The rest of medicine in six hours

transcript

Dr. Alan McLeod (F2)

The Plan

Day One

• A systematic approach• Chest Pain• Palpitations• Acute sob• Chronic sob• Haemoptysis• Painful Limb

Day Two

• TATT• Swallowing• Change in bowel habits• Hepatomegaly• Abdo pain • Pregnancy• Congenital abnormality• Head Injury• Emergency Management • Maximising your marks

I GET VINO…

I Infectious / inflammatory

G Genetic / Idiopathic

E Endocrine

T Trauma

V Vascular

I Iatrogenic / ingested

N Neoplastic

O Organs / Other

2 Minutes

10 Reasons to be Tired All The Time

TATT? Wine? For Me? Why Not?

I Infectious / inflammatory Multiple sclerosis, TB

G Genetic / ideopathic

E Endocrine Diabetes, Hypothyroid

T Trauma

V Vascular Anaemia

I Iatrogenic / ingested

N Neoplastic Lymphoma, leucaemia

O Organs / other Depression, obesity, lifestyle

Anaemia

Erythrocytes• Deformable

biconcave discs

Each carries• 250 MILLION Hb

• 1 billion O2 molecules

Anaemia – two classifications

Three basic causes

• Blood loss• Reduced erythrocyte

production• Increased erythrocyte

destruction

Three basic cell sizes

• Microcytic• Normocytic• Macrocytic

microcytic anaemia normocytic anaemia macrocytic anaemia

MCV < 76 femtolitres MCV = 76-95 fL MCV > 96 femtolitres

iron deficiency anaemia –commonest

lead poisoning

Sideroblastic anaemia Thalassaemia Anaemia of chronic disease Pyridoxine-responsive anaemia

anaemia of chronic disease – commonest Acute haemorrhage Haemolytic anaemia Bone marrow failure (aplastic anaemia)

Mixed iron and folate Pregnancy chronic renal failure riboflavin deficiency

With megaloblastic haemopoiesis on bone marrow examination

B12 deficiency

Folate deficiency

With normoblastic BM

Alcohol

Liver cirrhosis Hypothyroidism / myxoedema

Protein Basics

Primary Structure• Amino acid sequence

Secondary Structure• Folded primary

structure– Alpha helix– Beta pleated sheet

Tertiary Structure• Complex of

secondary structures

Quaternary structure• Associated tertiary

structures– e.g. Haemoglobin

MyoglobinHaemoglobin

pO2 (torr)

Tissues Lungs

Bohr effect and 2,3-BPG

Bohr effect: CO2 pH

Right ShiftEasier to release O2

pH (e.g. lactic acid)pCO2 (e.g. COPD)temp (e.g. exercise)2,3-BPG (e.g. altitude training)

Left ShiftReverse of these

10kPa0 pO2

Haemoglobin is Allosteric

T-Form• Bloomin’ – 2,3-BPG

can bind

• Tired – has no O2

R-Form

• Has enough O2 to Run

2,3-BPG

Thallasaemia

• One gene encodes the alpha globin

• Two genes encode the beta globin

• Beta thallasaemia minor = one gene faulty

• Beta thallasaemia major = both genes faulty

Comparison of Inheritance Modes

Autosomal Dominant

Autosomal Recessive

X-linked Dominant

X-linked Recessive

M = F M >> F (almost exclusively M)

2F : 1M M >> F (almost exclusively M)

Transmitted by both sexes

Trans by carrier females

Transmitted by both sexes

Trans by carrier females

M M transmission

occurs

NO M M transmission

Successive generation

affected

Phenotype may skip generations

Successive generation

affected

All daughters of affected M are

carriers

Iron Uptake & Storage

Iron is a vital element for life

• Humans have no active way of excreting iron

• 1-3 g stored

• 80% in haemoglobin

• 1 g lost / day from skin / mucosal shedding

• 1 g lost / day extra in menstruation

Absorbed

• Duodenum + upper jejunum

• Exact mech unknown

• About 10% of intake

• Lead toxicity reduces

• Vit C increases

Important Molecules

• Transferrin

• Small• Extracellular• Transporter• Holds 1 or 2 iron

• Ferritin

• Large • Intracellular• Storage molecule• Up to 45,000 iron

CKD and EPO

Erythropoietin• Glycoprotein• 10% from liver• 90% from kidneys

• Renal cortex• Peritubular capillary

endothelium– Responds to low O2

• Acts at bone marrow– Promotes erythrocyte

production– Promotes haemoglobin

synthesis

• Chronic Kidney Disease– Erythropoietin – Vitamin D – Renin

B12 and Folate

Involved in • RBC production

– Reduced RBC numbers

– Increased size– Reduceed O2 carrying

• DNA Sythesis• Tissue regeneration

Pernicious Anaemia• B12 deficiency• B12 absorbed via

intrinsic factor• IF produced by

Parietal cells in stomach

IF.B12

B12 from food

Parietal cells

IF.B12

TC.B12

TC B12Terminal Ileum

Tissue Cell

R: Non-specific B12 binding proteinIF: Intrinsic factorTC: Transcobalamin

Diabetes

• Pancreatic Islets• 60% beta cells

– Secrete insulin

• 25% alpha cells– Secrete glucagon

• Reciprocal action of hormones– Not usually present

together

• Secretions enter pancreatic vein into portal system

Diabetes

Type 1• Childhood• Failure insulin prod.• Insulin dependent

Type 2• Traditionally older• Insulin resistance• Lifestyle/drugs/insulin

Insulin

Peptide hormone• Alpha chain

– Species specific

• Beta chain– Biologic activity

• C-peptoid joins chains

Packaging and Release

Insulin production• Increased by glucose

– Transcription

– Translation

• Pre-proinsulin– Signal peptide cleaved

• Proinsulin– Disulphide links

– Excision of C-peptide

• Insulin

• Packaged in Golgi into secretory granules– Insulin– C-peptide

• Insulin forms hexamers

• Secreted via exocytosis

Describe the modifications that transform proinsulin into

insulin

‘A’ Chain ‘B’ Chain

‘C’ Peptide

Insulin

‘C’ Peptide

Insulin

Release of Insulin

• GLUT-2 admits glucose– Keeps intracellular conc

same as interstitial fluid

• ATP prod stimulated• ATP:ADP ratio changes• ATP binds to K+ channel• Channel closes• Cell depolarisation

• Depolarisation– Opening of voltage

gated Ca++ channels– Increased [Ca++]

• Exocytosis– Release of insulin

Insulin Stimulated Glucose Uptake

Glucose Transporters

GLUT 1 GLUT 3 GLUT 4

Not insulin dependent

Insulin Dependent

Low Affinity High Affinity Low Affinity

Basal glucose uptake for respiration

Energy supply to brain

Insulin related glucose storage

Foetal TissuesAdult RBCs

Low levels all tissues

Neurons Skeletal muscleCardiac MuscleAdipose Tissue

Functions of Insulin

Anabolic

• Promotes glucose uptake

• Promotes use of glucose as a fuel

• Promotes K+ uptake– Used to treat

hyperkalaemia

• Protein synthesis

• Blood proteins

• Muscle tissue

• TAG synthesis

• Glycogen synthesis

• Decreased proteolysis

• Decreased lipolysis

• Decr. gluconeogenesis

SUR1SUR1

SUR1SUR1K+

Insulin Vesicle

Beta Cell

Sulphonylureas

SUR1SUR1

SUR1SUR1K+

Sulphonylurea MoleculesInsulin Vesicle

Rising K+

SUR1SUR1

Sulphonylurea MoleculesInsulin Vesicle

Depolarisation

SUR1SUR1

Sulphonylurea Molecules

Ca++ Ca++

Ca++Ca++

Insulin Vesicle

SUR1SUR1

Sulphonylurea Molecules

Ca++ Ca++

Ca++Ca++

Insulin Vesicle

Insulin

Other Drugs

Metformin• Unknown mechanism• Gluconeogenesis• Insulin sensitivity• No weight gain• Epigastric discomfort• Diarrhoea• Anorexia

Glitazones• Alpha ketoglutarase

inhibitor• carbohydrate

breakdown in gut• Abdominal discomfort• Diarrhoea• Flatulence

2 Minutes

10 Causes of Abdo Pain

Phases of swallowing

Oral Pharyngeal Oesophageal

Bolus molding Glottis closesLarynx elevatesFood is deposited into the oesophagus

Peristaltic wave takes bolus downwardsGlottis opens

The nerves involved in swallowing are:• CN IX: Glossopharyngeal• CNX: Vagus• CNXII: Hypoglossal

Dysphagia: difficulty in swallowing

By location• Inside lumen

– Foreign body– Tumour

• Within wall: – Stricture – Achalasia

• Outside oesophagus– Lymphoma – Lung cancer

By Mechanism• Motor causes:

– Achalasia

• Mechanical causes:– Tumour– Stricture – Foreign body

• Neurological:– Bulbar palsy– Myasthenia gravis

Achalasia

• Damage to myenteric plexus

• Loss of peristalsis• Inability of lower

oesophageal sphincter to relax

• Barium swallow• Balloon dilatation

Myasthenia Gravis

• Acquired autoimmune– Thymic hyperplasia

75%– Thymoma 15%

• Non-thymoma– Two peaks– 10-30 yrs F>M– 60-70 yrs M>F

• Thymoma– 40-50 yrs

Features• Muscle weakness and

fatigueability, esp:– Periocular– Facial– Bulbar– Girdle

Normal Signal

Normal Response Response Blocked

Acetylcholine ACh receptor Anti AChR

Cholinergic Neurone

Myasthenia Gravis

Cholinergic Neurone

Defecation

• Mass movement into rectum

• If critical mass of stool in rectum distension of rectal walls:

• Defecation sensation• Defecation reflex• Contraction rectum• Relaxation int sphincter• Contr. Ext sphincter

If convenient• Increased pressure in

rectum relaxation of ext sphincter + expulsion of faeces.

If not convenient• Override by higher

centres no relaxation of external anal sphincter

• Prolonged distension reverse peristalsis

2 Minutes

5 Causes of Diarrhoea

5 Causes of Constipation

Diarrhoea? Waiter! More Wine…

I Infectious / inflammatoryGastroenteritis, food poisoningInflammatory bowels disease: Crohns, UC

G Genetic / Idiopathic

E Endocrine Hyperthyroid diseaseDiabetes mellitis: autonomic neuropathy

T Trauma

V Vascular / blood

I Iatrogenic / ingestedLaxatives: e.g. lactulose and magnesium sulphate

N NeoplasticColon cancerHormone producing including carcinoid, VIPomas and tubulovillous colonic adenoma

O Organs / otherPancreas: failure; Large bowel: constipation and overflow diarrhoea

Change in Bowel Habit

Diarrhoea• Passage of an excess

volume of stool• Usually increased

frequency and liquidity• May be:

– Abdo / rectal pain

– Urgency / incontinence

– Pus / blood

Treatment• Usually not antibiotics• Oral / IV rehydration• Opiates: codeine /

loperamide• Pancreatic enzymes if

deficient

Bowel Cancer

Symptom Right Left RectumWeight Loss + + / - -Anaemia + - -Rectal bleeding - + +Mass + - -Obstruction - + +Tympany - - +Virchows node + - -

Grading and Staging

Grading• Reflects histological

appearance• Grade 1 (low)• Grade 2 (medium)• Grade 3 (high)• As number goes up,

appearance is more abnormal

Staging• Reflects spread

around the body• Many systems –

different from cancer to cancer.

• Be aware of:– Dukes– TNM

Dukes’ Staging

TNM Staging

Complex but useful• T = Tumour

size/invasion• N = lymph nodes

affected• M = Metastases

http://www.sgpgi.ac.in/path/seminars/ccastage.html

Describe some of the features that make a disease suitable

for screening

A good screening Programme

• An important public health problem

• In which early detection is possible and advantageous

• With a reliable, acceptable test

• And available, effective treatment

• There should be agreement on who is suitable to investigate and treat.

Neoplasia

• 'Irreversible changes in genetic material of cells, due to exposure to certain noxious stimuli, leading to abnormal cellular growth patterns.’

• Tumours develop from a single cell – they are monoclonal

• Normal tissue is polyclonal

• Learn– Breast– Bowel– Lung

Neoplasia

• Oncogenes– Abnormal expression– Genes controlling cell

growth– Dominant

• Tumor suppressor genes– Loss of activity– Protect against

neoplasia– Recessive

Neoplasia

• Tumor suppressor genes– Loss of activity– Protect against

neoplasia– Recessive

• p53, Chromosome 17 – initiates DNA repair– prevents division of

cells with irreparable DNA damage

• Rb, Chromosome 13.– Abnormal copies of

this gene are implicated in retinoblastoma.

Growth Characteristics

Benign Malignant

Expands onlyGrows locally

Expands and invades local tissuesMay metastasise

Generally slower Generally faster

Cytoplasmic Characteristics

Benign Malignant

Normal or slight increase in nucleus:cytoplasm ratio

High nucleus:cytoplasm ratio

Resembles cell of origin (well differentiated)

Failure of differentiation

Retains specialisations Loses specialisationsDiploid Range of ploidy

Histological CharacteristicsBenign Malignant

Few Mitoses Many mitoses – some of which are abnormal

Cell uniform throughout tumour

Cells vary in shape and size (cellular pleomorphism) and/orNuclei vary in shape and size (nuclear pleomorphism)

Organised tissue Disorganised tissue

Invasion and Metastasis

• Invasion is the spread into adjacent tissues – may occur along natural tissue planes such as along nerves

• Metastasis is the spread of cells to distant parts of the body – there are several mechanisms for this

To Metastasise

• Changes occur in only some cells of the tumour

• By random mutation

• Binds to basement membr

• Becomes motile• Becomes able to attach

to extracellular matrix• Becomes able to degrade

extracellular matrix

• Must be able to survive and grow at site of implantation

Routes of

Metastasis

• Vascular

• Lymphatic

• Coelomic

Local and systemic effects

Local• Pressure• Invasion• Ulceration• Obstruction

Systemic• Weight loss

(cachexia)• Loss of appetite

(anorexia)• Fever• Anaemia• General Malaise

Who gets Cancers?

Inherited tendencies• Xeroderma

pigmentosum• Down’s syndrome• Ataxia telangectasia

Diseases predisposing to cancer

• FPC: Colon• HNPPC: Colon

Genes• Breast / ovarian

– BRCA1– BRCA2

• Colon– MLH1

• DNA mismatch repair• Dominant

– MSH2

What is a carcinogen? Suggest one together with its

mode of action.

Carcinogens

Cigarette smoke

Chemicals• PAH• Aromatic amines• Nitrosamines

UV Radiation

Ionising radiation• Radiotherapy• Radon gas (lung)• Industry/military

Carcinogens

Viruses• EBV (Epstein-Barr)• HPV (Papilloma virus)• HBV (Hepatitis B

virus)

Stages in carcinogenesis

• Initiation• Promotion• Progression

SPIKES – Bad News…

S SETTING UP: Having info ready; involving family as appropriate; location and privacy; time constraints, sit down; connect.

P Perception: What does the patient already know of believe?

I Invitation: find out what sort of invitation the patient is extending – do they want to know everything or do they wish to be told less

K Knowledge: as Invited in simple language

E Emotion and Empathy: Assessing the patients emotions and dealing with them empathically

S Summary and Strategy: Going back though it all again, identifying points that need futher expalnation and formulating a plan.

Inflammatory Bowel Disease

Ulcerative Colitis• Almost always rectal• Extends proximally• Unbroken lesion• Superficial mucosa

ulcers

Crohns Disease• Three Main Patterns:

– In any combination– Anorectal– Colitis– Terminal ileus

• Skip lesions• Full thickness ulcers

IBD Features

Common features• Diarrhoea ± blood /

pus / mucus• Abdo pain

Systemic • Fever• Malaise• Weight loss

Extra -intestinal• Pyoderma

gangrenosum• Erythema nodosum• Arthralgia• Arthritis• Iritis / uveitis• Apthous ulcers

IBD Features

Ulcerative Colitis• Presdisposes to PSC

and colon cancer 5%

Crohns Disease• RIF Mass, Anaemia,

Gallstones• Fissures• Abscesses

IBD Diagnosis

• Colonoscopy

• Biopsy

Ulcerative Colitis• ANCA (Anti-

Neutrophil Cytoplasmic Antibody)

Crohns Disease• ASCA (Anti-

IBD Management

Ulcerative Colitis• Surgery curative

(panproctocolectomy)• Antiinflammatory

5ASA (5-aminosalycilate)

• Corticosteroids• Immunosuppressants

Crohns Disease• Surgery not curative• Antiinflammatory

5ASA (5-aminosalycilate)

• Corticosteroids• Immunosuppressants• Antibiotics

Cholera and its toxin

• Vibrio cholerae

• Bacteria

• Gram –Ve straight or curved rod

• Water/food spread

• Toxin in two parts

• A: Active

• B: Binding

• Subunit B: 5 copies form a pentameric ring

• Binds intestinal cell

• Then A subunit detaches

• Subunit A: 1 copy

• Enters cell by receptor med endocytosis

Oral Rehydration fluid

Water + glucose + NaCl

Uses one of two SGLTs –

Downward Na+

gradient powers glucose transport

Water follows

Constipation? Waiter! More Wine…

I Infectious / inflammatory

G Genetic / Idiopathic Idiopathic slow passage

E Endocrine HypothyroidHypercalcaemia: parathyroid tumour

T Trauma Spinal injury

V Vascular / blood

I Iatrogenic / ingestedCodeine; morphine; iron; anticholinergics, antidepressants, some antacids

N NeoplasticColon / rectal cancerHypercalcaemia: bony mets / parathyroid

O Organs / otherImmobility, insufficient fluids, poor fibre intakeKidney failure

Change in Bowel Habit

Constipation• No formal definition

– Infrequent bowel opening

– Hard Stool– Difficulty passing stool– Pain passing stool

Treatments:• Optimise fluid and

fibre intake• Laxatives• Correct electrolyte

abnormalities• Surgery

Thyroid disease

HypO-thyroid

• Cold intolerance• Constipation• Exhaustion• Goitre• Psychosis• Hoarse voice• Course skin• Hyporeflexia• Hair loss

HypER-thyroid

• Heat intolerance• Diarrhoea• Agitation• Goitre• Psychosis• Lid retraction• Lid lag• Hyperreflexia• Clubbing

Hepatomegaly? A large one please

I Infectious / inflammatory Hepatitis, Abscess

G Genetic / Ideopathic Reidel’s lobe

E Endrocrine DM: fatty liver

T Trauma

V Vascular / blood Budd-Chiari syndrome

I Iatrogenic / ingested Alcohol / toxins: fatty liver

N Neoplastic

Primary liver carcinoma, Secondary metastasesChronic myeloid leukaemia, lymphoma

O Organs / otherBile ducts: obstruction; cholangitisHeart: right / congestive heart failure

The Liver

• Zone 1 is the periportal zone – this is the most oxygenated and most susceptible to damage from toxins

• Zone 2 is the mid zone• Zone 3 is the centrilobar

zone– this is the least oxygenated and most susceptible to ischaemic damage.

CentralVein

PortalTriad

The Liver - Functions

• Synthesis:– Albumin – without this

the oncotic pressure of blood would drop and oedema would result.

– Clotting factors – II, III, VII and IX

– C reactive proteins– Bile

• Conjugation– Steroids / drugs– Toxins / poisons

• Metabolism:– Carbohydrates– Fatty acids– Proteins

Hepatomegaly

Cirrhosis Cardiac failure Secondary metsEarlyGenerally regular surfaceNo jaundiceLateGenerally irregular surfaceWith jaundice

Generally regularNo jaundiceTense, tender liverPeripheral oedemaIncreased JVP

Generally irregularNo jaundice

Liver - Cirrhosis

• ‘An irreversable diffuse process characterised by destruction of hepatocytes, fibrosis, and nodular regeneration’

• Causes include: – Alcohol

– Hepatitis B & C viruses

– Gallstones

– PBC

– Chronic biliary obstruction

– Iron / copper overload(haemochromatosis / Wilson’s disease)

Liver - Cirrhosis

• ‘An irreversable diffuse process characterised by destruction of hepatocytes, fibrosis, and nodular regeneration’

• Consequences include:– Reduced hepatocyte

function– Portal hypertension– Increased risk ca.– Increased risk portal

vein thrombosis

Cirrhosis: Features

• Impaired metabolism of endogenous oestrogens– Testicular atrophy– Gynaecomastia– Spider naevi

• Low serum albumin– Ascites– Oedema

• Reduced synthesis clotting factors– Easy bruising

• Portal hypertension– Varices– Caput medusae– Splenomegaly

Cirrhosis: Ascites

• Three Mechanisms: • Increased hydrostatic pressure in portal veins– Increased transudation into

tissues

• Low oncotic pressure due to reduced albumin– Increased transudation into

tissues

• NA+ / H20 retention by kidney. Unknown mechanism.

Ascites: Other

• Transudate• Triffic• <25 g/L protein

– Cardiac failure– Hypoproteinaemia– Constrictive

pericarditis– Ovarian tumours, e.g.

Meig's syndrome.

• Exudate• Extremely nasty• >25 g/L protein

– Malignant disease– Pyogenic infection– Tuberculosis– Pancreatitis– Lymphoedema– Myxoedema

Portal Hypertension

A rise in pressure within the portal vein and its tributaries.Resultant from increased resistance to portal blood flow

caused by cirrhosis

Portosystemic Anastomoses: Between systemic and portal veins

Oesophageal vein and left gastric vein

Oesophageal varices*

Rectal/inferior rectal veins and superior rectal vein

Haemorroids

Small epigastric vein of anterior abdo wall and paraumbilical

Caput medusae

Alcohol dependency

Griffith Edwards and Gross (1976) defined some simple markers of alcoholism. The first four can be remembered by the mnemonic WANT:

W Withdrawal

A Activities – discarded in favour of alcohol

N Narrowing repertoir

T Tolerence

The others are lack of control and relapse

Alcohol dependency

The CAGE questionnaire

Alcohol dependence is likely if the patient gives 2 or more positive answers:

• Have you ever felt you should CUT down your drinking?• Have people ANNOYED you by criticising your drinking?• Have you ever felt bad or GUILTY about your drinking?• Have you ever had a drink first think in the morning to

steady your nerves or get rid of a hangover (EYE- opener)?

• Sensitivity of 93% • Specificity of 76%

2 Minutes

10 Causes of Abdo Pain

Abdo Pain? Waiter! More Wine…

I Infectious/inflammatory Appendicitis, gastroenteritis, food poisoning

G Genetic / Ideopathic

E Endrocrine Diabetic ketoacidosis (mainly in children)

T Trauma

V Vascular / blood

I Iatrogenic / ingested Surgical adhesions

N Neoplastic

O Organs / other LOTS and LOTs…

Abdominal Organs

Right Hypochondrial:LiverGall bladderColon (hepatic flexure)

Epigastric:StomachDuodenum r

Colon (transverse)Pancreas r

Aorta R

Left Hypochondrial:StomachSpleen Pancreas (tail) r

Colon (splenic flexure)

Right Lumbar:Colon (ascending) r

Kidney R

Umbilical:Small bowelColon (transverse)Aortic bifurcation R

Left Lumbar:Colon (descending) r

Kidney R

Right Iliac FossaCaecumAppendixOvary / ovarian tubeUreter

Suprapubic:Rectum Urinary bladder R

Left Iliac FossaColon (descending)Colon (sigmoid)Ovary / ovarian tubeUreter

Abdominal Organs

Embryology Arterial supply Visceral pain in

Red Foregut Coeliac trunk Epigastrium

Green Midgut superior mesenteric Umbilical quadr

Blue Hindgut Inferior Mesenteric Suprapubic quadr.

Junction Points:

Foregut becomes Midgut: Ampulla of Vater – halfway along second section of duodenum

Midgut becomes Hindgut: approximately at the splenic flexure

R= primary retroperitoneal structurer= secondary retroperitoneal structure

Right Iliac Fossa Pain

Gut Gynae Other Appendicitis Mesenteric

adenitis

Ectopic Pregnancy

Ovarian cyst torsion

Salpingitis Ureteric stone

McBurney’s Point

Umbilicus

Rt ASIS

Groin Hernia

Relative to inguinal lig• Under is Femoral• Over is inguinal

Relative to IEVs• Lateral is Indirect• Medial is Direct

Medial

Lateral

Inferior Epigastric

Vessels

Femoral Artery &

Inguinal Ligament

A hernia is: ‘a protrusion of any viscus from its proper cavity’

Anatomy and Complications

Inguinal Canal• Posterior Wall

– Transversalis fascia– Conjoint Tendon

• Anterior wall– External oblique

• Roof– Int Obl + Transv. Abdom.

• Floor– Inguinal ligament

Complications• Irreducibility• Obstruction• Strangulation

• Femoral more likely to have complications

GastrinSecretin

Fatty Acid Breakdown

Pepsinogen

GIP + CCK

: Induces release of…

: Inhibits release of…

GIP: Gastric inhibitory peptide

CCK: Cholecystokinin

Pepsinogen is the precursor of Pepsin – responsible for protein digestion

Digestive Secretions

Gastric (stomach) PancreaticCell Secretion Cell Secretion

Chief cell Pepsinogen

Acinar

Pancreatic amylase

Parietal cells HClPancreatic lipase

G cells GastrinRibonuclease

Deoxyribonuclease

Mucous cells Mucus Proteolytics:

Trypsin

Chymotrypsin

ElastaseEpithelial HCO3

Duct EpitheliaWater

Small Bowel

Function: Absorption of• Water• Electrolytes• Carbohydrates• Amino acids• Fats• Minerals (Ca, Fe)• Vitamins

Adaptations• Circ / long muscles• HUGE surface area• Vili• Epithelial cells with

microvilli• Single lacteal• Arteriole/venule –

venule drains via HPV

Large Bowel

Function 1: Storage

Function 2: Absorption• Water• Electrolytes

Function 3: Synthesis• Vit K, B12, thiamine,

riboflavin

Function 4: Breakdown• Bile acids• Bilirubin

• Adaptations• Bacterial colonisation

Comparison

Small Bowel• 4 M x 2.5 cm• Villi + Microvilli• Circular + longitudinal

muscle layers

Large Bowel• 1.2 M x 6-9 cm• Microvilli only• Circ muscl but with

long in three bands (taenia coli)

Pregnancy andCongenital Abnormalities

2 Minutes

10 Congenital Abnormalities

Ectopic Pregnancy

Menstrual Cycle

Menstruation

Follicular phase

• Reducing oestrogen and progesterone – reduction of neg feedback on pituitary

• Pituitary releases FSH/LH

Within the follicle

• LH + Thecal cells gives choleterol androgens

• FSH causes proliferation of granulosa cells

• FSH + Granulosa gives androgens oestrogens

Little Tiny Follicles Grow: LH + Thecal cells; FSH + Granulosa

Menstruation

• Follicular phase (cont…)

• Selection of dominant follicle – produces oestrogen

• Oestrogen levels rise until passing level for inducing positive feedback on LH

• FSH + oestrogen induce LH receptors

• LH receptor levels rise

• Luteinisation of follicle occurs– Progesterone produced

• Progesterone potentiates positive feedback of oestrogen

• LH Surge

Menstruation

Ovulation• Occurs 36 hours after

LH surge• Meiosis restarts within

the oocyte• Follicle wall breaks

down release of oocyte

Luteal phase• Corpus luteum

produces progesterone

• Induced by LH• Continued production

needed for pregnancy• LH levels falling…• What can save the

corpus luteum?!?

Basis of Pregnancy Test

• Implanting embryo produces human chorionic gonadotrophin (hCG)

• This stabilises the corpus luteum allowing continued progesterone production and pregnancy to continue

• hCG has 2 chains – alpha and beta

• Pregnancy test detects the beta-chain of the hCG molecule.

• Levels peak at 9-11 weeks

• Detectable 14 days post ovulation in urine and 6-7 days in plasma

Coarctation of the Aorta

• 2% Preductal (A)• 98% post ductal (B)

– Between aorta and DA

– ?infiltration ductus material

• Increased LV load– From extra resistance

• LV hypertrophy• Collateral arteries

Left Right Shunt

• Congenital / acquired defect in:– Interatrial septum– Interventricular septum

• PDA

• Blood follows path of least resistance LR

• Increased right output– Right heart failure– Pulmonary

hypertension• High blood flow

damage to pulmonary arteries

Transposition of Great Vessels

• Pulmonary artery and aorta arise from wrong sides

• Two systems in parallel not one in series

• Deoxygenated blood goes through systemic circulation

• Usually spotted on scan• Prostaglandins maintain a

PDA• Surgery to swap vessels

Tetralogy of Fallot

• Ventricular septal defect (Hollow arrow)

• Obstruction to right ventricular outflow (Solid arrow)

• Overriding aorta– Blood from both ventr.

• Right ventricular hypertrophy– High pressure load

For Next Year

• Renal bone disease• Acid/base balance• Counter currant

system• AKD• CKD• GN• Diuretics

The Corpuscle

• Produces protein-free filtrate of blood

• Ultrafiltration

• Three negatively charged layers– Capillary endothelium– Basement membrane– Capsule epithelium

• Poorly penetrate:– Molecules with a MW

of 70 kDa– Positively charged

The Corpuscle

EfferentAfferent Glomerulus

Glomerular (Bowman’s) Capsule

~ 13 mmHgNet Flow

25mmHg

Oncotic 25mmHg

Oncotic 50mmHg

Hydrostatic

50mmHgHydrostatic 12mmHg

Hydrostatic12mmHg

Hydrostatic

(Narrower)

The Nephron

• 1 – 1.5 MILLION nephrons per kidney

• 5-7 cm long

• Corpuscle + tubules + loop of Henle

• 2 types– 85% CORTICAL: Short loop reabsorption– 15% JUXTAMEDULLARY: long loop urine

concentration

A: Glomerulus

B: Afferent tubule

C: Efferent Tubule

D: Prox conv tubule

E:Loop of Henle: Thin Descending Limb

F:Loop of Henle: Thin ascenmding limb

G:Loop of Henle:Thick ascending limb

H: Distal conv tubule

I:Collecting ducts (drains ~6 tubules)

J:Duct of Bellini (drains 2 coll. Ducts)

The Ureter

• Four Layers• OutsideIn• Two smooth muscle

layers– Circular– Longitudinal

• Submucosa• Urothelium

The Ureter

• Four Layers• OutsideIn• Two smooth muscle

layers– Circular– Longitudinal

• Submucosa• Urothelium

C Clean

L Long

S Stream of

U Urine

I Inside

Ureteric Stones

Path of the Ureters• Passes from the

kidneys, inferiorly over the psoas (while moving laterally to medially), over the common iliac.

• Under the ovarian vessels, and down the pelvic sidewall to insert in the posterior surface of the bladder.

Constriction

Abdominal Ureter

Pelvic Ureter

IntramuralUreter

Renal Pelvis

• Secreted by juxtaglomerular apparatus

• Proteolytic enzyme• Cleaves the precursor

angiotensinogen into angiotensin I (decapeptide).

Stimulate renin release• Decreased [Na] in

distal tubule• Decreased renal

perfusion pressure• Reall sympathetic

nerve activity• Beta adrenergic

agonists

• PGI2

• Secreted by juxtaglomerular apparatus

• Proteolytic enzyme• Cleaves the precursor

angiotensinogen into angiotensin I (decapeptide).

Inhibit renin release• Angiotensin II• Atrial natriuretic

hormone

Angiotensin I

• A decapeptide• Not active

• Converted by ACE to the active octapeptide Angiotensin II

Angiotensin Converting Enzyme (ACE)– Membrane bound

enzyme– Mostly on epithelial

cells– Esp in lung– Also in heart, brain,

kidney, striated muscle

• Inactivates bradykinin

Angiotensin II

• Octapeptide• Active• Receptors include

AT1 (GPCR) and AT2• AT1 most important• AT2 effects subtle

and oppose AT1

Effects• Generalised

vasoconstriction• Increased NA from

sympathetic nerve• Increased Na+ reab-

sorption in prox tubule• Secretn of aldosterone• Cell growth in heart

and arteries

Angiotensinogen

Angiotensin I

Angiotensin II

Vasoconstriction•Direct•Via incr PNS NA

Salt retention•Aldosterone secrn

•Tubular Na+ reabsorption

Vascular growth•Hyperplasia•HypertrophyARB

Fluid Distribution

2/3rds rule• Approx 2/3 rds body is

water• Approx 2/3 rds is

extracellular

1,2,3,4,5 Rule• Extravascular fluid 12 L• Intravascular fluid 3 L• Tot (in 70 kg male): 45 L

Therefore• Extracellular: 12+3 = 15• Intracellular 45-15 = 30

Total 45 L

Intracellular: 30 L

Extracellular: 15 L

Extravascular: 12 L

Intravascular: 3 L

Head Trauma

SkullDura mataPotential spaceArachnoid mataSubarachnoid spacePia mata

Middle Meningeal A.Cerebral Artery

Cerebral Vein

Extradural Haemorrhage

Cerebral Artery Middle Meningeal A.

Cerebral Vein

Subdural Haemorrhage

Middle Meningeal A.Cerebral Artery

Cerebral Vein

Subarachnoid Haemorrhage

Cerebral Artery Middle Meningeal A.

Cerebral Vein

Extradural Subdural SubarachnoidBetween skull and dura

mataBetween dura mata and arachnoid mata

Into subarachnoid space

Middle meningeal a. Cerebral vein Cerebral artery

Major trauma Trivial trauma in elderly Berry aneurysm

Loss of consciousness for a short time

Lucid period lasting hours – days (as

pressure builds up within the skull)

Drowsiness, coma, death if no intervention

Diagnosed by CT or MRI.

Days – months pass (as pressure builds up slowly

within the skull)

Headache, drowsiness and confusionPossible hemiparesis / sensory

Coma, death if no intervention (or may resolve on their own)

Sudden onset intense headache with stiff neck (as aneurysm bursts).

Possible papilloedema and retinal haemorrhage

Usually vomiting, possible loss of

consciousness for hours days

Motor Neuron Features

Upper Motor Neuron• Paresis / Paralysis.• No muscle wasting• Clasp knife rigidity.• Hypertonicity• Hyperreflexia• Upgoing Babinski

reflex• Clonus.

Lower Motor Neuron• Paresis / Paralysis.• Muscle atrophy.• Fasciculation.• Hypotonicity

(flaccidity).• Hyporeflexia /

Areflexia.

Emergency ManagementD Danger? Check that the scene is safe

R Run Check for response

H Happily Call for HELP!

A Away andCheck and secure airway and C-spine

B Buy Check breathing, Resp rate

C Chocolate! Pulse, Heart rate

Emergency Management

D ‘Disability’Neuro exam: minimum is pupil size / response + GCS or AVPU

E ‘Exposure’1: Expose to seek injuries

2: Keep warm + take temperature

DEFG Don’t Ever Forget Glucose!!!

An AMPLE history

A Allergies

M Medications

P Past med Hx

L Last meal (time)

E Event – what happened

Fluid Distribution

2/3rds rule• Approx 2/3 rds body is

water• Approx 2/3 rds is

extracellular

1,2,3,4,5 Rule• Extravascular fluid 12 L• Intravascular fluid 3 L• Tot (in 70 kg male): 45 L

Therefore• Extracellular: 12+3 = 15• Intracellular 45-15 = 30

Total 45 L

Intracellular: 30 L

Extracellular: 15 L

Extravascular: 12 L

Intravascular: 3 L

So. HOW do I get the best marks?

1)Know EVERYTHING

2)Advance copy of exam

3)Strategy

Cannot be un-seen…The End.

The rest of medicine in six hours

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