Path Flashcards
Where is cholesterol in the intetstine from?
- diet
- bile duct
How is cholesterol in the intestine solubilised?
in mixed micelles
Where are bile acids reabsorbed?
terminal ileum
What effect does cholesterol have on HMG-CoA-reductase?
it inhibits the enzyme
fates of cholesterol in the liver
- hydrolysed via 7-alpha-hydroxylase into Bile Acids, released via bile ducts (major determinants of cholesterol absorbtion)
- esterified via ACAT to cholesterol ester; incorporated with triglyceride and apoB into VLDLs with transfer protein MTP
How are triglycerides moved from small intestine to plasma?
via chylomicrons
How is LDL taken up by cells?
- binds to LDL R
- coated pits
- invagination
processed by lysosomes
How common is homozygous and heterozygous familial hypercholesterolaemia?
homozygous: 1 in 10^6
heterozygous: 1 in 500
What is PCSK9? What happens in gain and loss of function mutations?
a chaperone protein
its role is to bind to the LDL receptor and promote its degradation
gain of function mutations -> high LDL (because more LDL R is degraded and LDL not taken up by liver)
loss of function mutations -> low LDL
What medications are used to lower cholesterol? What effects do they have on HDL, LDL and TG?
statins - good reduction in LDL, slight reduction of TG, slight elevation of HDL
fibrates - very good at lowering TG, slight reduction/increase in LDL/HDL
resins - bind bile acids
Pharmacological approaches to obesity
orlistat - inhibits pancreatic lipase -> not hydrolysed, not absorbed, excreted via stool
surgical approaches to obesity (and indication)
bariatric surgery
if BMI >40
Different types of bariatric surgery
- gastric binding
- roux-en-Y bypass
- biliopancreatic diversion
Why can people with sarcioud have high Ca?
1-a-hydroxylase can be expressed lungs; uncontrolled; activation of vitamin D -> high CA
25-hydroxylase is found where?
Liver
Where is 1-alpha-hydroxylase found?
KIDNEYS
can be ectopiicallly expressed in sarcoid
When do you prescribe cholecalciferol and calcitriol?
calcitriol is dangerous because it is active Vit D3; only prescribed in renal failure; easy to overdose;
cholecalciferol - OTC, has to be activated;
Compare osteoporosis vs osteomalacia
Osteoporosis: reduced bone density with normal biochemistry
Osteomalacia: bone demineralisation; Blood: low Ca, low phos, high ALP/PTH?
How do you calculate corrected calcium?
CC = measured calcium + 0.02x(40-albumin)
T-score vs Z-score
T-score SD of 20yo
Z-score is SD from age-matched
Causes of osteoporosis
- childhood illness
- menopause
- corticosteroid therapy
- lifestyle: sedentary, EtOH, smoking, low BMI/nutritional
- endocrine: hyperprolactinaemia, thyrotoxicosis, Cushing’s
- other e.g. genetic, prolonged intercurrent illness
Mx of osteoporisis
lifestyle: weight bearing exercise, stop smoking, reduce etoh
Drugs
- vit D / Ca
- bisphosphonates (e.g. alendronate) -> decreased bone resorption -> very strong bone, not biodegradable; unnatural phosphate; osteoblasts Can use it, casts struggle with breakdown. do not have it with calcium, taken 1x/w on empty sttomach with water and nothing else. gut irritant.
alternative is 1/year IV zonlendronate
- teriparatide (PTH) derivative - anabolc;
- Strontium: anabolic + anti-respoptive
- oestrogens/HRT
- SERMs e.g, raloxifene (
Tamoxifen actions
Tamoxifen agonist in bone, antagonist in breast
raloxifene similar; good for bone and prevent Br ca but worsen Sx of menopause.
Which antibiotic groups belong to beta lactams?
Penicllins
Cephalosporins
Carbopenems
Monobactams
Examples og glycopeptide abx
teicoplanin
vancomycin
glycopeptides - what bacteria do they work against?
gram +ve only
Abx for C diff
Vancomycin (ora)
Can you give tetracycline to children and pregnant women?
No!
teratogenic and deposit in growing bones
Main risk of chloramphenicol
aplastic anaemia
Drug interaction of linezolid
interferes with SSRIs, can cause serotonin syndrome
Commonest cause of inborn errors of immunity
- antibody deficiency
Clinical features of immune deficiencies
- susceptibility to infection
- AID
- allergic diseases
- autoinflammatory disease
- viral related cancers (EBV, HPV)
What age group is mainly affected by PID?
children > adults
Examples of primary immune deficiencies
SCID
XLA
CGD
• Severe (sepsis, need for intravenous antibiotics or fungal drugs)
• Persistent ( Multiple course of antibiotics to treat standard bacterial chest or
sinus infection)
• Unusual infections (Opportunistic organism (Pneumocystis jirovecci, CMV, Live vaccine induced infection))
• Recurrent (More than 2 episodes of pneumonia within a year • More than 8 episodes of Otitis Media in a child)
Management of CGD
Cotrimoxazole and itraconazole prophylaxis
Adjunctive IFN-gamma, Stem cell and gene therapy
treatment of SCID
Stem cell transplant
?gene therapy (complicated by T-cell leukemia in 20%; T-cell function restored but not B-cells restored)
Life expectancy of patients with infection phenotype CVID
normal with IgG replacement therapy
causes of raised RBC count
Primary; polycythaemia vera
secondary: high altitude
Leukoerythroblastic anaemia - what is it? what does it indicate?
- variable degree of anaemia
- specific morphological features in the blood film (tear drop RBCs, nucleated RBCs, myelocytes)
indicates abnormal bone marrow infiltration (malignancy (leukaemia, lymphoma, myeloma; metastasis to bone; ), severe infection (rarely), myelofbrosis)
causes of reactive neutrophiilia
- PYOGENIC INFECTION
- corticosteroids
- underlying neoplasia
- tissue inflammation (e.g.colitis, pancreatitis myocarditis or MI)
causes for reactive eosinophlia
Parasitic infestation
Allergic diseases e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia.
Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)
Drugs (reaction erythema multiforme)
Causes for monocytosis
TB, brucella, typhoid
Viral; CMV, varicella zoster
sarcoidosis
chronic myelomonocytic leukaemia (MDS)
rare but seen in certain chronic infections and primary haematological disorders
causes for lymphocytosis
EBV, CMV, Toxoplasma (Infectious mononucleosis IM)
infectious hepatitis, rubella, herpes infections
autoimmune disorders
Sarcoidosis
causes for lymphopenia?
Infection HIV
Auto immune disorders
Inherited immune deficiency syndromes
Drugs (chemotherapy)
Triple assessment for Breast lump
Physical examination.
Imaging- Sonography, mammography & MRI
Pathology (cytopathology and/or histopathology).
Breast Cytopathology classification with definitions
C1 = inadequate
C2 = benign
C3 = atypia, probably benign
C4 = suspicious of malignancy
C5 = malignant
Breast history biopsy method
16-14 gauge needles (sometime 8-11 g)
US-guided or using stereographic techniques
with larger needles use vacuum assisted technologies, gives you more tissues.
Histology results in breast (classification and definition)
B1:normal tissue / inadequate sample
B2:benign lesion
B3:uncertain malignant potential
B4:suspicious of malignancy
B5:malignant
Duct ectasia
Inflammatory breast disease
5th -6th decade, multiparous women
Inflammation and dilation of large breast ducts.
Aetiology unclear.
Usually presents with nipple discharge.
Sometimes causes breast pain, breast mass and nipple retraction.
Cytology of nipple discharge shows proteinaceous material and inflammatory cells only.
Benign condition with no increased risk of malignancy.
Duct ectasia histology
Dilated duct
proteinaceous secretions
Periductal and interstitial inflammation – granulomatous
surround by inflammatory cells and macrophages
Acute mastitis
Acute inflammation in the breast.
Often seen in lactating women due to cracked skin and stasis of milk.
May also complicate duct ectasia.
Staphylococci the usual organism.
Presents with a painful red breast.
Drainage & antibiotics usually curative.
(Breast) fat necrosis
An inflammatory reaction to damaged adipose tissue.
Caused by trauma, surgery, radiotherapy.
Presents with a breast mass, late stages may show focal calcification.
Benign condition.
Galactocoele
Cystic dilation of a duct during lactation
Usually multiple ducts
Tender palpable nodules
Secondary infection may convert these to acute mastitis or abscess
Fibrocystic disease
A group of alterations in the breast which reflect normal, albeit exaggerated, responses to hormonal influences.
Very common.
Presents with breast lumpiness.
No increased risk for subsequent breast carcinoma.
Fibrocystic disease on histology
- fibrosis (replaces normal storma)
- cystic
- associated with adenoss/proliferaton of the gland
Three components, As the name indicates – Fibro – loose stroma is replaced by compressed fibrous tissue containing Cysts lined by flattened (larger cysts) to low cuboidal epithelium (smaller cysts) and adenosis – increased number of acini
Non proliferative changes – no usual type hyperplasia.
Fibroadenoma
A benign neoplasm composed of fibrous and glandular tissue.
Common.
Presents as a circumscribed mobile breast lump in young women aged 20-30.
Simple “shelling out” curative.
Phyllodes tumour
A group of potentially aggressive fibroepithelial neoplasms of the breast.
Uncommon tumours.
Present as enlarging masses in women aged over 50.
Some may arise within pre-existing fibroadenomas.
Vast majority behave in a benign fashion, but a small proportion can behave more aggressively.
Intraductal papilloma
A benign papillary tumour arising within the duct system of the breast.
Arise within small terminal ductules (peripheral papillomas) or larger lactiferous ducts (central papillomas).
Common.
Seen mostly in women aged 40-60.
Central papillomas present with nipple discharge.
Peripheral papillomas may remain clinically silent if small.
Excision of involved duct is curative.
Radial scar
A benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue.
Range in size from tiny microscopic lesions to large clinically apparent masses.
Lesions >1 cm are sometimes called “complex sclerosing lesions”.
Reasonably common lesions.
Thought to represent an exuberant reparative phenomenon in response to areas of tissue damage in the breast.
Usually present as stellate masses on screening mammograms which may closely a carcinoma.
Excision is curative.
Lifetime risk of breast cancer with BRCA mutation
up to 85%
components of breast histological grading
1) tubule formation
2) nuclear pleomorphism
3)mitotic activity.
each given 1-3 points -> added up
3-5 points = grade 1 (well differentiated).
6-7 points = grade 2 (moderately differentiated).
8-9 points = grade 3 (poorly differentiated).
Receptor status of low, high grade and basal like tumours of the breast
- Low grade tumours tend to be ER/PR positive and Her2 negative.
- High grade tumours tend to be ER/PR negative and Her2 positive.
- Basal-like carcinomas are often ER/PR/Her2 negative (“triple negative”).
Most important prognostic factor in breast tumours
The single most important prognostic factor is the status of the axillary lymph nodes.
Other important factors include tumour size, histological type, and histological grade.
Women age for NHS Breast screening and programme
Women aged 47-73 are invited for screening every three years / 50-70 at the moment
B5a vs B5b core biopsy result (breast)
B5a: DCIS
B5b: invasive carcinoma
Most common disease of the male breast
Gynaecomastia
Gynaecomastia
Refers to enlargement of the male breast.
Pubertal boys and older men aged over 50.
Idiopathic or associated with drugs (both therapeutic and recreational).
Histologically the breast ducts show epithelial hyperplasia with typical finger-like projections extending into the duct lumen. The periductal stromal is often cellular and oedematous.
Benign, no risk of malignancy.
RFs for atherosclerosis
Age
Sex
Genetics
Hyperlipidaemia
Hypertension
Smoking
Diabetes Mellitus
multiplicative risk factors
Characteristics of stable vs unstable plaque
Manifestations of IHD
Angina pectoris
Myocardial infarction
Chronic IHD with heart failure
Sudden cardiac death.
% stenosis for unstable angina
90%
Leading cause of sudden cardiac death
coronary artery disease
Virchow’s triad
blood
vessel wall
blood flow
low sodium high potassium diagnosis
addisons
Urgent treatment for phaeo
alpha blocker (e.g. phenoxybenzamine)
then you can add a beta blocker and arrange surgery
types of adrenal tumours causing high BP
pheochromocytoma (catecholamine secreting tumour)
conn’s syndrome (aldosterone secreting tumour)
Cushing’s syndrome (cortisol secreting tumour)
Surgery for adrenal tumours
remove the entire adrenal (more straightforward and less bleeding then when trying to resect a piece)
signs of hypovolaemia
tachycardia
reduced urine output
postural hypotension
dry mucous membranes
confusion / drowsiness
reduced skin turgor
!!!!!!!low urine sodium (<20)!!!!!! -> if you are deficient in sodium, you will not excrete that much.
treatment for hypovolaemic hyponatraemia
volume replacement with 0.9% saline
how do you treat a euvolaemic patient with hypo Na+?
fluid restriction
treat underlying cause
What is the % of hypertonic saline?
3% NaCl
when would you give 3% (hypertonic saline)
- reduced GCS
- seizures
- seek senior/expert help
How do you treat hyperNa+?
fluid replacement
treat the underlying cause
What is more common, HL or NHL?
Non-Hodgkin’s Lymphomas 80%
Hodgkin Lymphoma 20%
What lymphoma is associated with EBV?
Burkitts
histopathology starry sky appearance indicates
Burkitt’s lymmphoma
Chemotherapy regimen for Hodgkin’s lymphoma
ABVD
2-6 cycles
curative
Do you use radiotherapy in Hodgkin’s lymphoma?
often used alongside chemo in bulky areas or limited disease
however: very high risk of breast cancer in women
Causes for appropriate raised EPO
High altitude
Hypoxic lung disease
Cyanotic heart disease
High affinity haemoglobin
causes for inappropriate raised EPO
Renal disease (cysts, tumours inflammation)
uterine myoma
other tumours (liver, lung)
clinical presentation of essential thrombocytosis
Incidental finding on FBC (50% cases)
Thrombosis: arterial or venous
CVA, gangrene, TIA
DVT or PE
Bleeding: mucous membrane and cutaneous
Headaches, dizziness visual disturbances
Splenomegaly (modest)
Management of essential thrombocytosis
Aspirin: to prevent thrombosis
Hydroxycarbamide: antimetabolite. Suppression of other cells as well.
Anagrelide: specific inhibition of platelet formation, side effects include palpitations and flushing
aetiology of CNS tummours
- largely unknown
- previous head and neck radiation
- family history
What cancers most commonly give rise to brain mets?
breast
melanoma
renal
lung
prognosis of CNS mets
very poor
What is the most common brain tumour in children?
pilocytic astrocytoma
what does CNS tumour grade tell us?
survival
g1: benign, long term survival
g2: >5y
g3: <5y
g3: <1y
What is the most common CNS tumour in adults?
metastatic
normal ICP for supine adult
7-15 mmHg
epidemiology of stroke
3rd most common cause of death in the UK
leading cause of disability
what is the most common cause of non-traumatic intra parechnymal bleed?
hypertension
Main causes of subarachnoid haemorhages
- berry aneurysm
- htn
what % poeple have berry aneurysms?
1%
Risk factors for CNS infarctoin
cerebral ATHEROSCLEROSIS
smoking
diabetes
htn
haemorrhage behind ear sign name
battle sign
classic of a skull base fracture
chronic traumatic encephalopathy
patients presenting with psychiatric signs
environmentally triggered degenerative process
Define metaplasia
changing of one type of epithelium into another; it is reversible;
Barret’s oesophagus
- columnar lined eosophagus (rather than squamous)
- with goblet cells: intestinal metaplasia
- without goblet cells: gastric metaplasia
- reversible
What is the main cause of duodenal ulcers?
H. pylori
Whipple’s disease
caused by trypherma whippelii
can cause duodenal ?ulcers/?itis
Histological features of coeliac disease
villous atrophy
lymphocytes in tissue
what are opportunistic infections?
An infection caused by an organism that does not normally cause disease
serology
Measure levels of antibody in patients serum
CMV treatment (with SE)
Ganciclovir (IV): bone marrow suppression
Valganciclovir: oral
Foscarnet (IV) (nephrotoxicity)
Cidofovir (nephrotoxicity)
IVIg (with another drug for pneumonitis)
what are the different risks of CMV in patients posts SOT and HSCT
What are the main cells in the liver?
hepatocytes
bile ducts (epithelial cells)
blood vessels
endothelial cells
kupffer cells -> when activated become myofibriblasts
stellate cells (store vitamin a)
components of the hepatic triad
complications of liver cirrhosis s
portal htn
hepatic encephalopathy
cancer
What is spotty necrosis of the live indicative of?
acute hepatitis
(could be caused by viruses Orr drugs)
Potts fracture
ankle fracture
includes fibula and tibia
Band keratopathy
calcium in the eye
due to hypercalcaemia
if you see this it is unlikely to be cancer
osteitis fibrosis and cystic
can occur in long standing hyperparathyroidism
rare
loss of bone mass
RFs for calcium errand stones
FH
dehydration
hypercalciuria (>6mmol Ca/day)
hypercaalcaemia
HPTH
Ix for renal calcium stones
KUB
stone analysis
urine and serum biochemistry
Mx of renal calcium stones
lithotripsy
cystoscopy
lithotomy
drink lots and let the stones pass
How to manage primary hyperparathyroidism?
Acute: rehydration! fluids, fluids, fluids; 4L saline/day if they don’t have heart failure. If the calcium falls a tiny bit, you are winning.
Don’t give bisphosphonates.
avoid thiazides
Later: surgery
