Med 2 Flashcards
What is the function of the hypothalamus
- Key role in homeostasis = HR/BP, body temp, fluid + electrolyte balance (+thirst) app + body weight, sleep cycle, GI secretions
- Regulates anterior pituitary gland – via releasing hormones, secretes dopamine (inhibits prolactin)
- Synthesis hormones that are released from posterior pituitary
What are the two components of the pituitary gland and what do they release?
- Anterior = ACTH, TSH, GH, LH, FSH, Prolactin
- Posterior = Oxytocin (uterine contractions + breast milk ejection), ADH
Structure of the adrenal cortex and the hormones produced
- Adrenal cortex (3main steroid hormones produced): Zona glomerulosa (-> mineralocorticoids), Zona fasciculata (-> Glucocorticoids) and Zona reticularis (->Androgens)
- Adrenal medulla – ‘fight’ or flight response. Secretes epinephrine or norepinephrine
Cushings disease- the approch to treeatment
- Trans sphenoidal surgery - pituitary tumours
- Bilateral adrenalectomy - adrenal tumours eg, phaeochromocytoma
- Ectopic ACTH - removal of tumour if not metatases, metyrapone, ketoconazole + fluconazole to reduce cortisol secretion
Hyperaldosteronism - what is it briefly
XS Aldosterone production -> increased Na+ and water reabsrption
Rare catelcholamind producing tumours eg, chromaffin cells ocllections of adrenal medulla
Prolactinomas and effects
- High protein levels inhibit GnRH release from hypothalamus causing hypogonadism
- Disrupt inhibitor dopamine release -> hyperprolactinaemia
- Pituitary tumours
Acromegaly - one sentance description
Increased growth hormone release from pituitary gland
Surgery - pituitary gland tumours
What is hypopituitarism and the causes
- Partial or complete deficiency of Ant/Post pituitary hormones. Primary or secondary to pathology. Clinical features depend on disruption to HPA.
- Loss of GH-> LH/FSH -> TSH -> ACTH -> Prolactin
- Pituitary apoplexy = pituitary infarction due to stalk compression
- Sheehan’s syndrome = haemorrhage infarction of enlarged postpartum pituitary due to post partum haemorrhage
- Causes =Compression of pituitary gland bu non secretory pituitary macroadenoma (Most common), pituitary apoplexy, sheehans syndrome, trauma, hypothalamic tumours, iatrogenic radiation, infiltrative eg, sarcoidosis).
Symptoms of Hypopituitarism
- GH = Fatigue, muscle weakness, increase body fat
- LH/FSH = decreased periods/pubic hair, mood changes
- TSH = tiredness, increased weight, dry skin, cold intolerance, constipation
- ACTH – severe tiredness dizziness, nausea + vomiting
- Prolactin = inability to produce breast milk (Sheehan’s)
- ADH = Increased thirst, increased urine
- Patients usually pale to combo of mild anaemia and lack of melatonin
Ix and Mx of hypopituitarism
IX: Hormone profile testing, imaging.
Mx: Treat underlying, replace hormones.
- Baseline Ant pituitary hormone, Serum + urine osmolarity , Dynamic tests – ITT/SST/Glucagon tests
- Pituitary MRI
- Visual fields ass if involvement optic chiasm
- Replace Cortisol BEFORE Thyroxine to avoid triggering Addisonian crisis
- TSH unreliable for monitoring – need to check FT4 + FT3
- Need to replace Cortisol before investigating for DI
Adrenal insufficiency - what is it and the classifications
Adrenal Insufficiency: Classified as primary, secondary or tertiary and reaults from disorders that affect the adrenal cortex (eg, Addisons, Congenital adrenal hyperplasia), the anterior pituitary gland (eg, pituitary tumour or subarachnoid haemorrhage), or the hypothalamic (eg, HPA axis suppression). Acute adrenal failure is Addisons disease
•Primary adrenocortical insufficiency (Addison’s) – destruction of adrenal cortex leads to glucocorticoid (cortisol) and mineralcorticoid (aldosterone) deficiency . Causes are mostly autoimmune but others are TB, adrenal mets, lymphoma, opp infections. 30-50years. Often ass with Virtilligo.
•Secondary adrenal insufficiency – Caused by pituitary or hypothalamic disease -> decreased ACTH secretion -> adrenal failure. Most common cause iatrogenic from prolonged steroids. Commonest cause iatrogenic due to long term steroid therapy leading to suppression of pituitary adrenal axis.
Addison disease causes and RF
Autoimmune disease, TB, Adrenal mets, lymphoma, haemorrhage (WF syndrome), opportunistic infections in HIV.
•RF – Female, adrenocortical autoantibodies, adrenal haemorrhage, autoimmune disease
Signs and symptoms of Addison’s disease
•Sings/ Symptoms – Fatigue, Anorexia, Weight loss, Nausea/ vom. Hypotension, arthralgia + myalgia. Hyperpigmentation
Invetsigations for addisons disease
•– Cortisol measurements, ACTH stimulation test (short/Long synacthen tests), U&E, glucose, autoantibodies, renin/aldosterone, CXR + AXR, 21 hydroxyls auto antibodies (positive in some auto immune disease), Hypercalcaemia + anaemia.
Management for Addison’s disease
- Replace glucocorticoid and mineralcorticoids
- Acute – Hydrocortisone IV 100mg immediately then 200mg over 24hours either by continuous IV infusion or by 50mg iV every 6hours
- Fluid resuscitate with 0.9% sodium chloride. Continue iV fluids for next 24-48hours
- Convert to oral glucocorticoids once stable.
- Non acute – systemic glucocorticoid therapy
How to assess and manage someone with Addisonian Crisis
- Medical emergency.
- Shock/hypotension, abdo pain, fever, hypoglycaemia, severe atigue, hyponatraemia
- Ix = U+E, Glu, cortisol, ACTH,TFTs, Glu.
- Mx = IVT with 0.9%saline, Give IV/IM Hydrocortisone 100mg if suspected, patient may require QDS IV Hydrocortisone util able to switch to PO tablets. Treat hypoglycaemia if present with 5% glucose infusion. Treat udnelryign cause
Assess and manage patients with hypovalaemic shock
- Hypovalaemic shock = volume of circulatory system is inadequate for perfusion of organ tissues
- Shock = acute circulator failure with inadequate O2 delivery. Leds to organ dysfunction, end organ damage and death
- Diagnostic indicator = Hypotension, Tachycardia, Skin changes, Oligura
- IX = Lactate + urine output, NEWS/OBS, Glucose, VBG/ABG, FBC, CRP, BC, ESR, WBC
- Mx = O2 + vasoactive agents, IV access (crystalloid fluids like Hartmann’s), analgesics, treatment of underlying cause
Cushings SYndrome VS Disease
- Cushings syndrome is adrenal excess
- Cushings disease is a specific type of cushings when pituitary tumour causes body to make too much cortisol
Cushings syndrome - what is it and the 2 main classifications of cause
- Pathophysiology = Caused by prolonged exposure to either endogenous or exogenous glucocorticoids.
- ACTH Dependent – excessive ACTH from pituitary gland (Cushing’s disease) or ectopic ACTH secretion (SCLC + carcinoid tumours)
- ACTH Independent – Adrenal cortisol excess (adrenal tumours/adenomas) or exogenous steroids.
What are the DDX of cushings
Hypothyroidism, depression, PCOS, T2DM
History and symptoms of Cushings
- S/S = Upper body obesity with thin limbs, skin problems (acne + plethora), high BP, muscle./boen weakness, moodiness, high blood usgars, tachycardia.
- History = PMG (obesity, diabetes), medications (long term steroids/frequent steroid courses)
RFs of Cushings syndrome
•RFs = Adrenal or pituitary tumours, long term therapy with corticosteroids and being female.
Management of Cushings syndrome
- Iatrogenic – stop meds
- Cushings disease – remove pituitary adenoma, bilateral adrenalectomy, possible radiotherapy
- Adrenal adenoma/ carcinoma – adrenalectomy
- Ectopic ACTH –s urgery to remove tumour if no mets
- Medis – Metyrapone, ketonconozole, fluconazole
Invetsigations of Cushings sundrome
•= 24hour urinary cortisol. Late night salivary cortisol (elevated due to loss of diurnal variation), overnight dexamethasone suppression test (AM cortisol). Helps identify excess hypercortisolaemia but does not identify the cause. Scans are CT chest (ectopic ACTH) or abdo, MRI adrenals, MRI pituitary
What is pseudo cushings
•– clinical features + biochemical evidence of cortisol excess but not caused by hypothalamic pituitary axis (depression, alcohol excess, obesity).
What are the complications of cushings syndrome
•Hypertension, Diabetes, Osteoporosis (reduces bone formation), prone to infections (suppressed immune system) . Cortisol does have mineralocorticoid activity so can cause electrolyte abnormalities (ihgh Na+, low K+, high BP).
Thyroid Function Tests - what are the categories and how to interpret
- Look at Free T3/T4.
- In any systemic illness, TFTs can be deranged and all low.
- Thyroid autoantibodies – Antithyroid peroxidase (TPO) or antithyroglobulin Abs nay be increased in autoimmune thyroid disease, Hasimoto’s or Graves.
- TSH receptor antibody – Mya be increased in Graves
- Serum thyroglobulin – used for monitoring treatment carcinoma and detecting facticioushyperthyroidism
- US – distinguishes cystic from soli (Poss malignant) nodules.
- Isotope scan – for cause and detect retrosternal goitre thyroid metastases etc.
How is the Thyroid controlled
What is subclinical hypo and hyperthyroidism
Subclinical hypothyroidism: TSH high, Normal T4/T3 and no symptoms. Risk progression.
Subclinical hyperthyroidism: Decrease TSH, normal T4/T3.
What imaging to do you for the thyroid
Imaging in Thyroid: US (good for size + structure, FNA, scoring), CT scan and isotope scanning (structure + function)
Thyroid storm - describe this thyroid emergency - RFs, clinical features,
- Thyroid storm: rare, potentially life threatening. 30-50% mortality.
- RFs = acute infection, post partum, withdrawal of ATDs, recent surgery or RAI, radiographic contrast agents
- Clinical features = altered mental state, severe hyperthyroid signs, vomiting, diarrhea, jaundice, pyrexia, tachycardia/tachyarrhythmia
- Multisystem decompensation = cardiac failure, congestive hepatomegaly, resp distress, dehydration+ pre-renal failure
- Tx = Betablockers, steroids, ATDs
Myxoedema coma - thyroid emergency
•Myxoedema Coma: Extreme hypo
- Profound Hypothyroidism, Hypothermia, hyporeflexia, hypoglycaemia, bradycardia, seizures
- Cardiomegaly + pericardial effusion, cerebella ataxia
- Psychiatric symptoms (depression/psychosis), hyponatreamia, treated with IV Liothyronine (T3)- caution IHD.
Describe Thyroid hormone synthesis
- Thyroid follicles is location
- Iodine converted to I- by enzyme TPO
- I- then attaches to tyrosine units of thyroglobulin
- Proteases cleave T3 + T4 under regulation of TSH
- In peripheral tissue de iodinases allow for conversion of T4->T3 (mor eptoent)
- T3 hormone is able to affect transcription
- T3 has greatest effect on neg feedback
- TRH -> TSH -> T4 + T3
Hyperthyroidism - what is it and the sysmptoms and signs
•Hyperthyroidism is increased thyroid hormone synthesis and secretion specifically from disorders of thyroid gland so excess T3/54 and compensatory decrease in TSH. Unless ademona then increase TSH and increase T3/T4.
•Symptoms: Diarrhea, decreased weight, increased appetite, over active, sweats, heat intolerance, palpitations, tremor, irritability, labile emotions, oligomenorrhoea +/-infertility. Rarely psychosis, chorea, panic, itch, alopecia, urticaria.
•Signs: Pulse false/irregular, warm moist skin, fine tremor, palmar erythema, thin hair, lid lag, lid retraction. May be goitre, thyroid nodules.
Tests for Hyperthyroidism
•Tests: Decreased TSH,/T4 and increased T3. May be mild neutropenia (Graves)< Increased ESR/Ca+/LFTs. Check thyroid autoantibodies, isoptopescan and test eyes.
Causes of Hyperthyroidism
•Causes: Graves disease, Toxic multinodular goitre, Toxic adenoma, Ectopic thyroidtissuem Ecogenous.
Treatment fo hyperthyroidism
1.Drugs: B blockers (eg propranolol) for rapid control symptoms. 2 strategies of Anti thyroid meds. In Graves maintain either 12-18 tgen withdraw. Watch for agranulocytosis with carbimazole. Titration eg, carbimazole PO for 4wks then reduce according to TFT every 1-2m .Block replace: Carbimazole + levothyroxine together.
2.Radioiodine: Most become hypothyroid after. No ev for increased cancer, birth defects or infertility. Caution inactive hyper as risk of thyroid storm
3.Thyroidectomy: usually total but risk of damage to recurrent laryngeal nerve (hoarse voice) and hypoparathyroidism. Patients will beom hypothyroidism so thyroid replacement needed
4.In pregnancy + infancy: Get expert help.
Compications in Hyperthyroidism
Complications: Heart failure, angina, AF, osteoporosis, opthalmopathy, gynaecomastia.
Increase in BMR -> Hyperthyroidism -> weight loss
Causes of hyperthyroidism
- Graves diseases
- Toxic Multinodular goitre: In elderly and in iodine def areas. Nodules that secrete thyroid hormones. Sugrery indicated for compressice symptoms from enlarged thyroid
- Toxic adenoma: Solitary nodule producing T3 &T4. On isoptope scan, the nodule is ‘hot’ and rets of gland suppressed.
- Ectopic thyroid disease: metastatic follicular thyroid cancer, or struma ovarii: ovarian teratoma with thyroid tissue
- Exogenous: Iodine excess eg, food contamination, contrast media. Levothyroxine excess cusesIncrease T4/D T3/ D thyroglobulin. Also Subacute de Quervain’s thyroiditis (self limiting post viral with painful goitre, Increase temp, +/- Increase ESR + low isotope uptake on scan), Drugs (amiodarone lithium), postpartum, TB.
WHat are the signs and triggers of graves disease
- Signs: Eye disease (exophthalmos, opthalmoplegia), Pretibial myxoedema, Thyroid acropachy (clubbing, painful finger + toe swelling…
- More males, typical 40-60. Cause is circulating IgG autoantibodies binding to and activating G coupled thyrotropin receptors, which cause smooth thyroid enlargement and increased hormone production and react with orbital autoantigens.
- Triggers – stress infection, childbirth. Parents often hyperthyroid. Associated with other autoimmune diseases (Vitiligo, T1DM, Addison’s,
What are the causes of hypothyroidism?
- Primary autoimmune hypothyroidism - primary atorphic and Hashimotos thyroiditis (goitre).
- Primary hypoT - Iodine deficiency, post-thyroidectomy or radioiodine treatment, drug induced 9antithyroid drugs), subacute thyroiditis (temp hypoT after hyperthyroid phase).
- Secondary hypoT - not enough TSH (hypopituitarism)
Hyponatraemia - def, causes, clinical features
- Serum Na+ <135
- XS water compared to electrolyts so low plasma osmolarity
- Causes: Increeased reabsorption (Cirrhosis, CHF, Nephrotic syndrome), Reduced excretion (SIADH), Salt def (renal/non renal loss)
- clinical = Water excess - from brain injury(confusion, headache, seizures), Hypervolaemia confined to ECG so oedema + fluid overload, salt def present with hypovolaemia + tachycardia with postural hypotension.
Investigations and treatment for hyponatraemia
Ix = rine Na+ (response of kidneys to low Na+ in blood), TFT (hypothyroidism), Cortisol (Addison’s), Glucose (hyperglycaemia-DKA often), Urine and serum osmolarity (mainly determined by Na+), serum one automatically low), LFTs.
Tx:
- salt deficient – iv saline
- XS fluid – fluid restriction (500-750ml/24h)
WHta are the causes, def and treatment of SIADH
- Causes: Tumors, chest disease, metabolic, CNS disorders,, drugs, idiopathic
- Dx criteria: Decrease Na+ serum osmolarity <270, inappropriate urine osmolarity, excess renal sodium loss >30, absence clinical evidence of hypovolaemia or fluid overload, normal renal/adrenal/thyroid function.
- Tx: Treat underlying cause, fluid restrict (500-700ml/24hr), drug Tx (demeclocycline-induces partial nephrogenic DI, and vasopressin V2 receptor antagonist Tolvaptan promotes aquapheresis but expensive). Saline infusion in emergency (vom/sizures/GCS<8/CR distress, 150ml 3%saline over 20mins, aim for initial rise 5mmol/L.
What is Cerebral salt wasting
- Potential cause of hyponatremia in CNS disease. Hyponatremia and ECF depletion from inappropriate sodium wasting in urine.
- CSWS- low blood sodium conc and dehydration in response to injury or tumor’s surrounding brain.
Hypernatramia - cause, def, complications and Tx
Serum Na+>145mmol/L
- Usually from loss of water in excess of loss of Na+. Caused by vomiting, diarrhea, diuretics,diabetes,iV hypertonic saline, IV NaHCO3, DI, Cushing’S.
- Complications: seizures, subdural+intracranial haemorrhage, ischaemic stroke, dural sinus thrombosis.
- Use 0..9% IV saline to replace volume – 1L over 8-12hrs. Swithc to 0.45% saline or 5%glucose once euvolaemic
- Ix = U&Es, glucose, urea and creatinine, urine + serum osmolarity
What is Hyperkalamia and the causes
K+ >5.5mmol/L
Causes:
- Decrease renal excretion – AKI/CKD/ K Sparing diuretics (spironolactone)
- Cell injury – rhabdomyolysis/burns/blood transfusion/tumor cell necrosis
- K+ cellular shifts – acidosis/drugs (suxamethionium)/ Tumour cell necrosis
- Hyperaldosteronism – Addison’s/ drug induced (NSAIDs/ACEi)
- Spurious
What are the symptpms and ECG changes with Hyperkalaemia then how to do manage these
- Clinical = muscle weakness and cramps; paraethesia, hypotonia, focal neuro deficits. Oft asymptomatic.
- Mx =Review ECG, 10% calcium chloride to stabilize myocardium, IV glucose/insulin infusion to bring K+ into cells. Treated fluid deficiency and underlying cause eg, Addison’s disease
Hypokalaemia - def, causes
- K<3.5
- •Causes – alcohol excess/ CKD/ Diuretics/ DKA/ Diarrhea/ LaxatiVes/ vomiting/ primary hyperaldosteronism/ Cushing’s syndrome
Symptoms, ECG and treatment of hypokalaemia
- Symptoms = May cause lethargy, weakness, leg cramps
- ECG- flatted T waves and prominent U waves, QT prolongation
- Treat = replace. PO potassium chloride if mild. Iv fluids with KCI if severe
- Correct Mg deficiency if present in patients with severe hypokalaemia.
Hypercalcaemia -
•Symptoms = Renal (polyuria, polydipsia), GI (anorexia, vom, consitpaiton, abdo pain, gastric ulcers, pancreatitis), CNS (confusion, lethargy, depression), other (pruritis, sore eyes). Also consider bone pain, fracture, hematuria, loin pain (renal stones).
•Causes = hyperparathyroid (1/3ry), malignancy (humoral hypercalcaemi, multiple myeloma, bony mets), vit D toxicity, BFHH, Sarcoidosis + other granulomatous disease, drugs (thiazide diuretics, lithium), immobialisation, hyperthyroidism, renal failure, Addison’s, vit A toxicity.
•Mx = Check vit D, PTH, TFTs. IVT 0.9% saline, steroids (prednisolone, dexamethasone and IV Zolendronic acid.
Hypocalcaemia - causes
- Ca2+ homeostasis controlled by PTH + Vitamin D levels.
- Causes: Hypoparathyroidism, vitamin D deficiency,, hypomagnesium
- Ca2+ homeostasis: Calcitriol – Released when blood plasma (Ca2+) = low, increases Ca2+ bone resorption, absorption of Ca2+ from small intestines.
What are the 2 main lineages in haematopoiesis
Lymphoid or myeloid
What is anaemia and what symptoms and signs might your expect
Anaemia = Low haemaglobin conc which may be due to low red cell mass or increased plasma volume. Low Hb is <135men, <115 women.
- Symptoms – due to underlying cause or anaemia itself: fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia.
- Signs – may be pallor, signs hyperdynamic circulation (eg tachy), flow murmurs, cardiac enlargement nad later HF.
What types of anaemias are associated with Low/Normal/High MCV
- Low MCV = Iron def, thalassaemia, sideroblastic
- Normal MCV = acute blood loss, anaemic chronic disease, bone marrow failure, renal failure, hypothyroidism, haemolysis, pregnancy
- High MCV = B12 or folate def, (can alter DNA synthesis) alcohol excess (or liver disease), reticulocytosis, cytotoxics, myelodysplastic syndromes, marrow infiltration, hypothyroidism. Antifolate drugs. Pernicious anaemia(autoimmune)
- Haemolytic anaemias = don’t fit in above classification . Suspect if reticulocytosis, mild macocytosism decrease haptoglobin, increase bilirubin/LDH/urobilinogen. Often mildly haundiced.
- Applastic anaemia - Caused by reduction in pluripotent stem cells so reduce all cell types.
What causes iron deficiency anaemia and how mgiht you present
- Causes = Excessive blood loss (menorrhagia, colon cancer, post menopausal), inadequate dairy intke, poor intestinal absorption (coeliac), increased requirements
- Signs = Chronic IDA (koilonychia, atrophic glossitis, angular cheilosis and rarely post cricoid webbs).
- Symptoms = Fatigue, SOB, Palpitations, pallor, nail changes, hair loss, atrophic glossitis, angular stomatitis.
What are the investigations for iron def anaemia
- Blood film: microcytic, hypochromic anaemia with anisocytosis + poikilocytosis.
- Decrease MCV/MCH/MCHC. High tIBC (relflects low iron stores)
- Confirmed by decreased ferritin (acute phase protein which also increases with inflamm/malignancy.)
- Check coeliac serology – if neg and not menstruating need urgent olonscopy and gastroscopy.
- Endoscopy to rule out malignancy in unexplained.
Treatment for iron deficiency anaemia
- Orla iron e,g ferrous sulphate but SE nausea/abdodiscomfort/constipation/diarrhea/ black stools. Hb should raise 10 a week. Continue till at least 3m after normalizes to replenish stores.
- IV iron only if oral ineffective or impossible.
- Check compliance
WHta can anaemia of chronic disease arise from?
How to test and how to treat?
- Arises from 3 problems: Poor use iron in erythropoiesis, Cytokine induced shortening od RBC survival and Decrease production to and response to erythropoietin.
- Causes: Chronic infections, vasculitis, rheumatoid, malignancy,r neal failure…
- Tests: ferritin normal or increased in mild normocytic or microcytic anaemia. Check blood film, B12, folate, TSH, and tests for haemolysis.
- Treatment – Underlying disease and erythropoietin.
Sideroblastic anaemia - what is this and when do you consider it?
: Red cells fail to completely form haem, whose biosynthesis takes place partly in mitochondrion. So deposits of iron in mitochondria that form ring around nucleus.
- Think about this when microcytic and not responding to iron. Characterised by ineffective erythropoiesis, leading to increased iron absorption, iron loading in marrow and possible haemosiderosis (endocrine, liver and heart damage from iron deposition).
- Causes: Congenital (rare, x linked), or acquired eg, idiopathic eg myelodysplastic disease, follow chemo, alcohol…).
- Tests: look for increase ferritin, hypochromic blood film and disease defining sideroblasts in marrow.
- Treatment: remove cause. Pyridoxine and possible repeated transfusions for severe anaemia.
Different types nutrition
- Enteral nutrition – If gut working normally then preferred way.
- By mouth – nutritional products
- Through tube (NG/NJ…)
- Parenteral nutrition – if gut cant absorb nutrients then deliver to bloodstream through drip.
- PEG tube – feeding tube through skin and stomach wall.
Describe te glomerulus and its function
Glomerulus = loop of capillaries surrounded by bowman capsule.
- Filtration barrier has 3 layers: Endothelial cells, basement membrane + podocytes of bowman capsule
- Ultrafiltration = 1st stage in urine production occur here.
- Afferent arteriole dilation + efferent arteriole constriction -> pressure gradient allowing filtration across barrier.
- Nephortic syndrome = proteinuria, hypoalbuminaemia + oedema. Minimal change disease (podocyte pathology) is most common cause.
- IgA nephropathy – IgA mediated inflammation
Descrieb the PCT and the function
- High capacity for reabsorption, has epithelial cells, large channels for ion transport.
- Pars convolute + pars recta
- Reabsorption via paracellular + transcellular transport
- Na+ drives reabsorption of other substances eg, water, glucose
- Secretion_ substances removed from blood in PCT.
Descrieb the Part sof the Loop of henle and their function
Absroption of Na+
- Thin DL - highly permeable to water – water reabsorption occurs driven by counter currently multiplier system
- Thin AL – Impermeable to water, reabsortopn of Na+ and Cl-
- Thick AL – primary site of Na+ reabsorption and impermeable to water – NKCC2 transporter
bartter syndrome
Bartter syndrome: autosomal recessive disease -> mutations in NKCC2, K+/Cl- channels -> hyponatraemia, hypokalaemia + metabolic alkalosis.
Early DCT - cells here + urpose
Early DCT: Impermeable to water, reabsorption of Na+,Cl-, Ca2+. NC channel transporter
•Macular densa cells as part of tubuloglomerular feedback to regulate GFR + blood flow
Late DCT and cells here
Late DCT: mostly principal cells + intercalated cells.
- Principal cells – Na+ uptake + K_ excretion driven by ATPases + EHaca
- Intercalated cells – control H+ and HCO3- conc.
Colelcting fuct function
Collecting duct: ADH + aquaporins to assist in reabsorption of water
•ADH: binds to V2 receptors -> adenylate cyclase -> cAMP -> vesicles containing aquaporin channels insert into apical membrane -> increased water reabsorption.
Diabetes insiidus
Polyuria + polydipsia. Insufficient ADH/ lack of response of collecting ducts to ADH. Less water reabsorbed formf iltrate -> increased volume of filtrate ->increased urine volume. Water deprivation test to confirm diagnosis.
SIADH effect of kidney nephron
SIADH: XS ADH released -> increased aquaporin expression in CD -> water retention. Dilution of blood -> Lowers Na+ -> hyponatraemia. Can be caused by ectopic ADH (paraneoplastic) from SCLC.
Npehortic syndrome - what is it and why does it happen?
•Def = Triad of proteinuria >3g/24h, Hypoalbuminaemia usually <30g/L, oedema.
•Aetiology = Primary renal disease (membranous nephropathy(adults), focal segmental glomerulosclerosis, minimal change disease(kids)) . Secondary to systemic disorder (DM, lupus nephritis, myeloma, amyloid, pre-eclampsia, infections, genetic conditions, some allergic reactions. In young person thin about autoimmune renal disease.
•Patho = Filtration barrier of the kidney is formed by podocytes, the glomerular basement membrane and endothelial cells. Portein uria results form podocyte patho, abnormal function in minimal change disease, immune mediated damage in membranous nephropahy and podocyte injury/death in FSGS or patho in GBM/endothelial cell, membranoproliferative GN.
Presentation and DDx of nephrotic syndrome
- Presentation = Generalized, pitting oedema, which can be rapid and severe. Look in dependent areas and those of low tissue resistance. Ask about systemic symptoms eg joint, skin. Consider malignancy and chronic infection.
- DDx– minimal change nephropathy, FSGS, membranous nephropathy, diabetic nephropathy, primary glomerula disease,s, fibrillary glomerulopathues, lupus neprhtitis and multiple myeloma.
Ix of Npehortic syndrp,e
•24hour urine collection+ urine dip . Obs, DO bloods (FBC, U&Es– high urea poss, high creatinine,high K+, poss kidney US for DDx, poss renal biopsy. Check triglycerides and cholesterol as these are complications.
Mx of nephrotic syndrome and complications
: if secondary think about lifestyle control, DM etc. refer to nephrologist.
- Reduce oedema: Fluid and salt restriction. Diuresis with lop diuretics eg, furosemide. Aim 0.5-1kg weight loss per day to avoid IV vol depletion + secondary AKI Thiazide diuretics can be added.
- Treat underlying disease: Renal biopsy in adults and in children steroids induce remission in most unless no response to steroids or clinical feature suggesting another cause then biopsy. Uuslaly biopsy as last effort if unclear why
- Reduce Protein uria: ACEi/ARB reduce proteinuria (may not be needed)
- Complications: Thromboembolism, infection, hyperlipidaemia, acute renal failure as hypercoagubale. Can also get malnourished if dotn eat due to it.
Diabetic npehorpathy - what is it, symptoms, tests and how to treat
- Diabetic nephropathy.- kidney damage caused by diabetes (kidney disease).high blood glucose damages the small blood vessels and tiny filters in your kidneys so they leak and don’t work as well. Abnormal amounts protein from blood can leave your body in your urine.
- Symptoms = Swollen ankles/feet/hands, blood in pee, fatigue, SOB, feeling sick.
- Tests = Urine test (ACR), blood test (eGFR)
- Treat = BP under control 9ACEi/ARBs),might need avoud some foods, latest option is kidney transplant.
What is chronci kidney disease, causes and classification
- Def = Abnormal kidney structure of function, present or >3m with implications for health.
- Classification = Based on GFR category, presence albuminuria as marker or kidney damage, and cause of kidney disease. The lower the GFR and albuminuria associated with higher mortality, CV mortality, kidney failure, AKI.
- Most common causes = Diabetes, glomerulonephritis, Increased BP/renovascular disease
CKD invetsigations
- Bloods – U&Es, Hb, (normochromic, normochytic anaemia), glucose (DM), Decrease Ca and increase PO4^3-/PTH). Directed iinvetsiagtions Urine – Dipstick, MC&S, A:CR, P:CR, Bence jones
- Imaging – USS and exclude obstruction.
Histology: Consider renal biopsy in progressive disease, nphrotic syndrome, systemic disease, AKI without recovery. Unlikely to change treatment if GFR stable and P:CR
Treatment of Chronic kidney disease
- Appropriate referral to nephrology:
- Treatment to slow renal disease progression: Target BP (<140, <90), RAAS (ACE-i/ARB for DM/HBP/CD with high A:CR), Gkycaemic control, Lifestyle
- Treatment of renal complications CKD: Anaemia, acidosis (conside sodium bicarb supplements), oedema (restrict fluid + sodium intake- may need loop diuretics), CKD bone mineral disorders (as increase serum phosphate, reduced hydroxylation vit D by kidney), restless legs/cramps, Diet.
- Treatment other complications CKD: CV disease (antiplatelets, atorvastatin…)
- Prep for renal replacement therapy (dialysis/transplantation):All suitable ones should be listed for deceased donor transplantation 6m before anticipated start RRT.
Glomerulnephritis - what is it and how to IX and MX
•Glomerulonephritis = term that encompasses conditions which are caused by pathology in glomerulus; present with proteinuria haematuria, or both; diagnosed on renal biopsy, cause CKD, can progress to kidney failure
•Investigations: Assess damage + potential cause
•Bloods – FBC. CRP, U&E, LFT, immunoglobulins, electrophoresis complement, autoantibodies, blood culture, ASO, hepatitis serology
•Urine – MC&S, Bence Jones protein; A:CR/P:CR, RBC casts
•Imaging – CXR (pulm haemorrhages), renal US
•Renal biopsy: For diagnosis – Exam of glomerular lesions provides GN diagnsosi. Includes proportion glomeruli involves, how much, hypercellularity, sclerosis/ Electron microscopy for ultrastructure, immunhisotlog
•Mx – Gen management is BP control and inhibition of renin-angiotensin axis, Specific is immunosuppression etc.
Nephritic vs nephrtoic syndrome
•Nephrosis (proteinuria due to podocyte patho) or Nephritis (haematuria due to inflammatory damage). If GN causes scaring, can get proteinuria which can cause complications.
Nephritic glomerulonephrtitis- causes
•Proteinuria due to podocyte pathology
- IgA nephropathy: Asymptomatic non visible hematuria or episodic visible haematuria which may be ‘; within 12-72h infection. Increase BP. Protein uria, slow indolent disease. Diagnosis by renal biopsy (IgA deposition in Mg). Treat with ACE-i/ARB reduce proteinuria + protect renal function.
- Henoch-Schönlein Purpura (HSP): Small vessel vasculitis + systemic variant IgA nephrophathy with deposition of IgA in skin, joints alongside kidney. Purpuric rash on extensor surfaces, flitting polyarthritis, abdo pain, nephritis. Usually clinical Dx, confirmed with positive IF or igA and C3 in skin. Renal biopsy identical to igAnephropathy. Managed same as above but steroids for gut involvement.
- Post-Streptococcal GN: After throat or skin infection where streptococcal antigen deposition in glomerulus leading to immune complex form and inflammation. Varies haematuria to acute nephritis, (increase BP/oliguria… EV streptococcal infection, need supportive antibiotics
- Anti-glomerula basement membrane disease: rare. Autoantibodies to type iV collagen. Presents with renal disease and lung disease. Anti-GBM for Dx, nee dplamsa exchange, corticosteroids and cyclophosphamide.
- Rpaidly protessive GN – Breas in GBM allow inflx inflammatory cells etc so cresecents seen on renal biopsy. Need corticosteorids and cyclophosphamide.
What are the vitamin K dependent clotting factors
2,7,9,10
What is DIC
•in severe systemic illness, dying cells release procoagulant agents that activate coagulation resulting in fibrin generation that occludes small vessels , platelets and clotting factors are used up and result in bleeding elsehere. Blood tests reveal thrombocytopenia, increased PT/INT and APTT, and raised D-dimer and fibrin degredation products. Treat by removing cause and supportive therapies (blood, platelets, FFP, cryoprecipitate).
Why might lvier coagualtion be impaired
•Coag impairment – Mechanistic: Chronic liver disease (cirrhosis/Malnutrition), acute liver failure, biliary patho (cholestatic liver disease).
Describe the structure of the liver and cells
- Liver = 2 major lobes separated by falciform ligament and surrounded by Glisson’s capsule (fibrous CT). Within liver sinusoids are O2 poor and nutrient rich blood from portal vein and mixes with O2 blood from hepatic artery. From sinusoids, blood enters system of veins that converge forming hepatic veins. Enter IVC.
- Endothelial cells separated from hepatocytes by sub endothelial space (Space of Disse/ Perisinusoidal sac).
- Blood passes through endothelial wall to have intimate contact with hepatocyte surface facing perisinusoidal space
- Proteins made by hepatocytes transferred to blood by perisinusoidal space
What is jaundice and the 3 maint ypes
- Jaundice: Unconjugated BR is insoluble in water (only travels in blood if bound to albumin) and conjugated is soluble in water.
- Prehepatic jaundice – Increased haemolytic -> increased unconjugated BR
- Hepatic jaundice: Liver impairment. Decreased ability of liver to conjugate bilirubin so both UN and conjugated in blood
- Post hepatic jaundice: Blockage of bile duct resulting in back flow of conjugated BR into blood.
Descrieb the production of bilirubin
What the main LFTs and intepretation
- ALT - Hepatocyte.
- AST - Hepatocyte
- Prothrombin time - synthetic function
- ALbumin - synthetic function
- GGT, ALK P - outflow function (cholangiocytes)
Functions of the liver
- Glucose metabolism
- lipids - uptake, synthesis, pacakging
- Portein and amino acids- anabolism
- secretion of bile
- Sotrage fo Vitsmin A,D,B12,Cu, Fe
- Haematolgoical fucntion - phagocytosis, hemopoiesis
What is the primary epithelial cell in the liver
Hepatocytes
Kupfer cells
reisdent macrophages
SInusoidal cells
Specialised endothelial barrier functions
What are some coagualtion disorders that can cocur in liver disease
- Unable to absorb Vitamin K : Obstructive biliary disease -> impaired clotting
- Hepatocyte damage: Reduced clotting factors of intrinsic + extrinsic pathway.
- Platelets: hypersplenism can reduce platelets
- Biliary: Cholestatic obstructive disease: blockage of bile ducts -> reduced vitamin K absorption -> prolonged clotting time
- Thrombocytopenia
- DIC: Systemic illness where cells release procoagulant agents -> fibrin deposition -> vessel occlusion.
- Bleeding in liver disease: Less absorption of vitamin K, vitamins ADEK (fat soluble) and need bile. Less sysnthesis of other lcotting dactors, low platelets, reduced levels protein c and S. Less fibrinogen, endothelial dysfunction
Classify liver disease into 2
- Acute liver failure: Fulminant liver failure, uncommon but life threatening. Most commonly due to paracetamol toxicity in UK and acute viral hepatitis world wide. Presents with jaundice, encephalopathy and coagulopathy. Ascites uncommon, might need liver transplant. Coagulopathy/Hepatic encephalopathy/acute liver injury
- Chronic liver Disease: Progressive destruction and regeneration of liver parenchyma and regeneration of liver parenchyma leading to cirrhosis and fibrosis. Cirrhosis is final common pathway for wide variety of insults to the liver. Often asymptomatic until late stage. Mostly from alcohol liver disease, chronic viral hepatitis or non alcoholic fatty liver disease.
Gastr-oeosphageal varices - what are these and the RF, sympotms
- Abnormal, enlarged veins in the tube the osophagus. Most have chronic liver disease.
- RF = Increase portal pressure, variceal size, endoscopic features od variceal wall and advanced liver disease.
- Symptoms – haematemesis, melaena, abdo pain, dysphagia/odynophgia, confusion
- Signs – Peripherally shut down, pallor, hypotension + tachycardia), reduced urine output, melaena, signs chronic liver disease, reduced GCS, signs sepsis.
Invetsiagtions and management of Oesophageal varices
- Ix – FBC, INR, renal function, LFTs, BUN, group and cross match, hepatic serology, CXR, ascitic tap
- Imaging – CT/MRI-a, IS, doppler sonography, video capsule endoscopy, hepatic vein pressure gradient, transient elastography
- Mx – Band ligation for UGIB from varices, TIPS considered if not controlled by bands, stent insertion when other failed
Causes of portal hypertension
- Preheptaic – thrombosis (portal ro splenic)
- Intrahepatic – cirrhosis, schistosomiasis, sarcoid, myeloproliferative diseases, congenital hepatic fibrosis
- Post hepatic – Budd-Chiari syndrome, RHF, constrictive pericarditis
Alcoholic liver disease - the stages
- Fatty liver – Build up of fat inside liver cells. Leads to an enlarged liver. It’s the most common alcohol-induced liver problem. Often no symptoms, but might get tired/weak/weight loss.
- Alcoholic hepatitis – Acute inflammation of the liver. Death of liver cells, often followed by permanent scarring. Pian over liver, fever, weakness, nausea & vomiting, appetite loss, jaundice.
- Alcoholic cirrhosis – Destruction of normal liver tissue. It leaves scar tissue in place of working liver tissue. Portal hypertension, enlarged spleen, poor nutrition, bleeding in intestines, ascites, kidney failure, confusion, liver cancer.
- Dx – Bloods (LFTs), Liver biopsy, US, CT scan, MRI
- Rfs – high alcohol intake, binge drinking, female gender, genetic
What is alcohol dependency and signs of this
- Alcohol dependency = Chronic medical condition that typically includes a current or past history of excessive drinking, strong craving for alcohol, continued use despite repeated problems with drinking and an ability to control alcohol consumption.
- Patient – malaise, increase TPR, anorexia, D&V, tender hepatomegaly, possible jaundice, bleeding, ascites
- Blood – Increase WCC, decrease platelets, Increase INR, Increase AST, Increase MCV, increase urea
- Jaundice, encephalopathy or coagulopathy is severe hepatitis.
How to assess risk of alcohol dependency
- Assessing risk – AUDIT-C: How often do you have a drink containing alcohol, how many units of alcohol do you drink on a typical day when you are drinking and how often if more than 6(female), more than 8 (male) on single occasional in last year.
- 0-4 lower risk, 5-12 watch out. Possible referral if 11/12.
- Advised not more than 14 units a week and spread over 3days or more if you are doing so.
Alcohol withdrawal syndrome - pathology and symptoms
- AWS = sudden cessation or reduction in usual intake after long term use of alcohol, varies in severity and may represent medical emergency. Need effective Mx early. Not directly related to intake.
- Imbalance in NT in brain caused by chronic consumption (GABA-inhibitory), NDMA (excitatory).
- Alcohol acts on GABA receptors so I hibitory effects so to maintain homeostasis with downregulate GABA neurons + upregulate NDMA.
- On cessation then imbalance NTs so hyper-excitability so AWS. Only drop alcohol levels required so still can have symptoms despite detectable blood alcohol level.
- Minor symptom – Anxiety, insomnia -> Hallucinations -> seizures (as early as 2hours after) -> delirium tremens (agitation, tachyc, fever, hypertension – peak 5days-7days).
- Clinically evaluate risk of thiamine deficiency = PIC
Wernickes encephalopathy
- Wernicke’s Encephalopathy = consequence thiamine Vit B1 def (essential coenzyme in biochem pathways). As this develops -> enzymes, system dependent on thiamine function less well and cell death. Can lead to permanent brain damage if not treated.
- Give IV pabrinex before dextrose (glucose) = so glucose more likely to utilize pabrinex to form ATP or else only increase lactic acid produced.
- CIWA = Clinical institute withdrawal assessment – 10- item scale to measure severity alcohol withdrawal syndromes.
Management of alcohol withdrawal syndrome?
- Mx:Most hospitalize, catheter, CVP monitor, screen infections, stop alcohol consumption (can use chlordiazepoxide for withdrawal stuff or lorazepam, vitamins K, optimize nutrition, don’t use low protein diet if encephalopathy Dialy weight, bloods, steroids possible.
- Relapse – Acamprosate at help intense anxiety, insomnia, craving. Disulfiram ca be used for dependance as acetaldehyde build up which is unpleasant with alcohol like flushing etc.
WHat is diabetes mellitus and the consequences
DM = lack of or reduced effectiveness of endogenous insulin. Hyperglyaemia. Causes serious microvascular (retinopathy, nephropathy, neuropathy) or macrovascular problems (Stroke, MI, Renovasular disease, limb ischaemia).
Other causes:
- Pancreatitis , surgery to remove pancreas
- Destruction – cystic fibrosis, hemochromatosis + pancreatic cancer
- Endocrine – Cushin’s disease, pheochromocytoma, hyperthyroidism, pregnancy
Compare T1DM.T2DM - epidemiology genetics, cause, presentation, associations and treatment
T2DM management
Hypertension - what is it and the stages
Hypertension = We choose to select a value above which risk is significantly increased and the benefit of treatment is clear cut. Don’t rly on single reading, confirm with 24hr ambulatory BP monitoring or week of home readings. Diagnostic threshold is lower than about 135/85
Choice of hypertension drug
Invesyiagting posisbel malasbroption
MUST
Vitamins and their deficiency syndrome
minerals and their deficiency syndromes
Bowel cancer symptoms
Treatments of IBD
In severe CD what is the treatment
Steroids in IBD treatment
UC VS CD
(iBS might improve when not stressed but iBD never improves)
Blood Compatibility
Plasma compatibility
Intepretatign ABGS
Management with gI haemorrhage
Abdominal pain in relation to area of abdomen
Omprezaole
Randitidine
Ibuprofen
Steorids MOA
Aspirin
Clopidogrel
Warfarin
Metformin
Gliclazide
Ramipril
Amlodipine
Simvastatin
Furosemide
Angiotensin II receptor blockers
Spironolactone
Thyroxine
Abdo Exam
INTERPRETING THE IRON PANEL
Interpreting FBCs
Examine the neck
Intepret basic endocrinology tests
U&E interpretatin and causes
Basic exam of fluid status
