CSB520 FINAL

Explain the normal adaptations that smoking causes in the airways and what pulmonary pathologies are more likely to occur

Smoking irritates the ciliated epithelium of the conductive airways

- hyperplasia of goblet cells increased mucus secretion

- metaplasia of simple ciliated cells to stratified squamous cells

pathology from loss of mucociliary

- COPDS

- respiratory infections and injury

- emphysema (increased inflammatory mediators

- primary lung cancer (increase cell division)

What is the significance of saying that a tumour found in the lung is "undifferentiated"

Undifferentiated

- malignant

- cells no longer resemble the cell type that the cancer arose

- aggressive and resistant to treatment

What is the most common malignancy diagnosed/found in the lungs

metastatic cancer

Why do the lungs frequently become involved in metastatic cancers

venous blood returns to the lungs for re-oxygenation

There are a number of mechanisms that protect the respiratory portions (alveoli) of the lungs, what factors may compromise or overcome these?

Anything that damages the cilia on the epithelium will compromise our defense against particulate inhalation

- smoking

- asthma

- CF

- inflammation

- damage from heat/acute smoke from fire, very cold air

- loss of the cough reflex and prolonged bed rest = wet lungs

lobaropneumonia host and infectious agent

- high virulence, which are either breathed in or travel to the lungs during sepsis.

- affect anyone who encounters it

- results in a strong acute inflammatory response that affects the entire lung or lobe of a lung.

bronchopneumonia host and infectious agent

- common,

- affecting immune-compromised individuals

- opportunistic infection

Outcomes of pneumonia

resolution (healing without scarring)

organization (healing with scarring)

chronic inflammation.

Resolution usually occurs in this case but organization may occur following necrosis

Complications of pneumonia

- Pleurisy/pleuritis = fluid leaks into pleural lining = pain and scarring

- abscess

- fibrosis

- sepsis and infections in other organs

factors determine whether inhalation of the particulate causes disease

- size

- shape

- solubility

- toxicity

- amount

What aetiological agent is common to all 4 COPD's

smoking

What type of reaction occurs in atopic asthma, explain what occurs during the attack

- Type 1 hypersensitivity response associated with allergy.

- TH2 cells cause IgE secretion of B cells following maturation to plasma cells.

During the attack - release of histamine, serotonin and leukotrienes.

- inflammatory mediators cause increased mucous secretion from goblet cells and deeper mucous-producing glands so that the lumen of the airways is full of mucous

- hyperaemia and oedema occurs in the walls of the airways (the walls are now thicker and oedematous).

- contraction of the smooth muscle within the walls of the airways leading to bronchoconstriction.

- the bronchoconstriction narrows the lumen of the airways which are full of mucous, and the walls are thick and oedematous.

What changes occur in the airways of people with severe forms of asthma; what does this predispose them to

- Hyperplasia of goblet cells

- hypertrophy of the smooth muscle in airway

- excess mucous secretion = metaplasia of the ciliated columnar cells - become stratified squamous cells.

predispose

- other COPDs

- chronic bronchitis

- pneumonia

definition of chronic bronchitis

- productive cough that persists for at least three months over the course of two years- - causes similar changes to smoking (loss of cilia, thickening of bronchial walls)

What is emphysema

Progressive irreversible destruction of alveolar walls typically without fibrosis.

alveolar walls contain elastic fibers and capillary beds - when lost = increased pulmonary resistance

pulmonary congestion and cause

Pulmonary congestion: passive accumulation of blood within the vessels of the lung caused by obstruction of blood flow through the lungs or the left side of the heart

Cause

- left-ventricular heart failure .......................................... - mitral and aortic valve disease.

- emboli - congestion of veins or capillary beds.... - tumours + mucous plugs + scarring = constriction of the vessel

- Hyperaemia - infection/ necrosis = oedema

What pathology is more likely in an individual suffering from pulmonary congestion

- right side heart hypertrophy = failure

- congestion in vena cava and liver

lethal pulmonary emboli derive from

deep veins in lower limbs

factors predispose to pulmonary embolism

- stasis

- hypercoagulability

Will pulmonary emboli always lead to infarction

Pulmonary emboli do not always cause infarction

- size of the emboli (smaller clots that cause partial vascular obstruction = increase pulmonary resistance and heart workload)

- age

- health (cardiovascular disease)

- young people = good vasculature to maintain tissue and

- old people = infarction - failure and ischaemic heart

innate defences in the conductive & respiratory portions of the lungs

conductive

sneezing, coughing, mucociliary clearance

respiratory

macrophage

Bronchial asthma

Causes - asthma

Extrinsic (allergic) and intrinsic (non-allergic)

Episodic wheezing, cough and dyspnoea

Hyper-reactive ariways - bronchospasms due to smooth muscle contraction

Excessive mucus secretion

Bronchiectasis

Causes - smoking, obstruction, infection

Irreversible and progressive dilation of bronchi and bronchioles

Destruction of elastic and muscle

What is pneumoconiosis, which particles are commonly implicated in Australia & what can they cause

inhalation of particular matter = fibrosis and scarring = loss of function

particles: coal, silica, asbestos

cause

- respiratory failure

- RVF

- primary lung cancer

lungs affected by LVF

- hydrostatic pressure -= pulmonary oedema - increases in lung weight

- pulmonary congestion

how do lungs contribute to RVF

- Left side failing first

- Scarring or obstruction in lungs

- Pulmonary emboli - resistance to blood flow in pulmonary circuit

= Lead to pulmonary hypertension

What has happened to the normal renal parenchyma in response to the formation and growth of the cysts

As the cysts form and expand they cause tissue atrophy, the parenchymal cells of the kidney die by apoptosis leaving just the cysts

List the main malignancies that affect the male & female urinary system

- nephroblastoma

- transitional cell carcinoma

- UTI

- renal cell carcinoma

- prostate - adenocarcinoma

List causes of glomerulonephritis & possible consequences

glomerulonephritis - blood born - immune mediated - bilateral

Causes:

- blood borne pathogens

- toxins

- viral infections

- diabetes

Consequences:

- increase in RAAS

- intense rapid hypertension

- proteinuria

- haematuria

major differences between ascending & descending infections

Ascending - going up - only cause damage to one kidney

Descending - going down - by the blood - damage to functional units in both kidneys

Papillary

transitional cell carcinoma

Why are the names of

- nephroblastoma

- Primary renal cell carcinomas

- Papillary carcinoma of the ureter

- Papillary Bladder carcinoma

different

- cell of origin differs

nephroblastoma - unknown

Primary renal cell carcinomas - renal cell

- Papillary carcinoma of the ureter + Papillary Bladder carcinoma

different - transitional cell carcinomas

Why are cancers of the kidney, ureter and bladder generally diagnosed late, what signs and symptoms do patients present with

present with

- blood in urine

- pain

- abdominal mass or obstruction

early stages are asymptomatic

- cancers are usually late and already metastised

descending + ascending - urinary infections differences

descending

- likely affect both kidneys = renal failure

ascending

- infect 1 kidney

- only segment of kidney

Why is pyelonephritis more common in females than males?

1. Shorter urethra

2. Urethral opening closer to the anus

3. Absence of antibacterial properties that are found in prostatic fluid

4. Hormonal changes affecting adherence of bacteria to the mucosa, which assists the spread of bacteria along the urinary tract epithelial linings

5. Urethral trauma during sexual intercourse

what is the papilla

apex of the renal pyramid that projects into the minor calyx

why does papilla become necrotic

analgesic nephropathy - chronic renal disease caused by excessive intake of analgesic mixtures

acute pyelonephritis - diabetics, urinary tract obstruction, ascending infections

Why does glomerulonephritis affect both kidneys

caused by blood born stimuli

Why does glomerulonephritis lead to chronic renal failure

- progression of disease from its origin in the glomeruli to the tubulo-interstitial area and to the blood vessels.

- The arterial vessels in the glomerulus also provide blood supply to other areas of the kidney.

- all areas of the kidney can become involved leading to reduction in function.

common systemic manifestations of renal failure

1. excessive activation of RAAS = angiotensin causes vasoconstriction causing vascular resistance = aldosterone leads to retention of sodium and water causing increase blood volume = systemic hypertension

2. Systemic hypertension = atherosclerosis = left ventricular hypertrophy, ischaemic heart disease, heart failure and cerebral vascular disease

3. Increased blood volume increases hydrostatic pressure leading to transudate oedema - proteinuria as the loss of plasma proteins will reduce plasma colloidal pressure

4. decreased vitamin D activation leads to decreased calcium absorption from gut. Parathyroid hormone is released in response to low blood calcium levels but the kidneys no longer respond to it. Instead, the bones must respond and osteocytes have to break down bone for calcium

5.. Reduced EPO leads to reduced erythropoiesis leading to anaemia leading to lethargy & increased heart rate. Anaemia will be worse if the individual has haematuria

6.. acidosis = no longer secrete bicarbonate ions = decrease in acidity and increase in H+ concentration = hyperkalaemia leading to cardiac arrhythmias.

7. .Increased nitrogenous wastes contributes to chronic poisoning

relationship between systemic hypertension and renal damage

Benign HT leads to renal arteriolosclerosis

- narrows the arterioles renal ischaemia and ischaemic atrophy.

- Renal ischaemia - high blood pressure leads to RAAS

- RAAS - stimulates aldosterone secretion causes sodium and water retention - increased blood volume

- increased vascular resistance, which with increased blood volume leads to increased blood pressure.

Malignant HT

- initiate HT by RAAS

- Cushing's syndrome .

consequence of urinary stone formation

1. pain

2. haematuria

3. obstruction of urine flow

4. predispose to infection

5. more stones

6. chronic irritation

causes of urinary stone formation

- stasis of urine caused by obstruction of urine flow

- infection

- previous stones

- dehydration

- calcium metabolism disorders

what causes hydronephrosis

unilateral - stones, tumour, scarring, subsequent contraction of ureter

bilateral - obstruction, big prostate, cancer, scarring of urethra, foreign object

melanoma

- fewer mutations

- not associated with age

- increased risk with sever sunburn at young age

- genetically predisposed

- grow vertically

- often metastasised at time of diagnosis

skin - heart and brain

eye - liver

Basal cell carcinoma (BCC)

- most common

- increase incidence with age and UV exposure

- slow growing - due to high rate of apoptosis

- grows radially

- rarely metastasizes

Squamous cell carcinoma

- common

- increase incidence with age and UV exposure

- grow a bit faster then BCC

- usually diagnosed prior to metastasis

Graves disease and causes

Graves disease is an autoimmune disease that causes hyperthyroidism. The hypothalamus produces thyrotropic-releasing hormone (TRH) which stimulates the anterior pituitary gland to produce thyroid stimulating hormone (TSH). TSH stimulates the thyroid to produce T3 and T4 which work to reduce TSH and TRH through a negative feedback loop. In Grave's disease, B cells produce plasma cells that act the same as TSH (they are TSH mimics). This results in very low levels of TSH and TRH, but T3 and T4 are still produced by the thyroid

symptoms of graves disease

- increased metabolic weight

- heat intolerance

- weight loss

- anxiety

- fine tremor

- proptosis

functional tumour & the

possible implications for hormone levels

Functional tumour: well differentiated and they still produce hormone but in an uncontrolled way - independent of stimulation - excess of that hormone

well-differentiated tumour pituitary adenomas

- secrete the hormone usually produced by that cell but in excess

- insensitive to usual regulations.

- tumour increases in size - cause atrophy to the normal pituitary gland = hormonal deficiency of the other hormone types secreted by the gland

Poorly-differentiated tumours pituitary adenomas

- dont secrete hormones

- cause atrophy of surrounding tissue

GH excess in adults and children

adults - acromegaly

children - gigantism

What is Cushing's syndrome and how may it be caused

exposure to high levels of cortisol for long periods of time ....................................................................... cause

- excess cortisol

- prolonged use of corticosteroids/glucocorticoids

- chronic stress

- ACTH ............................................................................................. symptoms

- increased fat deposition in trunk and face

- muscle atrophy + weakness

- osteoporosis

- thinning of skin

- poor wound healing

- hyperglycaemia/hypertension

- depression

type 1 diabetes aetiologies

- autoimmune disease

- no beta cells = no insulin production

- target tissue cant take up glucose without insulin - so starving - use alternate fuel source

- blood sugar is high as target tissue cant use it

type 2 diabetes aetiologies

- insulin insensitive

- target tissues have enough blood glucose to sustain but they do not take up enough glucose to reduce the serum levels to within a physiological range

cause

- environmental

- overweight or central adiposity

- inactive/sedentary

treatment: weight loss

initial presentations of type 1 diabetes and treatment

- present in childhood that are normal or underweight

- frequently an acute emergency from sever hyperglycaemia

- lead to altered consciousness and coma

treatment: insulin injections

initial presentations of type 2 diabetes and treatment

- polyphagia, polydipsia and polyuria

- overweight and sedentary

- neuropathy - loss of sensation or chronic pain

treatment: weight loss or later insulin injections

List other pathologies that are more frequently observed in diabetic patients

- ischaemic heart disease

- cerebrovascular disease

- peripheral vascular disease

- neuropathy

- nephropathy

- retinopathy

- glaucoma

- cataracts

- infections

What is the purpose of myelin & an example of a demyelinating disease that affects the CNS

- Myelin insulates the nerve/axon allows the single to be fast to get through

- Removing myelin sheath or demyelinating slows the single down until it is lost

- MS disease

examples of SOL

- tumours

- haematomas

- oedema/swelling

- abscesses

- hydrocephalus

- aneurysm

why are SOL (space occupying lesions) bad

- skull is closed system and filled with CSF

- something slowly introduced - brain atrophy but this is limited

- leads to rise in ICP and brain herniation

List age-related diseases of the CNS

- cerebrovascular disease

strokes

- glioblastoma

- Parkinson's

- alzheimer

- carcinomas

What occurs on a cellular level when tissues undergo atrophy

autophagy

apotosis

causes of brain atrophy

- age (subdural hematomas)

- alcohol/drug abuse

-slow SOL

atherosclerosis

- hypertension

- smoking

- hyperlipidaemia

- diabetes

What determines whether atrophy or brain herniation occurs in response to a SOL

speed

slow - adapts through atrophy

fast - herniation

Meningioma - benign or malignant?

benign but deadly

most common malignant tumour in CNS

children - astrocytoma

adults

- glioblastoma

- metastatic cancer (carcinoma or melanoma)

What occurs in the normal brain tissue surrounding the tumour and are these cellular changes reversible

tumours cause

- secondary oedema

- rise in ICP

occurs gradual - atrophy of brain - apoptosis

not reversible

complications occur when there is necrosis and bleeding within brain tumour

- sudden rise in ICP

- brain herniation

What intracranial pathology might be expected from a case of trauma to the head

epidural, subdural, subarachnoird haematoma, intracerebral haemorrhage, cerebral contusion and laceration, concussion, coup-countercoup injury

epidural haemorrhages aetiology, pathogenesis, outcomes

- rupture of dural arteries from trauma

- high arterial pressure results in rapid accumulation of blood/haematoma between skull and dura

outcome

- surgery, as ICP is increasing and predispose in herniation and death

Subdural haematomas aetiology, pathogenesis, outcomes

- tearing of the bridging veins between dura and arachnoid layers

- tear from displacement of the skull

- brain moves within the CSF easily

- old people and people with atrophy greatest risk

outcomes

- progress slowly - vague symptoms

- lysis and organisation

- large tears = rapid rise in ICP and brain herniation

subarachnoid haemorrhage aetiology, pathogenesis, outcomes

- result of trauma = arterial haemorrhage from congenital aneurysm

outcome

- rapid rise in ICP due to rapidly accumulating haematoma

what is a stroke

Necrosis occurring in the brain from ischemia or haemorrhage resulting in altered brain function

acute conditions that atherosclerosis of the carotid and cerebral arteries can cause

- thrombus - ischemia - stoke

- embolus - ischemia stroke

- aneurysm - haemorrhagic stroke, herniation, death

chronic conditions that atherosclerosis of the carotid and cerebral arteries can cause

- atherosclerosis = atrophy

- loss of functional tissue = vascular dementia

- sub-dural haematomas

- swelling and bleeding of plaque - ischemia - TIA = atrophy and dementia

4 ways brain and meninges become infected

1. trauma/surgery

2. blood

3. extension from local sites

4. PNS

anatomical difference between encephalitis and meningitis

encephalitis - brain tissue

meningitis - within the meningeal layers

viral meningitis

- CSF normal glucose

- may contain lymphocytes = slight increase in protein

- intracellular

- good prognosis

Bacerial meningitis

CSF

- cloudy

- increased protein

- reduced glucose

- extracellular - will attract an acute response

prognosis - bad

- increased ICP

- brain herniation = death

List the main types of fractures

- simple

- compound

- comminuted (open)

- greenstick

- pathologic fractures

impaired healing in fractures

- movement

- interposed soft tissue

- infection

- gross misalignment

- bone disease

- nutrition

stages of healing in fractures

1. haematoma - acute inflammatory

2. soft callus - granulation tissue

3. hard callus - mineralisation

4. remodelling

factors for attaining peak bone mass

- physical activity

- genetics

- hormones

- nutrition

List the risk factors for the development of osteoporosis,

consequences and how it can be reduced

- Aging

- Amenorrhea

- Use of glucocorticoids and corticosteroids

- Menopause

- Sarcopenia

- graves

- cushings

Reduce

- Resistance training

- Hormone replacement at menopause

List the tumours that occur in the skeletal system

Benign

- chondroma

- osteoma

malignant

- osteosarcoma

- chondrosarcoma

- ewings tumour

healthy kidneys and bone health

- activate vitamin D

-gut to absorb dietary calcium

- regulate plasma levels of calcium & phosphate

- response PTH - the healthy kidneys activate more vitamin D = increase dietary calcium

- healthy kidneys excrete phosphate (from the blood into the filtrate/urine) & reabsorb calcium from the filtrate = increasing serum/blood calcium levels = reduces the release of PTH

bad

- low blood calcium levels - default is for calcium to be filtered out by the kidney + phosphate is retained

- low serum calcium levels = PTH is released & stimulates osteoclasts to resorb bone = release calcium & phosphate blood

2 complications of Pagets disease

- deformed bone - weight bearing in weak bones

- pathologic fracture - weak bone less resistant to external forces

what can predispose pathologic fracture

- pagets disease

- osteoporosis

- osteomalacia

- renal failure

- tumours

- osteomyelitis

- arthritis

what form of cell death is occurring in osteoporosis

apotosis

why is osteosarcoma common in young people

- bone is actively growing

- occur in the actively growing epiphyseal plates = increased proliferation = cancer

how does acute osteomyelitis become chronic

- if bacteria stimulus remains = acute to chronic

- bone fragments = necrotic - their blood supply is compromised by infection

- dead pieces of bone = foreign bodies = inflammation

What main cellular changes distinguish acute from chronic inflammation for bones

lymphocytes

Gout aetiologies, pathogenesis, typical joints affected, & populations at risk

- systemic metabolic disorder

- Hyperuricaemia (vulnerable)

- Monosodium urate crystals in joints & soft tissues = pain and inflammation

- age

- big toe men

- hands women

osteoarthritis aetiologies, pathogenesis, typical joints affected, & populations at risk

- wear and tear - loss of cartilage

- swelling to surrounding tissue - pain

- little inflammation

- weight bearing joints

- elderly, overweight, sports

rheumatoid arthritis aetiologies, pathogenesis, typical joints affected, & populations at risk

- autoimmune disease

- destruction of any synovial joint and causes systemic inflammation and irreversible joint deformation

- women more then men

- middle age

- affects smaller joints

main tumours in males and females reproductive system

Females

Stratified squamous- squamous cell carcinoma - vulva, penis, cervix

Uterus

Endometrium - glandular epithelium - adenoma, adenocarcinoma

Myometrium - leiomyoma, leiomyosarcoma

Ovaries - germ cells, teratoma - teratocarcinoma

Surface epithelium - secretary epithelium - grows as a cyst - Cystadenoma - cystcarcinoma

Breast- glandular epithelium - adenocarcinoma

Males

Prostate -glandular epithelium - adenoma, adenocarcinoma

Testes- teratoma

causes of PID

gonorrhea and chlamydia

infection ascends = PID

consequences of PID

Ectopic pregnancy

Female infertility

Pain

Infection into peritoneum and blood