The rest of medicine in six hours
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
mols
• 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
Protein Basics
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
1.0
1000
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
100%
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
NO M M transmission
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
Blood
R.B12
IF
R
R
IF.B12
B12 from food
Parietal cells
Bru
sh b
orde
r
IF.B12
IF
TC.B12
TC
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
SSSS
SS
SS
SSSS
‘A’ Chain ‘B’ Chain
‘C’ Peptide
Insulin
SSSS
SS
SS
SSSS
‘A’ Chain ‘B’ Chain
‘C’ Peptide
Insulin
SSSS
SS
SS
SSSS
‘A’ Chain ‘B’ Chain
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
A B
Glucose Transporters
GLUT 1 GLUT 3 GLUT 4
Not insulin dependent
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+
K+
Insulin Vesicle
Beta Cell
Sulphonylureas
SUR1SUR1
SUR1SUR1K+
K+
Sulphonylurea MoleculesInsulin Vesicle
Rising K+
SUR1SUR1
SUR1SUR1
Sulphonylurea MoleculesInsulin Vesicle
Depolarisation
SUR1SUR1
SUR1SUR1
Sulphonylurea Molecules
Ca++
Ca++
Ca++ Ca++
Ca++Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Insulin Vesicle
SUR1SUR1
SUR1SUR1
Sulphonylurea Molecules
Ca++
Ca++
Ca++ Ca++
Ca++
Ca++
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
Fig 1
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
2K+
2K+
H+
Na+
3Na+
3Na+
H+
Na+
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.
3 2 1
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
DD
II
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 &
Vein
Inguinal Ligament
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
Acid
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
HCO3
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
O One
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
Renin
• 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
Renin
• 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
RENIN
ACE
Angiotensinogen
Angiotensin I
Angiotensin II
Vasoconstriction•Direct•Via incr PNS NA
Salt retention•Aldosterone secrn
•Tubular Na+ reabsorption
Vascular growth•Hyperplasia•HypertrophyARB
ACE I
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
SkullDura mataPotential spaceArachnoid mataSubarachnoid spacePia mata
Cerebral Artery Middle Meningeal A.
Cerebral Vein
Subdural Haemorrhage
SkullDura mataPotential spaceArachnoid mataSubarachnoid spacePia mata
Middle Meningeal A.Cerebral Artery
Cerebral Vein
Subarachnoid Haemorrhage
SkullDura mataPotential spaceArachnoid mataSubarachnoid spacePia mata
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
loss
Coma, death if no intervention (or may resolve on their own)
Diagnosed by CT or MRI.
Sudden onset intense headache with stiff neck (as aneurysm bursts).
Possible papilloedema and retinal haemorrhage
Usually vomiting, possible loss of
consciousness for hours days
Diagnosed by CT or MRI.
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.