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67 Cards in this Set
- Front
- Back
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Causes of cirrhosis of the liver x6 (inc. 1 general) |
Alcoholism Chronic hepatitis B, C, D Alpha-1-antitrypsin deficiency, haemochromatosis Wilson's disease metabolic diseases |
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Alcoholic liver disease components x3 |
Hepatic steatosis - dyslipidaemia due to local alcohol metabolism, (NADH production) Alcoholic hepatitis - recurrent inflammation prefiguring scar tissue formation Cirrhosis of the liver (most tissue must be affected before decompensation occurs) |
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Histology of cirrhosis |
Kuppfer cell activation - produce inflammatory factors Stellate cell activation - differentiate into fibroblasts Fibroblasts replace type iii reticular collagen with type i collagen |
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Major aetiologies of cirrhosis symptoms (x7) |
Portal hypertension, hypoalbuminuria (ascites, haemorrhage) Increased oestrogen (various signs) Failed bilirubin conjugation (jaundice, gallstones) Loss of folate, B12 Malabsoption Clotting factor depletion (coagulopathy) Failed urea cycle (encephalopathy, fetor hep.) |
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Normal portal venous pressure Portal hypertension pressure |
~9mmHg Hypertension: >10mmHg |
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Porto-systemic anastomoses |
Distal oesophageal azygous s. - left gastric veins Tributaries of left renal vein - lumbar veins Inferior rectal vein - superior rectal vein Recanalised falciform ligament - epigastric veins |
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Symptoms/complications of portal hypertension x3 |
Porto-systemic haemorrhage Splenomegaly Left renal ischemia 2' to splenomegaly |
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Non-alcoholic causes of portal hypertension |
Stenosis and venous thrombosis May be pre- or post-hepatic |
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Liver cirrhosis treatment x5 |
Potassium-sparing diuretics Anti-angiotensin drugs alcohol cessation/infection treatment Pabrinex (vitamins C, B1, B2, B3, B6) Transplant |
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Pathophysiology of renal problems in cirrhosis |
Cirrhosis causes portal hypertension and increased blood volume in portal system This reduces effective arterial blood volume Loss of renal perfusion triggers RAAS High aldosterone levels causes hypokalaemia, ascites |
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Liver disease presentation x6 disease processes and symptoms |
Increased oestrogen: spider naevi, gynaecomastia, loss of body hair etc. P-S hypertension: haemorrhage, ascites, peripheral oedema, fetor hepaticus (due to shunting of compounds to lung) Hyperbilirubinaemia: jaundice, pigment gallstones Coagulopathy Hepatic encephalopathy due to neuro effect of unexcreted ammonia Macrocytic (haematinic) anaemia due to loss of hepatic vitamin stores. |
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Coeliac pathophysiology |
Gliadin is not hydrolysed by chymotrypsin Gliadin absorbed by enterocyte Gliadin crosslinked with tissue transglutaminase and presented on enterocyte surface Anti-tTG antibodies provoke cell-mediated immune response Enteritis, villous atrophy and malabsorption result |
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Consequences of malabsorption in Coeliac disease (x5) |
Iron-deficient anaemia Steatorrhoea due to loss of fat absorption Coagulopathy due to vitamin K malabsorption Osteomalacia/OP from reduced D/calcium absorption Weight loss due to macronutrient malabsorption |
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Causes of diarrhoea in Coeliac disease (x3) |
High osmotic pressure due to luminal unabsorbed nutrients Bacterial production of hydroxylated fatty acids acts as a cathartic Lactose intolerance due to loss of brush border lactase produces diarrhoea |
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Coeliac presentation (x4) |
Chronic diarrhoea/steatorrhoea/abdominal discomfort Weight loss, lethargy, fatigue Anaemia symptoms Failure to thrive |
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Diagnosis of Coeliac disease x2 |
Serum antibodies against tissue transglutaminase and endomysium Biopsy evidence of villous atrophy, hyperplastic crypts, lymphocytosis |
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T1D antibodies |
Islet cell autoantibodies Insulin autoantibodies Glutamate decarboxylase autoantibodies |
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Blood values in compensated respiratory acidosis |
pH <7.35 pCO2 >45mmHg HCO3>28mM/L |
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Blood values in compensated metabolic acidosis |
pH <7.35 HCO3 <22mM/L pCO2 <35mmHg |
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Blood values in compensated respiratory alkalosis |
pH >7.45 PCO2 <35mmHg HCO3 <22mM/L |
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Blood values in compensated |
pH >7.45 HCO3 >28mM/L pCO2 >45mmHg |
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Pathophysiology of DKA |
Insufficient insulin reduces glucose uptake, increases gluconeogenesis, lipolysis etc. Gluconeugenesis depletes oxaloacetate Increased ketogenesis reduces pH |
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Metabolic acidosis presentation x6 |
Drowsiness/loss of consciousness/coma Seizures/weakness Diarrhoea, nausea, vomiting Tachycardia/arrhythmia SOB Hypothermia |
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Complications of metabolic acidosis x4 |
Cerebral oedema Fluid/electrolyte imbalance due to osmotic diuresis If diabetic cause, insulin replacement -> hypokalaemia due to movement into cells Loss of renal function due to polyuria (exacerbating acid-base disturbance) |
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Anion gap diagnostic use |
Increased unmeasured anions in increased acid production (eg. DKA) Normal anion gap in bicarbonate excretion (due to chloride retention) |
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Effects of hyperprolactinaemia x3 |
Cessation of the menstrual cycle Galactorrhoea Gynaecomastia |
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Sequence of pituitary hormones lost in compression by space-filling tumour |
GH LH/FSH ACTH TSH |
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Diagnostic use of bromocriptine in hyperprolactinaemia |
Bromocriptine is a dopamine agonist. With a patent H-P portal system it will suppress prolactin secretion due to dopamine inhibition, but will have no effect in space-filling disruption of the infundibular stalk |
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Non-endocrine mass effects of pituitary tumour |
Visual field defects consistent with optic chiasm compression: mono- or bi-temporal hemianopia or quadrantanopia. Headache Rarely, opthalmoplegia, optic atrophy, and apoplexy. |
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Effects of panhypopituitarism By hormone system (x4) |
Loss of cortisol produces hypotension and hypoglycaemia Loss of T3 produces lethargy/weakness, loss of exercise capacity, myxoedema Loss of FSH/LH produces loss of libido and secondary sexual characteristics (including menstruation) Acute adrenal insufficiency may be life-threatening due to its effect on electrolyte and fluid balance. |
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Treatment of panhypopituitarism |
Surgery to counter mass effects of tumour Hormone replacement, with target organ hormones (not peptides, so can be administered orally). |
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Cushing's syndrome signs (x4) complications x2 |
'Moon face' Dorsal fat pad Truncal obesity with appendicular wasting Hypertension Osteoporosis DM risk |
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Congenital adrenal hyperplasia effects (x4) |
Symptoms of mineralocorticoid and glucocorticoid deficiency Virilisation of secondary sexual characteristics Failure to thrive Adrenal hypertrophy |
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Major effects of hypoadrenal crisis (x3) +most common cause |
Hypotension Hypoglycaemia Dehydration Abrupt steroid therapy discontinuation (ACTH suppression prevents synthesis of endogenous steroid hormones) |
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Effect of mineralocorticoid-secreting adrenal tumours (x3) |
HT with hypervolaemia hypokalaemia metabolic alkalosis |
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Addison's disease cause Signs Complications w/5 symptoms |
Runaway ACTH secretion due to primary adrenal insufficiency (by AI, infection etc.) Produces characteristic pigmentation of skin, nails, palmar creases, gums May lead to addisonian crisis, with hypotension, hypoglycaemia, V&D, ion derangement, convulsions |
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Cushing's disease Cushing's syndrome + common cause |
Secondary (pituitary, eg. adenoma) or tertiary (hypothalamic) hypercortisolism Cushing's syndrome - manifestations of hypercortisolism. Usually caused by corticosteroid administration |
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Cause of diabetes insipidus |
Loss of hypothalamic-posterior pituitary vasopressin production |
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Presentation of hypoglycaemia (x3) |
Blurred vision and dizziness Confusion and inability to concentrate Pallor, sweating, tremor and palpitations (due to increased sympathetic activity) |
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Causes of hypoglycaemia (x5) |
ETOH inhibition of gluconeogenesis Recurrent severe hypoglycaemia in long-term T1D, including eg. mismatch between diet and insulin administration in T1D Insulinoma Reactive hypoglycaemia - due to increased post-prandial insulin secretion in pre-diabetes Excessive exercise |
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Chronic hypercalcaemia effects x4 |
Renal stones Constipation Dehydration Kidney damage |
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Acute effects of hypocalcaemia x4 |
Paraesthesia Tetany Paralysis Convulsions |
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General manifestations of hypothyroidism (x6) |
Dermatological (myxoedema, hair loss etc.) GI/metabolic (loss of appetite, weight gain) Neurological (depression, loss of concentration) CV (bradycardia, pallor, cold sensitivity) Renal/haemo (Fluid retention, anaemia) Sexual/developmental (reduced fertility, retardation) |
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AI hypothyroidism Name Antibody targets x3 |
Hashimoto's disease Thyroperoxidase, thyroglobulin, TSH receptors etc. |
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Treatment of hypothyroidism |
PO levothyroxine (synthetic T4) |
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Dexamethasone suppression test +interpretation |
Dexamethasone is a corticosteroid which suppresses pituitary ACTH secretion ACTH low, cortisol remains high -> primary hypercortisolism ACTH and cortisol remain high -> ectopic ACTH syndrome ACTH normal/high, cortisol suppressed -> 2'/3' hypercortisolism (Cushing's disease) |
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Metabolic syndrome criteria x5 |
3 or more of BMI>30 or increased waist circumference Hyperlipidaemia Low HDL Blood pressure >130/85 or treatment for HT Fasting blood glucose >5.6mmol/L |
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T2D risk factors x4 +medical history risk factors x5 |
~25% heritability Obesity (BMI>30 RR=40) Age Ethnicity (higher in South Asians, Afro-Caribbeans) CVD, polycystic ovary syndrome, gestational diabetes, HBW babies, mental illness |
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Genes implicated in T2D function x3 |
GKRP (glucokinase regulatory protein) - regulation of glucokinase, the enzyme responsible for hepatic phosphorylation of glucose to G-6-P. Loss of function leads to reduced glycogenesis, hyperglycaemia PPARG - involved in the expression of proteins which stimulate lipid uptake and lipogenesis by adipose cells, therefore increasing glucose utilisation systemically. TCF7L2 - loss of function leads to impaired insulin secretion |
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Development of insulin-resistance |
Toxic metabolites of TAGs taken up by peripheral cells but surplus to requirements for oxidative metabolism disrupt insulin-GLUT interaction Inflammation mediated by cytokines released by macrophages upon adipose tissue infiltration Hyperinsulinaemia, produced in response to low-level insulin-resistance exacerbates that resistance. |
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Diabetes progression according to - insulin levels - insulin action - glucose level |
Insulin rises, falls Insulin action declines B cell insufficiency as glucose progressively rises |
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Basic relationship between increased adiposity and T2D development |
Increased adiposity increases insulin demand Beta cell proliferation; hyperinsulinaemia Insulin resistance develops IoLs degenerate; B-cells undergo apoptosis Chronic hyperglycaemia |
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T2D drug classes x4 + example + action |
Biguanides eg. metformin - activate AMPK, inhibit gluconeogenesis Sulfonylureas eg. gliclazide - activate B cells by blocking potassium channel DPP-4 inhibitors eg. sitagliptin - pro-insulin and insulin-like effects by increasing incretin levels TZDs eg. pioglitazone - activates PPARG to increase fatty acid use in lipogenesis and increase glucose use |
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Non-T1D or T-2D diabetes classesx3 |
Gestational diabetes - due to failure of beta cell compensation for tissue gain Maturity onset diabetes of the young - Dominant inherited beta-cell defects Latent autoimmune diabetes of adults - Accelerated T2D development with AI involvement |
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Diabetes diagnostic tests x3 with caveats |
Plasma glucose levels (2 fasting, or 1 high with symptoms) Oral glucose tolerance test HBA1C readingsAlthough erythrolytic disorders depress readings |
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Normal glycaemic levels |
4-6 mmol/L pre-prandial <7.8mmol/L post-prandial 20-41mmol/L HBA1C |
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Presenting symptoms of diabetes x7 |
Thirst Polyuria Glycosuria Recurrent infection Weight loss Drowsiness Coma |
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Complications of chronic hyperglycaemiax5 |
Atherosclerosis, due to advanced glycation endproducts (impair LPRs, induce inflammation) Dyslipidaemia Microvascular damage involving the polyol pathway, leading to: Retinopathy Neuropathy Nephropathy |
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Polyol pathway in microvascular complications of diabetes |
Nervous, retinal, and renal tissue is not insulin-gated Glucose builds up within cells in hyperglycaemia High levels lead to conversion to sorbitol by aldose reductase High sorbitol cannot be transported out, leading to osmotic stress High sorbitol also causes oxidative stress and ion pump dysfunction |
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When to initiate insulin in T2D |
When glycaemic targets are not being met despite maximal levels or oral glucose-lowering agents |
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Non-alcoholic fatty liver disease definition |
Accumulation of triacylglycerides and other lipids within hepatocytes |
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NAFLD presentation x3 symptoms |
Persistent fatigue/malaise Right upper quadrant pain Hepatomegaly (often asymptomatic) |
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NAFLD diagnosis x3 tests |
LFTs: may be normal, or raised ALT/AST USS Definitive test with biopsy (largely based on risk factors and exclusion - very common) |
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NAFLD complications |
NAFLD can lead to non-alcoholic steatohepatitis, and from there to cirrhosis and hepatocellular carcinoma (as with alcoholic steatosis). |
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NAFLD treatment |
Treatment with lifestyle change, and management of associated diabetes. Abstinence from alcohol recommended. |
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Acanthosis nigrans in hyperinsulinaemia |
Hyperplasia of keratinocytes in the skin due to activation of IGF-1 receptors by insulin. This produces brown/black, poorly defined, velvety pigmentation. |
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Features of diabetic capillaries x4 |
Vasoconstriction Basement membrane thickening Endothelial hyperplasia Vessel wall weakens |
