Pathology Review-Term3

As is our Pathology, so is our Practice.

-- Sir William Osler, M.D. (Father of Modern Medicine & Founding professor of John Hopkins,

developed first residency program for physicians.)

Pathology: The science of medicine !

CPC31: Week Overview2013 Term 3 CPC 1 Title: Endocrine 1/1 Thyroid

System: EndocrineAim: To educate students in Clinical, pathology & population

study of patients with Endocrine disorders (using example of thyroid disorder).

Learning Outcomes:Students will be able

to

1. Demonstrate an ability to take a focused History & carry out a focused clinical examination of patients with neck swelling and systemic symptoms

2. Describe the Pathophysiology of common endocrine disorders.

3. Describe the pathophysiology of thyroid disorders.4. Outline the basic sciences relating to

hypothalamic/pituitary/thyroid axis; thyroid function testing; role of anti thyroid antibodies in differentiating thyroid disease

5. Outline first line treatment of thyroid disorders.

Graves, Hashimoto, MNG, Cancer.

Cushings, Addisons, PheochromocytomaAdenoma, carcinoma

Hyper/Hypo parathyroidism

Head injury, infections, Inflammations & TumoursCentral Diabetes Insipidus, Hypogonadism

Adenoma, Ischemia (Sheehans),Diabetes insipidus,

Atrophy / hyperfunction

DIABETESAdenoma, carcinoma

Tumours, Cysts, Atrophy, Dysfunction

Tumours, Cysts, Atrophy, Dysfunction

Tumours, Cysts,

Hypothal: Tertiary

Pituitary: Secondary

Gland: Primary

Hyper – Thyroidism - Hypo • Hyper-Metabolic… • Hypo-Metabolic…

Nontoxic-Multi Nodular Goitre.

A: conspicuous neck mass. B: Coronal section showing numerous irregular nodules, some with hemorrhage. C: Microscopy: variation in the size of the follicles.

Note: TSH, T3,T4 Normal

(Euthyroid)

Carcinoma of ThyroidType (%) age spread Prognosis

Papillary 60-70 young adults 20-40 (<45y)

Lymphatic, to local nodes

Excellent

Follicular 20-25 Young-middle 40-50 (>45)

Blood stream, especially to bone

Good with radio-iodine therapy.

Psammoma Body

Papillary Carcinoma:

SIADH: Sy of Inappropriate ADH secretion

SIADH

• Too Much ADH• Water Intoxication• Low Serum Sodium• Low Serum Osmolality• High Urine Osmolality

Diabetes Insipitus

• Too Little ADH• Dehydration• High Serum Sodium• High Serum Osmolality• Low Urine Osmolality

ExcessAndrogens

Adrenal Glands:• Cortex (glands)

– Glomerulosa - Mineralocorticoids– Fasciculata - Glucocorticoids– Reticularis – Gonadal hormones

• Medulla (Neural)– Chromaffin cells & sympathetic nerve endings - Noradrenaline

Adrenaline (epinephrine)• Pathology: common.

– Pheochromocytoma – medulla hypertension.– Addison’s disease*– Cushing’s syndrome* & Disease*.– Conn’s syndrome*.– Congenital adrenal hyperplasia(21-hydroxylase deficiency)

Precocious puberty

Pheochromocytoma:• Tumor of medullary Chromaffin cells.• Increased catecholamines• Secondary hypertension.• Young age.• May be familial (MEN syndrome).• Increased Urinary VMA

Waterhouse-Friderichsen Sy• Acute hemorrhagic necrosis (apoplexy).• Shock/Septicemia• Lack of aldosterone• Salt & water loss• Hypovolemic shock• Hypoglycemia.

The adrenals from a child dying of meningococcal septicaemia are destroyed by haemorrhage.

K K

Addison’s Disease:• Chronic adrenal insufficiency.• anorexia, weight loss, vomiting • Weakness, lethargy, hypotension • skin pigmentation • hyponatraemia with hyperkalaemia • chronic dehydration, sexual dysfunction.• Low plasma cortisol.• ACTH high (primary) or low (sec)

• Autoimmune 70%, • Infections (TB, fungal), tumours,

Type I MEN Type II

MEN - Gene - RET

Education is what remains after we have forgotten all the facts taught in the class!--

CPC32: Week Overview2013 Term 3 CPC 2 Endocrine 2 - Diabetes

System: EndocrineAim: To educate students in: Clinical, Pathology & population

study of patients with Diabetes MellitusLearning

OutcomesStudents will be

able to

1. Demonstrate an ability to carry out a focused History & clinical examination of patients with diabetes.

2. Describe the pathophysiology of Diabetes Mellitus Types 1 + 2 and their complications.

3. Outline the Basic sciences relating to endocrine function.

4. Explain the abnormalities of Blood supply common in diabetic patients including - ischaemia, infarction & necrosis.

5. Outline the epidemiology and aetiology of Diabetes Mellitus in Australia and world wide.

6. Outline first-line management and demonstrate an understanding of the process of care of a diabetic patient.

II NIDDMII GDMI IDDM

Sec IDDMSec IDDM

I LADASec IDDM

I IDDMLADA

MODY

Most likely .. What type of DM ?

1. 56 year male obese2. 30 year female following pregnancy3. 8 year old boy, poor growth, DKA.4. 24 year female Cushing’s sy5. 68 Year male following Ca. pancreas.6. 32 male, DM, BMI 18, Anti-GAD +ve.7. 34 year male, extensive tuberculosis.8. 12 year old female following viral fever9. 41y DM2, BMI 17.1, HbA1c 14.1, DKA10.15y male, BMI 16.2, recurrent infect.

DM Questions• Definition? types common? Diagnosis?• Primary & Sec? Congenital? Gestational?• Monogenic? MODY, LADA, drugs?• List functions of Insulin? Antagonists?• Etiology & Pathogenesis of Type 1 & 2.• Stages of DM & their pathological basis?• Obesity & Insulin resistance *

– FFAs, PKC, Adipkines, PPARγ– Inflammation & Insulin resistance.

• Mechanism of β cell destruction type 1, 2.• Islet Amyloid PolyPeptide (IAPP)?

DM Questions• MODY & LADA – pathogenesis, subtypes.• Pathogenesis of Complications:

– Mechanism: AGEs, Activate of PKC, & Polyols.– Infections – common & pathogenesis.– Foot ulcer, Retinopathy (prol & non-prol), – Neuropathy? Central, peripheral, autonomic…– Difference Angiopathy Micro & Macro? MI, Stroke.– Diabetic Nephropathy – albuminuria, KW lesion,

Papillary Necrosis, Pyelonephritis, CRF.– Hypertension, Cataract,

• Metabolic: Diabetic Coma, DKA, HONK **

InsulinAnabolic Steroid

GLUT4 *

only these tissues….!

Obesity & Insulin

resistance.

Diabetes is a state of inflammation

Peripheral Res.

GIP : glucose-dependent insulinotropic polypeptide (GIP)GLP-1: glucagon-like peptide-1 (GLP-1)DPP 4: enzyme dipeptidyl peptidase-4 (DPP-4) – breaks down GIP & GLP-1

Insulin Resistance:

JCU Research…!

Diabetes Classification: (not a single disease)

– Type I – IDDM / Juvenile – 5-10%.– Type II – NIDDM /Adult onset – 90-95%.– MODY – 5% Maturity Onset Diabetes of Youth

• Genetic, sub types MODY 1–6 (3 & 2 common),– LADA – Latent Autoimmune Diabetes in Adults (LADA)– Gestational Diabetes Mellitus.– Other. (neonatal diabetes, – Insulin gene defects)

Endocrinopathy, Downs Sy.

– Excess hyperglycemic stimulus (drugs & disease).• Cushings, Phaeochromocytoma, acromegaly, Steroid therapy.

– Beta cell destruction:• Pancreatitis/tumors/Hemochromatosis – Bronze diabetes.• Infectious – congenital rubella, CMV, TB,

Pathogenesis of Type I DM

Genetic HLA-DR3/4

EnvironmentViral infe..?

Insulin deficiency

Autoimmune InsulitisAb to ß cells/insulin

ß cell Destruction

Secondary DMInflammation,

Tumor, InfectionTrauma

Pancreatitis

Antibodies:Islet cell Ab - ICA

Insulin Auto Ab - IAAGlut. Acid Decarb - GAD65

Type-1 clinical course

Type IIPathogenesis

Relative

Insulin Def.β cell

dysfunction

?

Β cell ExhaustionIDDM

Progression of Type II

Years ..

Type-I Type-II

Insulitis:Lymphocytic infiltrate within islets.

Islet Hyalinization:Central hyaline deposits replacing

dead beta cells(only in late stage…!)

DM:Complications:

DM Microangiopathy – pathogenesis

Normal

Diabetic

Glucose Glycosylation BM damage leak ‘AGE’ deposition

PATHOGENESIS OF DM COMPLICATIONS:1. Chronic Hyperglycemia.2. Glycosylation of BV B. membrane 3. Leakage of proteins, excess BM matrix.4. Narrow, thick, fragile, Leaky BV + Inflam.5. Leakage of LDL, protein, angiogenesis.

• Ischemia• Proteinuria (kidney)• Micro Aneurysms (retina)• Atherosclerosis.

“A man must be big enough to admit his mistakes, smart enough to profit from them, and strong enough to correct them!”

--John C. Maxwell

CPC33: Week over veiw2013 Term 3 CPC 3 Title: Neurology 1 – Head injury, Stroke.

System: CNS-NeurologyAim: To educate students in:

Clinical, Pathology & population study of patients with Head Injury, including non traumatic brain injury & stroke.

Learning Outcomes:

Students will be able to

1. Demonstrate an ability to take a focused history & perform a relevant and focused clinical examination of patients with loss of consciousness/alteration in neurological function

2. Describe the Pathophysiology of cerebrovascular accidents.3. State the Pathophysiology of hypertension (review).4. Recall the components of Basic sciences relating to function of the

brain. 5. Define the Epidemiology and Pathology of cerebrovascular disease

(stroke).6. Describe the Epidemiology of neurological diseases in Australia and

world wide.7. Define the first line management of patients with impaired Glasgow

Coma Scores8. Demonstrate an understanding of the complications of intra-cerebral

events

Learning Objectives:

• CNS: Functional Anatomy, Physiology & Blood supply – Revision

• Stroke: Definition, types, etiology, clinical features, complications.• Brain Ischemia: TIA, Embolic, Hemorrhagic & Ischemic. • Healing in brain tissue – liquifactive necrosis, gliosis.

• Head Injury: types, pathophysiology, clinical & complications.• Concussion, Contusion, Laceration.• Hemorrhage: Epidural, Subdural, Subarachnoid, intra cerebral.• Brain herniation – types & clinical features. Subfalcine, uncal, tonsillar.

• Hypertension: Pathophysiology, diagnosis & Complications *Self Study • Hypertension & CNS damage, Hypertensive encephalopathy.• Epilepsy: Overview, types, pathophysiology, Clinical *Self Study

Anatomy – Stroke.

Pathogenesis

Berry Aneurysm

Incidence

CNS - Blood supply MCA - Common site of Hem

Blunt Head Injury: • Primary Injury:

– Coup & Contra-Coup– Focal damage-concussion, contusion, – Diffuse axonal injury.

• Secondary Injury:– Concussion– Epidural/subdural Hematoma– Oedema– Infection

• Post Traumatic Complications:– Epilepsy– Dementia– Coma.

Coup

Contre Coup

Epidural - Hematoma - Subdural

Sub arachnoidHptn, Atherosclerosis

Old age, fall, delayed symptoms

Dura fixed to skull

Pia fixed to brain

Arachnoid

Subarachnoid Hem: alone is not trauma..!

Think of:• Hypertension, • Berry aneurysm, • Atherosclerosis.

Aetiology:Atherosclerosis – most common.Hypertension, smoking, diabetes.Heart disease – Atrial fibrillationOther:

Trauma – fat embolismTumor, InfectionCaissons disease – Bends *Pacific.

Hypertensive Intracerebral Hem: Sites

1. Putamen-Claustrum2. Cerebral white matter3. Thalamus4. Pons5. Cerebellum

55% - MCA deep br.15101010

MCA stroke.

Left (Dominant) Hemisphere Stroke: Clinical

• Aphasia • Right hemiparesis • Right-sided sensory loss • Right visual field defect • Poor right conjugate gaze • Dysarthria • Difficulty reading, writing, or

calculating

Diagnosis: Recent cerebral infarction in left MCA distribution.Left cerebral hemisphere shows swelling with compression of the lateral ventricle mainly in the frontal area, due to recent infarct in the Middle Cerebral Artery (MCA) distribution. The brain in the MCA area shows discoloration of the cortex and also blurring between the cortex and white matter.

ACA stroke.• Paralysis of contralateral foot

and leg• Sensory loss over toes, foot

and leg• Impairment of gait and stance• Abulia (slowness and

prolonged delays to perform acts)

• Flat affect, lack of spontaneity, slowness, distractibility

• Cognitive impairment, such as perseveration and amnesia

• Urinary incontinenceWikipedia: GNU Free Documentation license

PCA stroke.Peripheral (cortical)• Homonymous hemianopia• Memory deficits• Perseveration (repeat response)• Several visual deficits (cortical

blindness, lack of depth perception, hallucinations)

Central (penetrating)• Thalamus - contralateral sensory loss,

spontaneous pain, mild hemi• Cerebral peduncle - CN III palsy with

contralateral hemiplegia• Brain stem - CN palsies, nystagmus,

pupillary abnormalities

Wikipedia: GNU Free Documentation license

Infarct Pathogenesis:• hypoxia/anoxia.• Na/K pump block. • Calcium influx.• Red neuron, vacuolation.• Cell death, karyorrhexis.• Inflam- neutrophils, hem.• Lympho, Macrophages.• Liquefaction cavity• Peripheral Gliosis (astrocytes)

Hours

1-day

3-day

1 wk.

>4wk

CNS AV Malformations:

• Many types:– AV Malformation *– Cavernous angioma– Telangiectasia– Venous angioma

• Cause of Seizure disorders & hemorrhage.

• Most common congenital vascular malformation.

• Typically located in the outer cerebral cortex underlying white matter.

Hypertension Stroke:

Hemorrhagic stroke (new) & Lacunar infarct (old)

Central Pontine Hem – Herniation, IC pressure

Our greatest glory is not in never falling, but in rising every time

we fall.

-- Confucius

CPC34: Week over view2013 Term 3 CPC

4Title: Neurology 2

System: NeurologyAim: To educate students in:

Clinical, Pathology & population study of patients with dementiaLearning

Outcomes:(Students will be

able to)

1. Demonstrate an ability to take a relevant and focused history and carry out a relevant clinical examination of patients with dementia.

2. Carry out a competent physical examination of neurological system.3. Describe the Pathophysiology & Pathology of common causes of

dementia (Alzheimer’s Disease, multi infarct dementia)4. Recognsise rare neurological causes of dementia (Huntington’s

disease, CJD, HIV).5. Outline the basic sciences relating to structure and function of the

brain. 6. Describe the difference between age associated memory

impairment, mild cognitive impairment and Alzheimer’s disease7. Outline the epidemiology of Alzheimer’s disease and other causes

of dementia in Australia.8. Explain the first line management of common causes of dementia 9. Outline ethical dilemmas in caring for patients with dementia

Broca’s area - Cingulate and Parahippocampal gyri.

Hippocampus: where short-term memories are converted to long-term memories

Thalamus: receives sensory and limbic information and sends to cerebral cortex (cognition)

Limbic system: controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex)

51

CNS Degenerations: Classification

• Neuronal Degenerations.– Primary Degenerations:

• Global – Alzheimer, Lewy body, Fronto-temporal• Selective/System – Parkinsons, Huntingtons, MND

– Secondary Degenerations:• Toxic, metabolic(storage), infections, nutritional.• Alcohol & B12 def.

• Myelin Degenerations:– Demyelinating Disorders - Multiple sclerosis– Dysmylinating disorders – Leukodystrophies.

52• Cortical Atrophy

• Intraneuronal Neurofibrillary tangles

• Interstitial amyloid Neuritic plaques• Loss of neurons with gliosis.

Alzheimers Disease: MorphologyGross Microscopy

53

Pick’s Disease:

• Severe, 40-65y, Rare. • knife blade atrophy of

Frontal & temporal lobe Progressive aphasia / language dysfunction

• Behaviour & personality change.

• Preserved memory.• Micro: Neurons with

round intracytoplasmic Pick’s bodies (tau protein)

54

Diffuse Lewy body Dementia: DLD• 10-15% of Parkinsons with

dementia within a year of motor symptoms.

• impaired memory of recent events, confusion, language problems. (Alzheimer)

• Dementia + visual Hallucinations.

• Lewy body (α-synuclein) in many part of cortex & substantia nigra (global)

• Atrophy of cortex like AD.• Rapidly progressive – early

death.

cortical Lewy bodies (α-synuclein) special stain.

Parkinson’s:• "shaking palsy" • Parkinsonism: Clinical sy.

– Drugs: dopamine antagonists– Toxins: MPTP(heroin), – Diseases: Multiple system atrophy, Post encephalitic.

• Parkinson’s disease – Primary atrophy of substantia nigra. Dopaminergic nerves with α-synuclein - Lewy body.

• Clinical features: – Adults (45-60y), tremor, bradykinesia & rigidity – Diminished facial expressions, stooped posture, – Slow voluntary movements, festinating gait, & fine rolling resting

tremors. Dementia in some cases.– When dementia arises within 1 year of the onset of motor

symptoms, it is referred to Lewy body dementia (LBD).

56

Pathology of Parkinson’s disease:• Gross: Loss of

pigment in substantia nigra.

• Neuronal loss, degeneration,

• Loss of neurons replaced by gliosis (microglia)

• Loss of neuromelanin.• Neuronal

degeneration• Reactive gliosis.• Lewy bodies (α-

synuclein) in neurons.

Parkinson

Normal

L

57

Huntington’s

• Dementia, depression, choreiform movement (Jerking dementia)

• 5th decade. Autosomal dom.• Huntington gene on 4p –

Huntingtin.• Excess CAG tandem

repeats = severity.

Striatal atrophy

Atrophy of caudate & putamen (striatum) Compensatory hydrocephalus of lateral ventricles*.

58

Metabolic CNS Disorders: Alcohol• Vit. B1 (thiamine) def.• In Chronic alcoholics,

malabsorption syndromes.• Wernicke encephalopathy

ataxia, confusion, double vision…

• Korsakoff psychosis: memory loss with confabulations. Hallucinations.

• Cortical atrophy.• Central pontine myelinolysis. • Atrophy of vermis of the

cerebellum.

59

Wernicke's encephalopathy:

Recurrent petechial hemorrhages in the hypothalamus, mamillary bodies with atrophy. Central pontine myelinolysis.

60

Vitamin Def & Neuropathy:

• B1 Wernicke-Korsakoff syndrome

• B2 Peripheral neuropathy,

ataxia,dementia• B6 Convulsions in infants

• B12 - SCDC.• C Scurvy

• E Weakness, sensory loss, ataxia, nystagmus

61

Multiple Sclerosis:• Common 1:1000, adults,

females 2:1, HLA DR2, <50y.• Autoimmune (Gen+Env+AI)• Episodes of Limb Weakness,

paraesthesia.• Relapsing & remitting.• Progressive death in years.• Multiple soft pink plaques of

demyelination- periventricular.• Inflammation, perivascular T

lymphocytes & plasma cells.• CSF - oligoclonal IgG.• Reactive gliosis.

62

Multiple Sclerosis: Demyelinated plaques

Microscopy showed loss of myelination with many lipid macrophages around BV.

63

ALS: Amyotrophic Lateral Sclerosis

• Also known as Lou Gehrig's disease, is the most common type of Motor Neurone Disease (MND).

• Genetic: Mutations in SOD1 gene on Chromosome 21.

• Progressive neuron loss.• Middle age, men, sporadic common,

Familial 10% • Muscle weakness, fasciculations,

spasticity, Sensation normal.• Degeneration of LMN tracts in the

lateral portion of the spinal cord ("lateral sclerosis"). and of UMN - Betz cells in the motor cortex.

Degeneration of lateral and ventral corticospinal tracts (myelin stain).

MND subtypes:• Amyotrophic Lateral Sclerosis*• Progressive muscle atrophy (LMN) • Primary lateral sclerosis (UMN)• Progressive bulbar palsy

64

Dementia Cases:49y woman, chronic cognitive difficulty, irritability, depression, poor movememnts, no significant memory loss, muscle rigidity, wide gait, choriform movements of trunk & limbs. (Father & many of relatives had involuntary movements.)

74y man, mild cognitive decline, slow gait, depression, resting tremors, visual hallucinations, episodes of “absent” “confused” MMSE 27/30, ACE-R score 78/100. Rigid muscles,

Huntington’s Disease

Diffuse Lewy body Dementia

Parkinson’s with Dementia

75y man, rapid decline in cognitive function with fluctuations, MMSE 22/30. Ten point clock face drawing test - 0. Day time sleepiness. Apathy, visual and auditory hallucinations.

65

Dementia Cases:56y man, progressive speech difficulty 2y. Slow to respond, paucity of words. Lack of judgement, disorganized, aggression, impulsive. Good memory. Left hand weakness, progressive motor weakness. MMSE 27/30. FH of dementia.

Dementia pugillistica.

Amyotropic Lateral Sclerosis

59y professional foot ball player. Progressive dementia & tremor.

Fronto-Temporal / Pick’s

58y man, mild cognitive impairment, weakness of distal limbs, loss of muscle mass, fasciculations, rigidity. Babinski sign +ve. Recurrent respiratory infections.

67y man, previously healthy, 3m h/o rapid dementia, weakness of hands & fingers, insomnia, irritability, inability to find his way home. visual hallucinations and tremor, speech difficulty, admitted with Gen. seizure.

CJD – Mad Cow Disease

The only real mistake is the one, from which we learn nothing!

JOHN POWELL:

Alzheimers Pathogenesis: YouTube

CPC35: Week over view2013 Term 3

CPC 5Title: Neurology 3

System: NeurologicalAim: To train students in :

History taking + clinical examination of post ictal/acutely unwell patient; pathology of brain tumours; pathology of meningitis; pathology of epilepsy; process of care + population health especially rural and remote

Learning Outcomes

Students will be able to

1. Demonstrate an ability to take a relevant and focused History & clinical carry out a relevant examination of patients after a witnessed seizure

2. Describe the Pathophysiology of primary and secondary brain tumours; meningitis; epilepsy

3. Recall the relevant basic sciences including normal anatomy and blood supply of the brain

4. Recall the differential diagnoses for a patient with a first fit5. Describe first line management in a patient with a first fit or

altered level of consciousness.

Scenario: MeningitisFever, Headache, neck stiff, Brudzinski sign, Kernig sign, CSF…

Scenario: Brain TumorCrescendo Chronic Morning headache*, Seizures, localizing signs

Scenario: Epilepsy:Negative signs, chronic/recurrent, family / past history.

CNS Infections - Overview• Meningitis – commonest.• Meningo-encephalitis – combined.• Infections of Dura – Pachymeningitis – rare.• Arachnoid – Leptomeningitis – common.• Bacterial, Viral, fungal, TB, (Chem, Ca, drugs)

Subdural Abscess - Sinusitis

Lepto - Meningitis

Cerebrum - normal

Encephalitis

Septic Meningitis: common causesAge Causes

Neonates Escherichia coli, group B streptococci.Children / Adolescents

N. meningitidis, S. pneumoniae, TB

Adults S. pneumoniae, Listeria monocytogenes, TB, crypto,

Asymptomatic carriers nasal spread blood CNS. Headache, photophobia, irritability, clouding of

consciousness & neck stiffness. Limited to lepto-meninges - Acute, inflam, pus. Both cranial and spinal. Cloudy, high protein, low sugar, neutrophils, + Bacteria.

Septic Meningitis-Microscopy

Septic Meningitis-Spinal fluid

Normal Septic Gram +ve Diplococci+Neutrophils

Contraindications for CSF examination:• Increased intracranial pressure.• CNS infarctions (A),

Hydrocephalus (B) abscess (C) or edema(D).

Viral Meningitis:

• Acute, Self limiting, Less severe than bacterial.• Clear CSF, sugar normal, lymphocytes, protein.• Cerebral edema, perivascular lymphocyte cuffing.• Reactive microglial nodules.• Arbovirus*, Herpes, Varicella Zoster, CMV, Polio, Rabies.

Perivascular cuffs of lymphocytes and Microglial nodules

CSF-ExaminationCells Protein Glucose Appearance

0-4 lympho 0.1-0.4(n) 2.7-4.0 (n) Clear colorless

> Poly High Low Turbid

> Lymph High normal Clear

> lymph High Low Opalescent (cob-web)

Norm

Septic

Viral

TB

10 – 10 – 10minutes months

years

"I wasn't living my life. My life was living me. I realised I made many of my decisions without thinking their consequences… “I realised all I really had to do to reclaim my life was to Start making decisions by considering their consequences in the immediate present, near term and distant future.. i.e . In ten minutes, in ten months and in ten years”.

-- The 10-10-10 rule, Suzy Welch.

The 10-10-10 rule…Think about effect of your decision in….

Most common CNS Tumors:

children

Adults(Glioblastoma)

MeningiomaDural Venus sinus

Capsulated,spindle cells in whorls and psammoma bodies (common type).

Astrocytomas

• Adults:–Commonest 80%, Cerebral.–Low Gr: Solid, Fibrillary. –High Gr: glioblastoma multiforme

Varigated, Hemorrhagic - Malignant,.• Children:

–Cystic, Low grade*, Pilocytic– Infratentorial (Cerebellum),

Astrocytomas - Glioma

• Adults:– Commonest 80%, Cerebral.– Low Gr: Solid, Fibrillary glioma – High Gr: glioblastoma multiforme Varigated,

Hemorrhagic - Malignant,.• Children:

– Cystic, Low grade*, Pilocytic– Infratentorial (Cerebellum),

mutations of the metabolic enzyme Isocitrate DeHydrogenase (IDH1 and IDH2) are common in lower-grade astrocytomas. As a result, immunostaining for the mutated form of IDH1 has become an important diagnostic tool for low grade gliomas.

Glioma/GBM:• Commonest • Low high grade.• cerebral supratentorial.• Chromosome 10 (80%)• Most GBMs have lost one

entire copy of C – 10• Microscopy: • Pleomorphic astrocytes,

Necrosis, palisading.

Necrosis

Common CNS Herniations:• Subfalcine: common,

Headache contralateral leg weakness.

• Transtentorial: occulomotor (CN III) paresis (ipsilateral dilated pupil, abnormal EOM's), contralateral hemiparesion.

• Tonsillar: Obtundation.

Why pupils dilate? Sympathetic / parasympathetic Balance.

“Sympathetic system shows sympathy to your dress!”

One of the first duties of the physician is to educate the

masses not to take medicine!

-- Sir William Osler (1849 - 1919), Aphorisms from his Bedside Teachings (1961) p. 105

CPC36: Week over view2013 Term 3 CPC 6 Title: Infections & PUO

System: Infectious diseaseAim: Develop understanding pathology & clinical diagnosis of

patient with pyrexia of unknown originLearning Outcomes:Students will be able

to

1. Demonstrate competency in taking a focused History taking & clinical examination of patients with pyrexia

2. Demonstrate relevant focused physical examination of all systems relevant to a patient with PUO

3. Demonstrate competency in formulating the differential diagnoses of patients with PUO

4. Outline the Management of PUO5. Outline the Basic sciences applicable to PUO including

– Infection & Immunity.6. Describe the pathology of arboviruses including

transmission of disease. (Tropical diseases)

Viral Infections - Bacterial• Infectious Mono. • CMV• HIV• Hepatitis B• Herpes• Viral exanthema-

mumps etc.• Ross River Fever• Dengue• Australian Encephalitis.

• TB• Leptospirosis• Brucellosis• Q Fever• Relapsing fever• Nocardiosis• Typhoid

Tropical Infections• Ross River Fever• Dengue, Leptospirosis• Malaria, Q fever, • Melioidosis.

Major Arboviruses:• Alphaviruses

– Ross River Virus (RRV) – epidemic arthritis– Barmah Forest Fever– Equine Encephalitis – many types.

• Flaviviruses– Dengue – Hemorrhagic fever.– Murray Valley Encephalitis – meningitis like.– Japanese encephalitis – Yellow fever

• Bunyaviruses– LaCrosse encephalitis – Reo viruses – Colorado tick fever

The major arboviruses of concern in Australia are:

• Dengue • Ross River Virus • Barmah Forest Virus • Japanese Encephalitis • Murray Valley Encephalitis Ref: UQ.edu.au

Ross River Fever - Symptoms:• Fever • Rash• Arthritis• Fatigue• Headache• Lymphnode

enlargement.

Warning Signs for Dengue Shock

When Patients Develop DSS:• 3 to 6 days after onset

of symptoms

When Patients Develop DSS:• 3 to 6 days after onset

of symptoms

Initial Warning Signals:• Disappearance of

fever• Drop in platelets• Increase in

hematocrit

Initial Warning Signals:• Disappearance of

fever• Drop in platelets• Increase in

hematocrit

Alarm Signals:• Severe abdominal

pain• Prolonged vomiting• Fever to hypothermia• Change in level of consciousness

Alarm Signals:• Severe abdominal

pain• Prolonged vomiting• Fever to hypothermia• Change in level of consciousness

Four Criteria for DHF:• Fever• Hemorrhagic

manifestations• Excessive capillary

permeability• 100,000/mm3 platelets

Four Criteria for DHF:• Fever• Hemorrhagic

manifestations• Excessive capillary

permeability• 100,000/mm3 platelets

Melioidosis

A: Cutaneous melioidosis B: lung abscesses on Chest X-RayC: corresponding CT Scan

D: Skin in a fatal disseminated melioidosis. E: splenic abscesses abdominal CT F: Aspirated pus- Prostatic abscessG: Abscesses on a CT scan.

Intracellular gram-neg Burkholderia pseudomallei, Saprophyte in Soil. Northern Australia -"hyperendemic" seasonal peaks in the wet seasons.Inhalation / inoculation / soil or water.

Leptospirosis spirochete:

• Severe jaundice, fever, hemorrhage with renal involvement - Weil’s disease.

• Leptospira icterohemorrhagica..• Zoonotic: Pri. hosts - mammals,

birds, reptiles, Contact with water, food, soil containing urine of infected animals.

• No spread from person to person.• NQ - Banana & dairy farmers.• Biphasic: Flu like first phase

followed in a week by Hemorrhage meninges, liver, renal failure - Weil’s disease.

Icterohemorhagic fever Jaundice + Hemorrhage

Q Fever• “Q - ? In an abattoir in Brisbane. • Coxiella burnetii, highly infectious• Cattle, sheep,goat and other live stock.• Biphasic:Acute & Chronic phase.• Acute: Fever, headache, fatigue, muscle & joint

pains, pneumonia.• Most recover - life long immunity but some

become chronic fatigue, hepatitis, endocarditis, pneumonia - serious.

• Meningitis/encephalitis: in both acute and chronic form in 1% patients.

• Vaccine – pre vaccine testing is important.

Chronic Fatigue Syndrome: (CFS)Infections in CFS:• Herpes, entero vir.• EBV, RRV• Q fever, Lyme &

mycoplasma.

Immunity in CFS.• Reduced

lymphocytes.• Decreased

immunoglobulins.• Altered immune

response to virus.

We can change our lives. We can do, have, and be exactly

what we wish.- - Anthony Robbins

CPC37: Week over view2013 Term 3

CPC 7Title: Multiple Co-morbidities

System: Musculoskeletal, Neurological , CVS, EndocrineAim: Educate students in clinical and pathological processes in

patients with bone abnormalities.Learning

Outcomes:Students will be

able to to

1. Demonstrate competency in History taking skills & focused clinical examination of patients who have sustained trauma

2. Describe the pathophysiology of fractures, osteoporosis, bone tumours (primary and secondary)

3. Describe the risk factors of osteoporosis.4. Describe the Healing in bone and other tissues following

trauma5. Describe the Basic sciences specific to tissue injury and

repair6. Outline the clinical approach to patient with multiple co-

morbidities and polypharmacy

Fracture Healing:

1 day

1-3 Wk (Soft)

6 Wk (Hard)

>8 Weeks

95

96

Paget’s Disease• Unknown etiology:• Excess osteolytic followed by

osteoblastic stage and finally exhaustion of cellular activity (osteosclerotic stage)

• Common (10%), Adult, One or all bones. Mild to severe types.

• Pain, sclerosis, deformity, fracture, nerve compression, deafness.

• Gross: thick, deformed, mosaic bone.

• Micro: mosaic lamellae, sclerosis, increased osteoclasts & blasts.

• Osteosarcoma - late age complication.

97

Vit-D deficiency:• Rickets (Children), Osteomalacia (adults).• Defective mineralization, more osteoid (protein).• Bowing of legs, Lumbar lordosis, rachitic rosary, Harrison

groove, Pigeon breast, Frontal bossing.

Benign - Malignant

Bone Disorders

99

Osteosarcoma:• 10-20y, (secondary in aged)• Knee* & shoulder* painful• Metaphysis of long bones. • Tumor of osteoblasts.• Rb gene mutations.• osteoid forming (fine lacy

microscopic osteoid) microscopic calcification, no lamellae.

• Normal: Checkerboard mix of type 1 & 2 fibers.“One Slow Fat Red Ox”

• Atrophy – neuronal, ischemic, inflammatory.• Myositis (inflam), Muscular Dystrophy (dis-org.)• Myopathy (non inflam) Toxic / Cong.• Tumours: Rhabdomyoma, Rhabdomyosarcoma.

Skeletal Muscle:

100

Normal Re-innervation group atrophy (nerve)

ATPase stain

Atrophic fibres

• Inherited, defective muscle structure. Dystrophin - Xp21.

• Hypertrophy / Atrophy, degeneration fat & fibrosis (pseudohypertrophy)

• Common X linked 2 types:– Duchenne MD – common, early 5y,

severe, death by 20y.– Becker MD -rare, late, less severe.

• Normal at birth, starts with pelvic & limb weakness heart failure.

Muscular Dystrophy:

Remember the Challenge….!Dec 2011:

4th Year Students at JCU School of Medicine set new record.…!!!100% Pass & Class Average over 70%

Yes We Can…!

Wish you all Success, Health,

& Happiness in life.

Need help for exams? You can still contact me..