o Stimulate atherosclerosis development LDL
o LDL delivers cholesterol to tissues
o HDL transprots lipids from tissue to liver
o Diet big role
Omega 3 = ↓ LDL
Exercise + alcohol = increased HDL
Obesity + smoking = ↓ HDL
What biochemistry levels should you be at in cholesterol?
Total, HDL, LDL
* Normal / high risk tryglycerides = less 1.1 / more 2.1 mM
* Normal / high risk cholesterol = more 6.2 mM total
What 3 causes cause atherosclerosis
Hypertension
* Systolic and diastolic pressure high = increased risk by 60%
Smoking
* One pack per day doubles risk
DM
* Induces endothelial damage
* Diabetic = double risk
What is the pathogenesis of atherosclerosis? 2 ways
2 main
1. Intimal hyperplasia
2. Vascular thrombus formation
a. Response to injury
b. Response to retention
c. Oxidative modification hypothesis
Drawing of pathogenesis of atherosclerosis
- Chronic endothelial injury
a. Hypertension
b. Smoking
c. Toxin
d. Virus - Response to injury – endothelial dysfunction
a. Increased permeability, monocyte adhesion + emigration - Smooth muscle recruitment to intima
a. Macrophage activation - Macrophages and smooth muscle cell engulf lipid
- Smooth muscle proliferation, collagen, and other ECM deposition, extracellular lipid
What is the cell progression of atherosclerosis
Preclinical phase
= Normal artery fatty streak fibrofatty plaque advanced vulnerable plaque
Clinical phase
= wall weakening – aneurysm + rupture plaque rupture – occlusion by thrombosis progressive plaque overgrowth – critical stenosis
What consequences are there from atherosclerosis?
- Stenosis = Blockage to blood flow, initial complication, exertional angina (70% occlusion)
o Can cause cardiac/gut/muscle/brain ischaemia pain/necrosis - Plaque eruption/ thrombosis = partial / complete flow restriction, acute ischaemia
What is an aneurysm ?
What is an aneurysm ?
* Localised abnormal dilation of blood
What is a dissection?
What is a dissection?
* Blood enters arterial wall, dissects vascular intima and adventitia and leads into the media
Pathogenesis of vascular aneurysm
Pathogenesis of vascular aneurysm
* Vascular damage overwhelms ECM connective tissue
Name 2 diseases/ conditions of aneurysm and dissection?
Name 2 diseases/ conditions of aneurysm and dissection?
* Marfan syndrome
o Poor quality ECM
o Defective fibrillin
o Poor TGF-B activity
* Vitamin C deficiency
What is abdominal aortic aneurysm (AAA)
*
What is abdominal aortic aneurysm (AAA)
* Caused by Atherosclerosis, hypoxia, necrosis,
o Thrombosis
o Males >50 yr old
Morphology
* 25 cm long, 15cm wide
* Intima shows atherosclerosis
Clinical consequences
* Peritoneal haemorrhage
* Occlusion distal artery
* Lower limb embolism
* Abdominal mass
* Morality rate pre-rupture surgery 5%. POST = 50%
Give aneurysm treatments
Give aneurysm treatments
- Surgical clipping = prevents blood into aneurysm and rupture
- Endovascular coiling/stent = impedes blood flow into aneurysm and rupture
Describe aortic dissection
Describe aortic dissection
When blood separates intima/media/adventitial layers
* Common in 40-60 yrs old men
Describe pathogenesis of aortic dissection
Describe pathogenesis of aortic dissection
* Hypetension – ischemic injury
* Marfan syndrome – affects ECM deposition and weakens arterial wall
How much blood does the blood pump?
How much blood does the blood pump?
* 6,000 L/day
* 40 million x a year
* Most common death world wide 1/3 deaths less than 75 yr old
Describe structure / function of heart?
Describe structure / function of heart?
* 250-350g
* Wall = RV 0.3-0.5cm & LV = 1.3 cm-1.5cm
* SA node fasted beat 60-100 bpm
* Conduction system – muscle – electrically excitable – Ca2+ release – actin/myosin – SA node – AV node – bundle of his – right/left bundle branches – purkinje network
Name 3 main causes of heart valve dysfunction?
Name 3 main causes of heart valve dysfunction?
1. Nodular calcification
2. Direct collagen damage
3. Fibrotic thickening
What 6 factors cause cardiac dysfunction?
What 6 factors cause cardiac dysfunction?
1. Pump failure
2. Blood flow obstruction
3. Regurgitant flow
4. Shunted flow
5. Cardiac conduction
6. Rupture of heart vessel
IHD # of death/year and causes ?
IHD # of death/year and causes ?
7 million!!!!
* Caused by myocardial ischemia
o Lack of oxygen and nutrients
o 90% IHD = atherosclerotic blockage
* IHD is a late manifestation of CAD
What is IHD empidemiology
*
What is IHD empidemiology
* 500 K American die/year
* 50% less than 20-30 yrs ago
* ↓ smoking, medication, surgery helps
* Mortality rates increasing atm = fatty foods
What is IHD empidemiology
*
What is IHD empidemiology
* 500 K American die/year
* 50% less than 20-30 yrs ago
* ↓ smoking, medication, surgery helps
* Mortality rates increasing atm = fatty foods
IHD pathogenesis
IHD pathogenesis
1. Normal
a. Atherosclerosis
2. Fixed coronary obstruction
a. Plaque disruption OR
b. Severe fixed coronary obstruction = IHD
3. Thrombosis causes
a. Mural thrombosis with obstruction
b. Occlusive thrombosis
Difference between stable angina and unstable angina
Difference between stable angina and unstable angina
Stable angina → where arteries are stenosed
Unstable angina → plaque rupture + partial thrombosis + vasospasm
List times of myocardial responses
List times of myocardial responses
Onset of ATP depletion = seconds
Loss of contractibility = less 2 mins
ATP reduced to 50% = 10 min
ATP reduced to 10% = 40 min
Irreversible injury = 20 min-40 min
Microvascular injury = more 1 hr
Consequences of MI
Consequences of MI
Heart rupture
1. Of necrotic/inflamed free wall (3-7 days)
2. Ventricular septum (L/R shunt)
3. Papillary muscle (regurgitation)
Pericarditis Myocardial inflammation extends into pericardium (2-3 days)
Right ventricular infarction Results in venous congestion, systemic hypotension
