Transition block Flashcards
Causes of pseudohyponatraemia include..
Hyperlipidaemia (increase in serum volume) or a taking blood from a drip arm
Hyponatraemia may be caused by..
Water excess or sodium depletion
Lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
Hyperpigmentation
Addison’s disease
Ix for addison’s disease
ACTH stimulation test (short Synacthen test)
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM
In addison’s disease, if an ACTH stimulation test is not readily available (e.g. in primary care) then..
9am serum cortisol
<100 nmol/l
Hyperkalaemia
Hyponatraemia
Hypoglycaemia
Metabolic acidosis
Addison’s disease
Mx of addisonian crises
Hydrocortisone or IV normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
Continue hydrocortisone 6 hourly until the patient is stable
Oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Mx of addison’s disease
Hydrocortisone - first half of the day
Fludrocortisone
Mx of intercurrent illness in addison’s disease
Glucocorticoid dose should be doubled, with the Fludrocortisone dose staying the same
ABG in Cushing’s disease
Hypokalaemic metabolic alkalosis
In cushing’s disease, ectopic ACTH secretion (e.g. secondary to ___________) is characteristically associated with very low potassium levels
Small cell lung cancer
Tests to confirm Cushing’s syndrome
Overnight (low-dose) dexamethasone suppression test
24 hr urinary free cortisol
Bedtime salivary cortisol
Cortisol not suppressed
ACTH suppressed
Cushing’s syndrome due to other causes (e.g. adrenal adenomas)
Cortisol suppressed
ACTH suppressed
Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)
Cortisol not suppressed
ACTH not suppressed
Ectopic ACTH syndrome
An _________ test is used to differentiate between true Cushing’s and pseudo-Cushing’s.
Insulin stress
__________ sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion
Petrosal sinus
Mx of Cushing’s disease
First-line = trans-sphenoidal removal of pituitary tumour (hypophysectomy)
Second-line = repeat trans-sphenoidal surgery, pituitary radiotherapy
Third-line = bilateral adrenalectomy
Source of prolactin
Anterior pituitary
Function of prolactin
Stimulates breast development (both initially and further hyperplasia during pregnancy)
Stimulates milk production
Prolactin secretion is under constant inhibition by…
Dopamine
What decreases prolactin secretion
Dopamine
Dopaminergic agonists
What increases prolactin secretion
Thyrotropin releasing hormone
Pregnancy
Oestrogen
Breastfeeding
Sleep
Stress
Drugs e.g. metoclopramide, antipsychotics
The syndrome of inappropriate ADH secretion (SIADH) is characterised by..
Hyponatraemia secondary to the dilutional effects of excessive water retention
SIADH involves an excessive release of..
ADH/ vasopressin
Cause of SIADH
Small cell lung cancer
Urine osmolality high (>100 mOsm/kg)
Urine sodium concentration high (>40 mmol/L)
SIADH
Mx of SIADH
Correction must be done slowly to avoid precipitating central pontine myelinolysis
Fluid restriction
Demeclocycline
Decreased secretion of ADH from the pituitary (_________ DI) or an insensitivity to ADH (_________ DI)
Decreased secretion of ADH from the pituitary (cranial DI) or an insensitivity to ADH (nephrogenic DI)
Causes of cranial DI
Idiopathic
Post head injury
Pituitary surgery
Craniopharyngiomas
Causes of nephrogenic DI
Genetic
Hypercalcaemia/hypokalaemia
Lithium
Sickle-cell
Polyuria + polydipsia
DI
High plasma osmolality, low urine osmolality
DI
+ water deprivation test
A urine osmolality of _____ mOsm/kg excludes diabetes insipidus
> 700
Mx of DI
Nephrogenic: thiazides, low salt/protein diet
Central: desmopressin
High T4, High T3, Low TSH and presence of TSH-R antibodies
Grave’s disease (hyperthyroidism)
Decrease in water permeability in late distal tubules and collecting duct
Nephrogenic Diabetes Insipidus
Does the following show hypo or hyperthyroidsm?
Hypothyroidism
Does the following show hyper or hypothyroidsm?
Hyperthyroidism
Carbonic anhydrase inhibitors, e.g. acetazolamide, exert their action predominantly in the…
Proximal convoluted tubule
Anti-diuretic hormone (ADH) acts on vasopressin 2 receptors in the __________ causing upregulation of aquaporin water channel 2 and increased water reabsorption
Collecting duct
What does the layers of the adrenal cortex produce?
GFR:
Zona Glomerulosa: mineralocorticoids like aldosterone
Zona Fasciculata: glucocorticoids like cortisol
Zona Reticularis: precursor androgens such as DHEA
The thyroid gland is responsible for producing which hormones?
Triiodothyronine (T3), thyroxine (T4) and calcitonin
Urine osmolality does not increase with fluid deprivation testing but upon administration of DDAVP urine osmolality increases
Central Diabetes Insipidus
Urine increases with fluid deprivation
Psychogenic polydipsia
Increased plasma fluid leading to decreased plasma osmolality and intracellular fluid shift
SIADH, overhydration
Plasma electrolyte loss leading to decreased plasma osmolality and intracellular fluid shift
Addison’s disease
Hypovolaemic hyponatraemia
Burns
Sweating
Diarrhoea
Vomiting
Fistulae
Addison’s disease
Euvolaemic hyponatraemia
Syndrome of inappropriate ADH release (SIADH)
Hypothyroidism
Hypervolaemic hyponatraemia
Renal/Heart/Liver failure
Nephrotic syndrome
What is the predominant stimulus for anti-diuretic hormone (ADH) release?
Increased plasma osmolarity
Low BP as well but that’s indirectly via ACE2
Unable to differentiate the sex of the baby at birth
21-hydroxylase deficiency - Congenital Adrenal Hyperplasia or CAH
Dilutional hyponatraemia
Low plasma osmolality
SIADH
Thyrotoxicosis can cause hypo/hypernatraemia
Hypernatraemia
Enzyme responsible for the catalysis of the conversion of T4 (thyroxine) into T3 (thyronine)
Iodothyronine 5’deiodinase - prevented by propylthiouracil
Where is ACTH secreted from?
Anterior pituitary gland
Target cell of ACTH
Cells in the zona fasciculata and zona reticularis
Most pituitary adenomas are non-functioning and therefore..
Will not cause hormone abnormalities
Oxytocin and vasopressin have the opposite effects on water homeostasis. How?
Vasopressin: promote water reabsorption in the collecting ducts of the kidney so expands plasma volume
Oxytocin: breast milk secretion and uterine contractions in pregnancy. Also works on the kidneys to stimulate excretion of water and sodium in urine
A glycoprotein hormone made up of an alpha and beta subunit
TSH
Can occur as a paraneoplastic syndrome in small-cell lung carcinoma
SIADH secretion
Hyponatraemia, low serum osmolality and a high or normal urine osmolality
SIADH secretion
Prolongation of PR interval and ST depression with T wave flattening/inversion
Hypokalaemia
Prolongation of PR interval, widening of QRS complex, tall T waves
Hyperkalaemia
Function of thyroid gland
Basal Metabolic Rate
Gluconeogenesis
Glycogenolysis
Protein synthesis
Lipogenesis
Thermogenesis
What needs to be increased for the thyroid gland to achieve its function?
Size and number of mitochondria within cells
Na-K pump activity
Presence of β-adrenergic receptors
Coupling of MIT and DIT gives _______ hormone and coupling of DIT and DIT gives _______
Coupling of MIT and DIT gives the triiodothyronine (T3) hormone and coupling of DIT and DIT gives the tetraiodothyronine (T4)
T3 and T4 are the active thyroid hormones. They are fat soluble and mostly carried by…
Plasma proteins – thyronine binding globulin (TBG) and albumin
Why is T4 used instead of T3 in the treatment of hypothyroidism?
Longer half-life
Plasma concentrations are easier to manage
The hypothalamus detects a low plasma concentration of thyroid hormone and releases thyrotropin-releasing hormone (TRH) into the..
Hypophyseal portal system
TRH binds to receptors found on thyrotrophic cells of the _________ gland, causing them to release thyroid stimulating hormone (TSH) into the systemic circulation.
Anterior pituitary
Actions of cortisol
Gluconeogenesis
Lipolysis
Immunosuppression
Anti-inflammation
Protein, fat, bone metabolism
Regulate calcium absorption from the GI tract
Regulate behaviour, mood, and cognition through activity on the CNS
Cortisol has a negative feedback effect by..
Inhibiting the production of CRH in the hypothalamus
Reducing the sensitivity of the anterior pituitary to CRH, which reduces ACTH release
Cushing’s disease is due to an excess of ______, Addison’s disease is due to a lack of ______, commonly due to autoimmune destruction of the ___________
Cushing’s disease is due to an excess of cortisol, Addison’s disease is due to a lack of cortisol, commonly due to autoimmune destruction of the adrenal cortex
Hormones in the anterior pituitary
Hormones in the posterior pituitary
What provides a rich supply to the pituitary endocrine cells?
Hypophyseal portal system
Hypothalamic-anterior pituitary-endocrine axis
Give an example of a primary endocrine disease
Addison’s disease - disease that affects hormone secretion in the organ that produces the hormone
Give an example of a secondary endocrine disease
Cushing’s disease - affects the endocrine organ that releases tropic hormones, which indirectly affects peripheral hormone secretion
Give an example of a tertiary endocrine disease
Tertiary adrenal insufficiency caused by a dysfunctional hypothalamus and decreased CRH production - disease of the hypothalamus
Four-Five key signs of inflammation
Calor or heat
Dolor or pain
Rubor or redness
Tumor or swelling
Functio laesa or temporary loss of function due to pain or swelling
Two main microbial factors that trigger inflammation are…
Virulence factors and pathogen associated molecular patterns (PAMPS)
________ are intracellular proteins that get released when a cell’s plasma membrane is injured or when a cell dies
DAMPs
PAMPs and DAMPs are recognized by ________
Pattern Recognition Receptors or PRRs
The inflammatory process usually begins with which cells?
Macrophages or mast cells
Function of inflammatory mediators released by mast cells?
Act on the endothelial cells surrounding the capillaries nearby, causing them to separate from each other
Cytokines causes capillaries to get larger, and increase vascular permeability, allowing plasma proteins and fluids to leave the circulation
Endothelial cells help spur the process of vascular permeability by releasing ________, which helps vasodilate the capillaries and make them more permeable
Nitric oxide
_________ get attracted to the site of infection by the chemokines and microbial products
Neutrophils
Then squeeze through gaps between 2 endothelial cells, until it reaches the other side - extravasation
_________ are the first leukocytes recruited during the acute inflammatory process
Neutrophils
Function of complement proteins in acute inflammation
Opsonisation
Direct bacterial killing via large pore-forming complexes
________ cells phagocytose pathogens and present bits of them to T lymphocytes
Dendritic
__________ are recruited to eat up dead and dying cells, so that the tissue can make room for new cells
Macrophages
The inflammatory response ends with..
Angiogenesis (temporary)
Triggered by growth factors released by macrophages
If there’s only mild damage, then the tissue regenerates back to its normal healthy state, but if there’s severe damage, then the damaged cells get replaced by…
Non-functional fibrous scar
What is primary intention?
When the wound edges come together - stem cells in the epidermis, or uppermost layer of skin are brought close together and can regenerate the damaged tissue near the surface of skin, leaving a minimal scar
What is secondary intention?
When the wound edges are too far from one another - tooth extraction sockets or severe burn injuries
What is tertiary intention?
Wound is cleaned and purposefully left open due to a high likelihood of being contaminated by bacteria - dog bite injury. Then closed by primary intention
What are the wound healing stages?
Hemostasis - blood clot
Inflammation
Epithelialisation/migration - basal cells, or the stem cells in the epidermis start to proliferate in order to replace the lost or damaged cells
Fibroplasia
Maturation - collagen cross linking/remodeling
Repigmentation
Factors that prevent proper healing and lead to chronic wounds
Decreased blood flow - diabetes, atherosclerosis, and prolonged compression
Infections
Uncontrolled swelling or edema around the wound
What is atrophy?
Reduction in size of cell/organ/tissue due to apoptosis (weight loss) or decreased cell number (polyubiquitination)
Give an example of a severe , pathological form of atrophy
Cachexia
Give an example of a physiological form of atrophy
Thymus involution
What is aplasia/hypoplasia?
Growth goes wrong in embryogenesis
Aplasia: Precursor cells absent so organ never forms (DiGeorge syndrome)
Hypoplasia: More common. Precursor cells present but not enough (Optic nerve hypoplasia)
Differentiate between hyperplasia and hypertrophy
Hyperplasia - cell increase in number
Hypertrophy - cell increase in size
Hyperplasia, bigger pack
Hypertrophy, tough lumberjack!
What type of pathological process is shown in hypertension?
Hypertrophy - heart has to pump blood against a high resistance and cardiac myocytes once again adapt by increasing the synthesis of myofilaments causing individual cells to get bigger
Give an example of a physiological hyperplasia
Organs with stem cells that can undergo cellular differentiation to become a mature cell in that organ
Compensatory hyperplasia occurs in organs that regenerate, like the..
Skin, lining of the intestines, the liver, and bone marrow
Hormonal hyperplasia occurs in organs that are regulated by hormones like organs in the..
Endocrine and reproductive system
Enlargement of the female breast during pregnancy
What pathological process is shown here?
Physiologic hyperplasia - prolactin, progesterone, and human placental lactogen stimulate the growth of glandular tissue in the breast causing them to enlarge
Overproduction of estrogen by an ovarian tumor, it can lead to excessive endometrial growth
What pathological process is shown here?
Endometrial hyperplasia
Hyperplasia can slip into…
Dysplasia
Abnormal growth/development of cells
Hyperplasia and hypertrophy usually occur together when there’s increased stress. An example of this is seen in..
In pregnancy, the uterus gets stimulated by estrogen, which lead to hypertrophy and hyperplasia of the smooth muscle cells in the uterine wall
Define metaplasia
Mature, differentiated cell type is replaced by another mature, differentiated cell type
What causes metaplasia?
Environmental stressor
Pathological process occurring in gastroesophageal reflux disease/Barrett’s esophagus
Metaplasia
Four major pathological microscopic changes
Cellular pleomorphism
Nuclear pleomorphism - hyperchromatism
Mitosis
Infection of the cervix of the HPV causes the cells to become..
Dysplastic
_________ is considered a precancerous state
Dysplasia
_________ is generally benign, while dysplasia is considered a precancerous state, that can develop into carcinoma
Metaplasia
__________ are actually mutated versions of proto-oncogenes, which are normal genes in charge of positive regulation of the cell-cycle
Oncogenes
Tumor suppressor genes are involved in…
DNA repair mechanisms and inhibiting transcription factors
What are the two phases of the cell cycle?
Interphase and mitosis
What does the interphase consist of?
G1 - cell grows and performs its cell functions
S - DNA is replicated
G2 - cell grows again before entering mitosis
G1 and G2, there are cell cycle control points called the..
G1 and G2 checkpoints, where the cell checks to see if there’s any DNA damage
The main control point is the ____ checkpoint
G1
If it turns out that there is DNA damage, then the cell can either _________ or _______
Enter a non-dividing state (G0) where the DNA repair mechanisms try to fix the problem
Apoptosis
Now, if the cell does get the go-ahead at the G1 checkpoint, it enters the ____ phase
S
If the cell gets past the G2 checkpoint, it enters ______
Mitosis - divides in two identical daughter cells
Cells tend to stay in that ___ phase, like neurons
G0
Give examples of proto-oncogenes that code for growth factors or growth factor receptors
RTK
Give examples of proto-oncogenes that code for signal transduction proteins
Ras
Give examples of proto-oncogenes that code for transcription factor that increases expression of cyclins and cyclin dependent kinases
Myc
Give examples of proto-oncogenes that code for transcription factor that code for proteins that inhibit apoptosis
Bcl-2
Give an example of a translocation mutation that causes oncogene to get overexpressed
B cell lymphoma called Burkitt lymphoma - myc (from chromsome 8 to 14)
Give examples of tumour suppressor genes
Rb and p53
Granulomas are associated with..
Exogenous foreign material
Columnar mucinous epithelium of the endocervix of postpubertal women is gradually replaced by squamous epithelium through a normal physiologic process known as..
Squamous metaplasia
What is the T zone?
Endocervical epithelium (columnar mucinous epithelium) is being actively replaced by squamous epithelium
Which genes increase the risk of breast and ovarian cancer?
BRCA1 & 2
Which genes increase the risk of colorectal and endometrial cancer?
Hereditary nonpolyposis colorectal cancer (Lynch II Syndrome)
RMI
Give examples of functional non-neolpastic cells
Follicular cysts
Corpus luteal cysts
Give examples of pathological non-neolpastic cells
Endometrioma
Polycystic ovaries
Theca lutein cyst - molar pregnancy
Give examples of epithelial benign neolpastic tumours
Serous cystadenoma
Mucinous cystadenoma
Brenner tumour - solid grey or yellow appearance
Give examples of benign germ cell tumours
Mature cystic teratoma (Dermoid cysts)
Give examples of sex-cord stromal tumours
Fibroma - present with Meig’s syndrome which is the association between these tumours and ascites/pleural effusion
______, _______ and _______ should be measured in all women under 40 due to the possibility of germ cell tumours
Lactate dehydrogenase, alphafetoprotein and hCG
In premenopausal women, rescan a cyst in 6 weeks. If it is persistent then monitor with..
Ultrasound, an CA125 3-6 monthly and calculate RMI
Low RMI (less than 25) moa
Follow up for 1 year with ultrasound and CA125 if less than 5cm
Moderate RMI (25-250) moa
Bilateral oophorectomy and if malignancy found then staging is required (with completion surgery of hysterectomy, omentectomy +/- lymphadenectomy)
High RMI (over 250) moa
Referral for staging laparotomy
_________ characterised by Psammoma bodies
Serous cystadenocarcinoma
___________ characterised by mucin vacuoles
Mucinous cystadenocarcinoma
Most common form of endometrial cancer is..
Adenocarcinoma - a neoplasia of epithelial tissue that has glandular origin and/or glandular characteristics
How does obesity predispose endometrial cancer?
Greater the amount of subcutaneous fat, the faster the rate of peripheral aromatisation of androgens to oestrogen
Genetic conditions that predispose to cancer, such as __________________, are a risk factor for developing endometrial cancer
Hereditary non-polyposis colorectal cancer (Lynch syndrome)
Leiomyomas are _____________ tumours of the uterus
Benign smooth muscle
Cervical polyps develop as a result of focal _________ of the columnar epithelium of the endocervix
Hyperplasia
Cervical polyps have a small risk of __________ transformation
Malignant
Cervical ectropion occurs when there is..
Eversion of the endocervix, exposing the columnar epithelium to the vaginal milieu
T or F: Cervical ectropion is an example of metaplasia
False
T or F: CIN is an example of metaplasia
True
The majority (70%) of cervical cancers are ___________. Of the remainder, 15% are ___________ and 15% are ___________ in type
The majority (70%) of cervical cancers are squamous cell carcinomas. Of the remainder, 15% are adenocarcinoma and 15% are mixed in type
Lichen sclerosus characteristically causes _______; producing a thin stratified squamous epithelium
Atrophy
Approximately 90% of vulval cancers are…
Squamous cell carcinomas
Squamous _____________ in the respiratory tract occurs in cigarette smokers where the respiratory pseudostratified columnar epithelium is replaced by stratified squamous epithelium
Metaplasia
Squamous _________ of the transformation zone of the uterine cervix is where a simple columnar epithelium is changed to be a stratified squamous epithelium
Metaplasia
Sequence of vaccular changes occurring during inflammation
Vasoconstriction - thromboxane A2 and reflex from pain receptors
Vasodilatation - histamine from mast cells and nitric oxide from endothelial cells
Increased permeability of vessels - oedema
Stasis of RBC - allows white blood cells to line up on the peripheral edge of the vessel
Epstein-Barr virus is an oncovirus for which cancers?
Burkitt’s lymphoma
Hodgkin’s lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
Human papillomavirus 16/18
Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer
Breast implants often become surrounded by a pseudocapsule and this may secondarily subjected to a process of…
Dystrophic calcification
___________ polymorphs are the cell type most commonly encountered in acute inflammation
Neutrophil
Which cells are involved in the haemostasis phase of wound healing?
Erythrocytes and platelets - seconds/minutes
Which cells are involved in the inflammation phase of wound healing?
Neutrophils, fibroblasts and macrophages - days
Which cells are involved in the regeneration phase of wound healing?
Fibroblasts, endothelial cells, macrophages - weeks
Which cells are involved in the remodelling phase of wound healing?
Myofibroblasts - 6 weeks to 1 year
What is anaplasia?
Loss of structural differentiation and is seen in malignant change
What is dysplasia?
Loss of maturity of epithelium type, and is the result of incomplete cellular differentiation
What is metaplasia?
Change from one cell type to another cell type
Potent mediators of vascular dilatation include..
Histamine, prostaglandins, nitric oxide, platelet activating factor, complement C5a (and C3a) and lysosomal compounds
Vasoconstrictors in acute inflammation..
Serotonin
Neutrophil polymorphs = Acute inflammation
__________ = Chronic inflammation
Granuloma
Leucocyte extravasation consists of..
Chemoattraction, rolling, tight adhesion and transmigration
Which cells are responsible for chemoattraction in leucocyte extravasation?
Macrophages in the affected tissue release cytokines such as IL-1, TNF-α
Which cells are responsible for tight adhesion in leucocyte extravasation?
Leucocytes express integrins in response to the cytokines. These bind to ICAM proteins on endothelial cells
Which cells are responsible for transmigration in leucocyte extravasation?
PECAM proteins on both endothelial cells and leucocytes
Cellular changes that occur after vascular changes
Leukocyte extravasation (leakage of fluid)
Margination, rolling and adhesion of neutrophils due to selectins and adhesion proteins
Transmigration across the endothelium into the tissues
Migration towards chemotactic stimulus (bacterial products or endogenous chemoattractants)
After cellular changes, leukocyte activation occurs, which is induced by..
Microbes, products of necrotic cells, antigen-antibody complexes
Production of prostaglandins
Degranulation and secretion of lysosomal enzymes
Cytokine secretion
Modulation of leukocyte adhesion molecules
_______ causes secretion of water and electrolytes
Secretin
_________ comprise 50% of the cells of the anterior pituitary gland
Somatotrophs
Mechanism of the body’s response to a decrease in blood pressure?
Antidiuretic hormone promotes water reabsorption by the insertion of aquaporin-2 channels
Folate/Vit B12 absorption is dependent on pancreas
Vit B12
Give examples of surface epithelial cell tumours
Serous/mucinous
Endometriod
Cystadenocarcinoma
Give examples of germ tumours
Teratoma
Dysgerminoma
Give examples of sex cord stromal cells
Fibroma
Granulosa theca cell tumour
Sertoli Leydig cell
Metastasis to ovaries usually occur from..
Breast
Lung
Colon
What is the action of LH in males?
Stimulates the Leydig cells in the testes to produce testosterone
What is the action of FSH in males?
Sperm production in the Sertoli cells of the testes (spermatogenesis)
Synthesis of proteins important for the production and action of steroid hormones
What is the function of LH and FSHin females?
Stimulate the ovary to produce mature gametes, as well as synthesise and secrete oestrogens and progestins
LH binds to ______ and ______ cells on developing follicles
After ovulation, LH binds to cells of the ______. It acts on theca cells to produce progestins and androgens.
Androgens enter granulosa cells and are then converted to ______
LH binds to theca and granulosa cells on developing follicles
After ovulation, LH binds to cells of the corpus luteum. It acts on theca cells to produce progestins and androgens.
Androgens enter granulosa cells and are then converted to oestrogens
GnRH is released in a ________ fashion from neurons in the hypothalamus
Pulsatile
In prostate cancer, _________ are administered to suppress LH and FSH release, thereby reducing testosterone production
Long-acting GnRH analogue
What are the direct effects of GH?
Increased lipolysis
Glycogenolysis
Stimulation of stem cell division and differentiation of daughter cells in epithelia and connective tissues
What are the indirect effects of GH?
via IGF-1:
Increased protein synthesis and cell growth
Increased carbohydrate oxidation
Whilst GHRH promotes GH release, the hypothalamus also produces ____________ which inhibits GH
Growth hormone inhibiting hormone (somatostatin)
Growth hormone axis
Depression
Reduced muscle mass and strength
Reduced bone mass
Reduced energy
Possible cardiac dysfunction
Growth Hormone Deficiency
Large extremities with growth of hands, feet and jaw
Paraesthesia in the extremities
Amenorrhoea
Coarse facial features, wide nose and rounded face
Hypertension
Cardiomegaly (enlarged heart)
Growth Hormone Excess - acromegaly
Several factors including stress, exercise, nutrition, hormones such as _________ (synthesised by the stomach) and sleep modulate the production of growth hormone
Ghrelin
Within the hypothalamus, neurons from the ________ and _________ nuclei extend into the posterior pituitary
Paraventricular and supraoptic
Activation of oxytocin receptor (GPCR) results in a significant influx of _________ ions into the cell
Calcium
___________ release further oxytocin, forming a positive feedback loop
Contractions
Oxytocin reaches the _________ cells lining the alveoli in the breast, causing these cells to contract
Myoepithelial
Which hormone is responsible for milk ejection reflex or milk let-down reflex?
Oxytocin
__________ released during ejaculation stimulates contraction of the vas deferens and prostate gland for the emission of sperm and prostatic secretions
Oxytocin
_____ increases the number of oxytocin receptors present in the myometrium and decidua during this time.
Oestrogen
SIADH can come from..
Small cell lung carcinoma
Mutations in vasopressin gene
Cranial diabetes insipidus
Mutations in ADH receptor gene or aquaporin-2 gene
Nephrogenic diabetes insipidus
Most common cause of neck swellings
Reactive lymphadenopathy
Rubbery, painless lymphadenopathy
Pain whilst drinking alcohol is very uncommon
There may be associated night sweats and splenomegaly
Lymphoma
Hypo-, eu- or hyperthyroid symptomatically
Moves upwards on swallowing
Thyroid swelling
< 20 years old
Usually midline, between the isthmus of the thyroid and the hyoid bone
Moves upwards with protrusion of the tongue
May be painful if infected
Thyroglossal cyst
Older men
Posteromedial herniation between thyropharyngeus and cricopharyngeus muscles
Usually not seen but if large then a midline lump in the neck that gurgles on palpation
Dysphagia, regurgitation, aspiration and chronic cough
Pharyngeal pouch
A congenital lymphatic lesion (lymphangioma) typically found in the neck, classically on the left side
Most are evident at birth (<2 years)
Cystic hygroma
An oval, mobile cystic mass that develops between the sternocleidomastoid muscle and the pharynx
Failure of obliteration of the second branchial cleft in embryonic development
Early adulthood
Branchial cyst
More common in adult females
Around 10% develop thoracic outlet syndrome
Cervical rib
Pulsatile lateral neck mass which doesn’t move on swallowing
Carotid aneurysm
Metabolic _______ is associated with hyperkalaemia
Acidosis
Causes of Hyperkalaemia
ACE inhibitors
Addison’s disease
Acute kidney injury - haemodialysis
Causes of Hypokalaemia
Bendroflumethiazide
Furosemide
Primary hyperaldosteronism
Pyloric stenosis
Cushing’s disease
Hypokalaemic periodic paralysis
Hypertension
Hypokalaemia
Metabolic alkalosis
Primary hyperaldosteronism
Ix for Primary hyperaldosteronism/conn’s syndrome
Plasma aldosterone/renin ratio
High-resolution CT abdomen
Adrenal vein sampling to differentiate whether if it’s unilateral or bilateral
Mx of Primary hyperaldosteronism/conn’s syndrome
Adrenal adenoma: surgery (laparoscopic adrenalectomy)
Bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
Causes of hyponatraemia
Thiazides
Loop
SSRI
Lung cancer
Addison’s
Carbamazepine
Sulfonylureas
Acute intermittent porphyria
Cause of hypernatraemia
Hyperosmolar hyperglycaemic state
Diabetes insipidus
Hypovolaemia
Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
Raised serum osmolarity (> 320 mosmol/kg)
Hyperosmolar hyperglycaemic state
Mx of HHS
IV 0.9% sodium chloride solution - 0.5 - 1 L/hour
Insulin if blood glucose stops falling while giving fluids
Venous thromboembolism prophylaxis
Mode of inheritance in FH
Autosomal dominant - high levels of LDL-cholesterol
We should suspect FH as a possible diagnosis in adults with..
A total cholesterol level greater than 7.5 mmol/l and/or
A personal or family history of premature coronary heart disease (an event before 60 years in an index individual or first-degree relative)
If one parent is affected by familial hypercholesterolaemia, arrange testing in children by..
Age 10
If both parents are affected by familial hypercholesterolaemia, arrange testing in children by..
Age 5
Mx of FH
Referral to a specialist lipid clinic
High-dose statins (discontinued in women 3 months before conception)
What type of inheritance is shown here?
Mitochondrial
Affected females transmit the disease to all their children
Affected males don’t
Which genetic condition is detected via deletion using fluorescence in-situ hybridisation?
Cri du chat syndrome
Which genetic condition is detected via duplication using fluorescence in-situ hybridisation?
Chacot marie tooth disease
Which genetic condition is detected via translocation using fluorescence in-situ hybridisation?
Philadelphia chromosome - CML
Karyotype 47XY + 21
Down Syndrome
Robertsonian Translocation
22.q11.2 Deletion
DiGeorge Syndrome
47, XXY
Klinefelter syndrome
45, X
Turner syndrome
Turner Syndrome is diagnosed by…
Karyotyping
Mode of inheritance seen in turner’s syndrome
Sporadic - monosomy of the X chromosome
46 XY/46 XX
Noonan’s syndrome
Androgen sensitivity syndrome mode of inheritance
X-linked recessive
Mode of inheritance seen in Klinefelter
Sporadic - non-disjunction during meiosis
X inactivation - Barr body
Mode of inheritance seen in Fragile X syndrome
X-linked inheritance - CGG trinucleotide repeat
Robertsonian/Reciprocal translocation is seen in down syndrome
Robertsonian
___________ non-disjunction is the most common mechanism underpinning the development of Down syndrome
Chromosomal
Trisomy 18
Edward’s
Trisomy 13
Patau
If a mutation develops in the mismatch repair genes, the cell can no longer correct (insertions/deletions) errors, increasing the overall mutation rate in the cell. This is termed…
Microsatellite instability.
An example of a condition with a mutated mismatch repair gene is..
Hereditary non-polyposis colorectal cancer (HNPCC)
Antithrombin III deficiency mode of inheritance
Autosomal dominant
Hypotonia, small hands and feet and undescended testes
Prader–Willi syndrome
Expansion of cytosine–guanine–adenine (CAG) repeats
Huntington’s disease
Microcephaly with a prominent occiput, low-set ears and an abnormally small jaw. She also has clenched fists with overlapping fingers on both hands
Edwards syndrome - Trisomy 18
Amniocentesis: _____ weeks
CVS: _____ weeks
Amniocentesis: 16-20 weeks
CVS: 11-14 weeks
With autosomal-dominant conditions, for the child to develop the disease, the mother or father must be _________ of the dominant allele
Carriers
True hyponatraemia with a markedly low urine osmolality (< 100 mOsmo/kg) narrows the differential diagnosis to either ___________________ or _______________
Psychogenic polydipsia
Low solute intake (solely beer or tea and toast diet)
_______ can decrease the absorption of tetracycline antibiotics (e.g. doxycycline)
Oral iron (e.g. ferrous sulfate)
Give iron at least 3 hours before or 3 hours after tetracycline
_____________ can prolong bleeding times and cause gastrointestinal toxicity. These effects are aggravated when given with anticoagulants (e.g. warfarin)
Naproxen, and other NSAIDs
Alter warfarin dose to ensure ref range
Monitor INR + bleeding signs
Drug metabolism commonly occurs in the liver through__________ or ___________
Phase I reactions (oxidation, reduction, or hydrolysis)
Or
Phase II reactions (e.g. glucuronidation)
Most drug metabolism is carried out by phase I reactions involving…
Isoenzyme cytochrome P450 (CYP450)
T or F:
Enzyme induction: takes approximately two-three weeks to develop and wear off
Enzyme inhibition: takes only days to develop
True
Enzyme inducers
GP RAPS:
Griseofulvin
Phenytoin
Rifampicin
Alcohol (chronic)
Phenobarbital
Sulfonylureas (e.g. gliclazide)
Phenytoin is a potent CYP3A4 inducer which induces the metabolism of ____________ contraceptives (e.g. ________), allowing ovulation to occur
Progesterone-only contraceptives (e.g. desogestrel)
IUD, depots, barrier for less than two months use of phenytoin
Consider additional consistent use of condoms during and for at least 28 days after stopping phenytoin
Enzyme inhibitors
COKE, Alcohol and Grapfruit juice with your PIs
Cimetidine
Omeprazole
Ketoconazole
Erythromycin
Portease inhibitors
Sodium Valproate
Clarithromycin inhibits the CYP3A4 enzyme responsible for metabolising ____________, subsequently increasing the plasma concentration
Simvastatin
Withhold simvastatin while administering clarithromycin
Methotrexate is a substrate for OAT1 and/or OAT3 so can compete with __________ which are involved in the active renal secretion of drug
NSAIDs
Avoid NSAIDs with methotrexate and use alternative analgesia
Example of a beneficial additive/synergistic interaction
Ramipril inhibits the ACE enzyme from converting angiotensin I to angiotensin II, causing increased vasodilation due to inhibition of bradykinin breakdown
Amlodipine causes the direct relaxation of the vascular smooth muscles
No action is required unless hypotension occurs
Example of a harmful additive/synergistic interaction
Enoxaparin with apixaban
Additive anti-Xa activity. This increases the risk of bleeding
Example of an antagonism interaction
Propranolol (blocks b2 which can make asthma worse) with salbutamol
Cardioselective Beta Blockers Are MEAN
Celiprolol
Bisoprolol
Betaxolol
Acebutolol
Metoprolol
Esmolol
Atenolol
Nebivolol
Omeprazole with clopidogrel interaction
Omeprazole can decrease the antiplatelet effects of clopidogrel (give cimetidine instead)
SSRIs with NSAIDs interaction
Can increase GI bleading
Methotrexate with trimethoprim interaction
Risk of severe bone marrow suppression & subsequent pancytopenia (monitor FBC and give folinic acid as an antidote)
Verapamil with beta-blockers interaction
Additive cardiac depression effects (leading to bradycardia, asystole, sinus arrest) so never give verapamil in IV
ACE inhibitors with potassium-sparing diuretics (e.g. spironolactone/eplerenone) interaction
Increases the risk of hyperkalaemia and acute kidney injury
Which drug causes unexplained rhabdomyolysis?
Statins
Absorption of levothyroxine is reduced by…
Food and caffeine
Antacids
Calcium and iron supplements
Long-term side effects of taking omeprazole
Osteoporosis, Clostridium difficile infection, hypomagnesaemia and vitamin B12 deficiency
Omeprazole drug interactions
SSRI
Clopidogrel
Methotrexate
Key counselling point of taking amlodipine?
Dizzy so blood pressure monitoring will be required during treatment
Amlodipine drug interactions
Simvastatin - rhabdomyolysis
Diltiazem and verapamil - arrythmias
Ramipril - hypotension
Joint pain (arthralgia), muscle discomfort (myalgia), nausea & vomiting, flatulence, constipation and gastrointestinal discomfort
Atorvastatin
Excess dosing causes symptoms of hyperthyroidism
Levothyroxine
Dizziness, flushing, palpitations, headaches, peripheral oedema (usually leg swelling) and headaches
Amlodipine
Dry cough
Hyperkalaemia
Angioedema
Ramipril
Rampiril drug interactions
NSAIDs - hyperkalaemia
Lithium
Bisoprolol interactions
Verapamil, diltiazem and amiodarone - heart block
Gastrointestinal and taste disturbances
Weight loss
Metformin
Don’t mix _____ or _____ with ciprofloxacin or doxycyclin
Calcium or ferrous sulphate
Causes of decreased compliance
Pulmonary oedema
Pulmonary fibrosis
Pneumonectomy
Kyphosis
Causes of resp alkalosis
Anxiety leading to hyperventilation
PE
Salicylate poisoning
CNS disorders: stroke, subarachnoid haemorrhage, encephalitis
Altitude
Pregnancy
ABG in overdose
Mixed respiratory alkalosis and metabolic acidosis
Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis
What would be the expected ABG of a normal pregnant woman?
Compensated respiratory alkalosis
ABG seen in Hyperemesis gravidarum
Metabolic alkalosis
What is anticipation?
Increased severity or earlier onset of disease in succeeding generations
What is mosaicism?
Genetically distinct cell lines in the same individual
What is codominance?
Both alleles contribute to the phenotype of a heterozygote - ABO blood groups
Heteroplasmy vs Homoplasmy
Pesence of more than one type of organellar genome (mitochondrial DNA or plasmid DNA) within a cell or individual and explains why there is a varying expression of disease in this patient’s family
Homoplasmy is the opposite to heteroplasmy
What is Penetrance?
Proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype
What is Expressivity?
Degree of variation in expression of a non-binary phenotype
Example of trinucleotide repeat disorders
Fragile X (CGG)
Huntington’s (CAG)
Myotonic dystrophy (CTG)
Friedreich’s ataxia (GAA)
Spinocerebellar ataxia
Spinobulbar muscular atrophy
Dentatorubral pallidoluysian atrophy
What is Aneuploidy?
Presence of an abnormal number of chromosomes in the cell, for example, an extra chromosome in Down syndrome
Which genetic test is used to selectively amplify and detect short genomic sequences?
PCR
Denaturation, annealing and elongation
Which genetic test is used to measure proteins?
ELISA
Which test is used to detect genomic sequence on a chromosome?
Fluorescence in situ hybridisation - labelled probe
Which genetic technique is used to measure gene expression levels by hybridising them with a sample containing DNA or RNA?
Microarray
___________ is used in rheumatoid arthritis and Crohn’s
Infliximab (anti-TNF)
__________ is used in non-Hodgkin’s lymphoma and rheumatoid arthritis
Rituximab (anti-CD20)
__________ is used in metastatic colorectal cancer and head and neck cancer
Cetuximab (epidermal growth factor receptor antagonist)
_____________ is used in metastatic breast cancer
Trastuzumab (HER2/neu receptor antagonist)
_______________ is used in chronic lymphocytic leukaemia
Alemtuzumab (anti-CD52)
________ is used in prevention of ischaemic events in patients undergoing percutaneous coronary interventions
Abciximab (glycoprotein IIb/IIIa receptor antagonist)
___________ is used to prevent organ rejection
OKT3 (anti-CD3)
What is the function of Azathioprine?
Immunosuppressant that inhibits purine synthesis
__________ test can be used to assess azathioprine toxicity
A thiopurine methyltransferase (TPMT)
Azathioprine can cause a significant interaction with…
Allopurinol
What is the function of Ciclosporin?
Immunosuppressant widely used to prevent transplant rejection
Explain the pharmacology of Ciclosporin
Decreases clonal proliferation of T cells by reducing IL-2 release. It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphatase that activates various transcription factors in T cells
Anti-CCP
RA
Anti-mitochondrial
Primary biliary cholangitis
ANA antibodies
Systemic lupus erythematosus
Sjogren’s syndrome
Anti-RNP antibody
Mixed connective tissue disease
Anti-thyroid peroxidase antibody
Hashimoto’s disease
Anti-tissue transglutaminase antibody
Coeliac
Rheumatoid factor
Rheumatoid arthritis
Sjogren’s syndrome
Smooth muscle autoantibodies
Autoimmune hepatitis
TSH receptor antibody
Grave’s
cANCA
Granulomatosis with polyangiitis/ Wegener’s granulomatosis
pANCA
Eosinophilic granulomatosis with polyangiitis
Microscopic polyangiitis
UC, PSC, Anti-GBM, Crohn’s
Examples of live attenuated vaccines
BCG
MMR
Influenza (intranasal)
Oral rotavirus
Oral polio
Oral typhoid
Yellow fever
Weakened form of pathogen
NOT for immunocompromised/pregnant
Examples of inactivated vaccines
Rabies
Hepatitis A
Influenza (intramuscular)
Pathogens have been killed by heat/chemicals to elicit immune response
Examples of toxoid vaccines
Tetanus
Diphtheria
Pertussis
Immune system learns to combat the natural toxins the bacteria produce
Examples of conjugate vaccines
Pneumococcus
Haemophilus
Meningococcus
Links poorly polysaccharide immunogenic bacterial outer coats to proteins - more immunogenic
Examples of subunit vaccines
Hepatitis B
Human papillomavirus
Only part of the pathogen is used to generate an immunogenic response
Examples of mRNA vaccines
COVID-19
Introduce a piece of mRNA into cells which then produce a protein to trigger an immune response
Examples of vector vaccines
Ebola and COVID-19
Use a harmless virus (different from the target pathogen) to deliver critical parts of the target pathogen to stimulate an immune response
Different types are available, including whole inactivated virus, split virion (virus particles disrupted by detergent treatment) and sub-unit (mainly haemagglutinin and neuraminidase)
Influenza
Contains HBsAg adsorbed onto aluminium hydroxide adjuvant and is prepared from yeast cells using recombinant DNA technology
Hepatitis B
Contains inactivated Inaba and Ogawa strains of Vibrio cholerae together with recombinant B-subunit of the cholera toxin
Cholera
Example of monovalent vaccines
Measles
Singular antigenic component, conferring immunity against one strain or subtype of a pathogen
Example of polyvalent vaccines
Quadrivalent influenza vaccine
Multiple antigenic components, safeguarding against various strains or subtypes of a pathogen or, occasionally, multiple pathogens
Cavitating lesions, recent flu
Staphylococcus aureus
Alcoholics and diabetics
Klebsiella pneumoniae
Pneumonia in COPD
Haemophilius influenzae
Hyponatraemia, headache, AC exposure, deranged LFTs
Legionella
Associated with CF, green sputum
Pseudomonas aeruginosa
Cold sores, most common type of pneumonia if no specific indications for other types of pneumonia
Streptococcus pneumoniae
TB drugs side effects
Rifampicin - R for Red secretions
Isoniazid - Is for Ice, which would numb you, so neuropathy
Pyrazinamide - Pyra as in Pyramid-like-crystal, so gout
Ethambutol - E for Eyes, so visual problems
Tender lymphadenopathy, usually unilateral, pyrexia and lower back pain (indicative of deep iliac node lymphadenopathy. Anorectal involvement and skin conditions like erythema nodosum are usually associated with it
Lymphogranuloma venereum
Lumbar puncture should be avoided in which circumstances?
Signs of severe sepsis or a rapidly evolving rash
Severe respiratory/cardiac compromise
Significant bleeding risk
Signs of raised intracranial pressure:
Focal neurological signs
Papilloedema
Continuous or uncontrolled seizures
GCS ≤ 12
Avoid dexamethasone in..
Septic shock,meningococcal septicaemia, or if immunocompromised, or in meningitis following surgery
IV dexamethasone should be started no later than ____ hours
12 hours
Tx for Pyelonephritis
Broad-spectrum cephalosporin or a quinolone (for non-pregnant women) for 7-10 days
Tx for Urethritis
Either oral doxycycline for 7 days or single dose of oral azithromycin
Posterior/cervical lymphadenopathy + longer duration of prodromal symptoms
EBV
Isolated submandibular lymphadenopathy + 2-20 days of prodromal symptoms
HSV
Mx of genital warts
Topical podophyllum or cryotherapy
Imiquimod
Perform stool microbiological investigations if:
1) You suspect septicaemia
2) there is blood and/or mucus in the stool or
3) the child is immunocompromised
Management of PCP
Co-trimoxazole
IV pentamidine in severe cases (aerosolized alt.)
Steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)
Develops over weeks. meningeal enhancement or signs of cerebral oedema
Cryptococcal meningoencephalitis
Develops over days, abnormalities in the temporal lobes and inferior frontal lobes
Herpes simplex encephalitis
Calculation of safe dose medication
Lung volumes
MOA of antibiotics
Side effects of ACE inhibitors
Cough
Hyperkalaemia
Side effects of Bendroflumethiazide
Gout
Hypokalaemia
Hyponatraemia
Impaired glucose tolerance
Side effects of CCB
Headache
Flushing
Ankle oedema
Side effects of BB
Bronchospasm
Fatigue
Cold peripheries
Side effects of Doxazosin
Postural hypotension
NSAIDS (substrate) + Fluconazole (inhibitor) = ?
GI ulcers, renal injury
Amitriptyline, clozapine (substrate) + Ciprofloxacin (Inhibitor) = ?
Drugs that cause gynecomastia
DISCO
Digoxin
Isoniazid
Spironolactone (most common)
Cimetidine
Oestrogen
Give examples of type 2 hypersensitivity
Autoimmune haemolytic anaemia
ITP
Pernicious anaemia
Acute haemolytic transfusion reactions
Give examples of type 4 hypersensitivity
Multiple sclerosis
Guillain-Barre syndrome
Graft versus host disease
Give examples of type 5 hypersensitivity
Graves’ disease
Myasthenia gravis
