Metabolism 2 Wk3,4+5 Flashcards
what is normal blood pH range?
- arterial
- venous
What buffer system maintains blood pH?
The normal arterial blood pH range is 7.35 to 7.45. Values below 7.35 indicate acidosis, while those above 7.45 indicate alkalosis.
The normal venous blood pH range is approximately 7.31 to 7.41, which is typically about 0.03 units lower than arterial pH.
What buffer system maintains blood pH?
🧪 Primary Buffer: Bicarbonate Buffer System
🔹 How It Works:
CO₂ + H₂O forms H₂CO₃ (carbonic acid).
H₂CO₃ dissociates into HCO₃⁻ (bicarbonate) and H⁺.
Maintains blood pH (7.35-7.45) by neutralizing excess acids/bases.
⚖ Regulation:
Lungs: Control CO₂ levels (rapid response).
Kidneys: Adjust HCO₃⁻ excretion/reabsorption (slow response).
💡 Key Role: Prevents dangerous pH shifts, ensuring acid-base balance.
What is the main intracellular buffer in the body?
Phosphate Buffer System: Within cells, the phosphate buffer system plays a significant role in regulating pH
What is the main extracellular buffer in the body?
Bicarbonate Buffer System: The primary extracellular buffer, consisting of carbonic acid (H₂CO₃) and bicarbonate ions (HCO₃⁻), helps maintain blood pH within the narrow range necessary for normal enzymatic activity
methanol is metabolised into what dangerous compound and what kind of acidosis does it cause?
Methanol → Formaldehyde → Formic Acid (via alcohol dehydrogenase & aldehyde dehydrogenase)
Formic acid accumulation leads to metabolic acidosis with a high anion gap and increased osmolal gap.
n.b. ethylene glycol (antifreeze) is metabolised into glycolic acid, oxalic acid, glycoxylic acid and causes metabolic acidosis
How does carbon monoxide poisoning lead to metabolic acidosis
1) CO Binding to Hemoglobin:
CO binds to hemoglobin, forming carboxyhemoglobin (COHb), reducing oxygen transport.
2) Tissue Hypoxia:
Oxygen deprivation forces cells to switch to anaerobic metabolism.
3) Lactic Acid Production:
Anaerobic metabolism generates lactic acid, which accumulates in the blood.
4) Metabolic Acidosis:
Excess lactic acid lowers blood pH, overwhelming buffering systems.
5) Systemic Effects:
Acidosis impairs organ function, causing symptoms like confusion, arrhythmias, or coma.
What is the pathophysiology of diabetic ketoacidosis (DKA), and how do acetoacetate and beta-hydroxybutyrate contribute to acidosis?
1) Insulin Deficiency:
Lack of insulin prevents glucose uptake, causing hyperglycemia.
2) Counterregulatory Hormones:
Glucagon, cortisol, and epinephrine increase gluconeogenesis and glycogenolysis, worsening hyperglycemia.
3) Lipolysis and Ketogenesis:
Fat breaks down into free fatty acids, which are converted into ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) in the liver.
4) Ketone Body Accumulation:
Beta-hydroxybutyrate (predominant) and acetoacetate are acidic and accumulate in the blood.
5) Metabolic Acidosis:
- Ketone bodies release hydrogen ions (H⁺), lowering blood pH.
- Bicarbonate buffering is overwhelmed, leading to acidosis.
6) Systemic Effects:
- Kussmaul respirations (deep, rapid breathing to compensate).
- Altered mental status (confusion, lethargy, coma).
- Electrolyte imbalances and dehydration due to osmotic diuresis.
Treatment:
- IV fluids for dehydration.
- Insulin therapy to suppress ketogenesis.
- Electrolyte replacement (e.g., potassium).
- Bicarbonate (only if pH < 6.9! never if above can cause paradoxical intracellular acidosis, hypokalemia, delayed ketone clearance, and alkalosis)
What ketones are key in DKA
Key Ketone Bodies:
Acetoacetate: Detected in urine ketone strips.
Beta-Hydroxybutyrate: Predominant in DKA, highly acidic.
Acetone: Excreted via lungs, causes fruity breath odor.
How do the kidneys handle bicarbonate to maintain acid-base balance?
- Bicarbonate Filtration:
- Freely filtered at the glomerulus - Bicarbonate Reabsorption:
~80–90% reabsorbed in the proximal tubule.
10–20% reabsorbed in the thick ascending limb and distal tubule.
Mechanism:
- H⁺ secreted into lumen via Na⁺/H⁺ exchangers (NHE3) and H⁺-ATPase.
- H⁺ combines with filtered HCO₃⁻ to form H₂CO₃, which breaks down into CO₂ + H₂O (catalyzed by carbonic anhydrase).
- CO₂ diffuses into cells, regenerates HCO₃⁻, which is transported into blood.
- Generation of New Bicarbonate:
Occurs in collecting ducts to replace HCO₃⁻ lost in buffering acids.
Mechanisms :
Phosphate Buffer System:
H⁺ binds to HPO₄²⁻ → excreted as H₂PO₄⁻.
= Generates new HCO₃⁻.
Ammonia Buffer System:
NH₃ (from glutamine) binds to H⁺ → excreted as NH₄⁺.
= Generates new HCO₃⁻.
- Regulation:
Acidosis: Increases H⁺ secretion and HCO₃⁻ reabsorption/generation.
Alkalosis: Decreases H⁺ secretion and HCO₃⁻ reabsorption/generation.
Key Regulators:
- Angiotensin II: Stimulates Na⁺/H⁺ exchange in proximal tubule.
- Aldosterone: Increases H⁺ secretion in collecting ducts.
- PCO₂: High CO₂ increases HCO₃⁻ reabsorption; low CO₂ decreases it.
Summary:
Reabsorb filtered HCO₃⁻ and generate new HCO₃⁻ to maintain acid-base balance.
Tightly regulated by hormones and acid-base status.
Non-volatile acids (e.g., sulfuric acid from sulfur-containing amino acids, phosphoric acid from phospholipids/nucleic acids) are buffered by the kidneys using HCO₃⁻. The kidneys excrete H⁺ and regenerate HCO₃⁻. What buffer system is used in acute acidosis vs chronic acidosis
In acute acidosis (e.g., lactic acidosis after exercise), the bicarbonate buffer system is the first line of defense to neutralize H⁺.
Once bicarbonate is depleted, the body uses phosphate and ammonia buffers to excrete H⁺ and regenerate HCO₃⁻.
In chronic acidosis (e.g., chronic metabolic acidosis), the ammonia buffer system becomes the primary mechanism because it can adapt and handle large, sustained acid loads by excreting H⁺ as NH₄⁺ and generating new HCO₃⁻.
Summary:
Acute acidosis: Bicarbonate → phosphate → ammonia.
Chronic acidosis: Ammonia is the main buffer.
what is hyperchloremia
Hyperchloremia is an electrolyte disturbance in which there is an elevated level of chloride ions in the blood. The normal serum range for chloride is 96 to 106 mEq/L, therefore chloride levels at or above 110 mEq/L usually indicate kidney dysfunction as it is a regulator of chloride concentration
Hyperchloremia (high chloride) often occurs in non-anion gap metabolic acidosis, where the primary issue is a loss of bicarbonate (HCO₃⁻) or an increase in chloride.
Where is the pituitary gland (aka hypophysis) located?
pituitary gland (aka hypophysis) = a pea-sized endocrine gland located centrally in the base of the brain, lying in a depression of the sphenoid bone called sella turcica (‘turkish saddle’)
What is Renal Tubular Acidosis (RTA)?
A group of disorders where the kidneys cannot properly acidify urine, leading to metabolic acidosis despite normal or only mildly reduced kidney function.
Key Features:
- Metabolic acidosis with a normal anion gap.
- Hyperchloremia (elevated chloride levels).
Urine pH is inappropriately high (>5.5) in distal RTA. N.b. Norm urine pH is 5 to 7, depending on diet.
Clinical Symptoms:
Fatigue, muscle weakness, bone pain, kidney stones (distal RTA), or growth failure in children.
Treatment:
Alkali therapy (e.g., sodium bicarbonate or potassium citrate) to correct acidosis and prevent complications.
Type 1 (Distal RTA):
- Defect in the distal tubule’s ability to secrete H⁺.
- Causes: Genetic, autoimmune, or drug-induced.
Type 2 (Proximal RTA):
- Defect in the proximal tubule’s ability to reabsorb HCO₃⁻.
- Causes: Fanconi syndrome, multiple myeloma, or toxins.
Type 4 (Hyperkalemic RTA):
- Caused by aldosterone deficiency or resistance, leading to impaired H⁺ and K⁺ excretion.
- Causes: Diabetes, kidney disease, or medications (e.g., ACE inhibitors, NSAIDs).
What is the driving force for patients with COPD to keep breathing? What is the target o2 saturation in a normal person vs someone with COPD
In patients with COPD the driving force to keep breathing is hypoxia (low o2 levels)?
Target o2 saturation in norm person 94%+
TARGET SATURATION IN COPD= 88-92%
define the following
- febrile
- moribund
febrile= look like have fever
moribund= look like you’re about to die
What connects the pituitary gland to the hypothalamus?
connected by a short stalk called the infundibulum (this stalk contains the vascular network connecting pituitary + hypothalamus)
What type of tissue is the pituitary glands
- anterior lobe (adenohypophysis) made up of?
- posterior lobe (neurohypophysis) made up of?
anterior lobe (adenohypophysis) is made up of glandular epithelial tissue
posterior lobe (neurohypophysis) is made out of neural secretory tissue
There are 5 types of hormone producing cell in the anterior pituitary, they are listed below. Name the hormones produced by each; then tell me whether they are acidophils (stain with acid stain) , basophils (stain with basic dyes) or chromophobes (don’t stain)
- Somatotrophs
- Lactotrophs
- Corticotrophs
- Thyrotrophs
- Gonadotrophs
Somatotrophs (acidophil) : Growth Hormone (GH) = Stimulates growth and repair (research ongoing for adult functions).
Lactotrophs (acidophil): Prolactin = Stimulates milk production in breasts (present in both men and women).
Corticotrophs (basophils stain with PAS):
- Adrenocorticotropic Hormone (ACTH) = Stimulates adrenal gland to produce cortisol.
- Melanocyte Stimulating Hormone (MSH) = Exact role not fully understood.
- Pro-opiomelanocortin (POMC) = Precursor to ACTH and MSH
Thyrotrophs (basophils stain with PAS): Thyroid Stimulating Hormone (TSH) = Stimulates thyroid gland to secrete thyroxine.
Gonadotrophs (basophils stain with PAS):
- Follicle Stimulating Hormone (FSH) = Stimulates development of ovarian follicles and promotes oestrogen production by the granulosa cells of the follicles. In men, stimulates the Sertoli cells in the testes to support spermatogenesis
- Luteinizing Hormone (LH) = Triggers ovulation (the release of a mature egg from the ovary). Stimulates the corpus luteum to produce progesterone after ovulation. In men, stimulates Leydig cells to produce testosterone
what is the PAS stain used for?
The PAS stain (Periodic Acid-Schiff stain) is a special staining technique used in histology to detect certain structures in tissues, particularly carbohydrates like glycogen, glycoproteins, and glycolipids. In the context of the anterior pituitary, PAS staining is particularly useful for identifying basophils, which are cells that produce certain hormones.
The posterior lobe of the pituitary gland (neurohypophysis) is an extension of the CNS, as it stores and releases secretory products from the hypothalamus. Neurohypophysis is NOT an endocrine gland. What does the posterior lobe do?
The posterior lobe contains neuroendocrine secretory granules (carrier protein is neurophysin) and is not a true endocrine gland because it does not synthesize hormones itself. Instead, it stores and releases:
- Oxytocin (Stimulates uterine contractions during childbirth. Promotes milk ejection (let-down reflex) during breastfeeding.
Role in social bonding and emotional regulation.) - Vasopressin (Antidiuretic Hormone, ADH)= Regulates water balance by increasing water reabsorption in the kidneys, reducing urine output (+ constricts blood vessels; increase BP)
what are the glial cells (astrocyte-like cells) found in the posterior pituitary gland called, and what glial fibrillary acidic protein do they contain?
PITUICYTES (glial cells), astrocyte-like cells branched with nuclei (contain glial fibrillary acidic protein GFAP + have supporting role)
The parathyroids have 2 main cell types, what are these and how do they stain
Chief Cells:
(aka principal cells)= these are amphophillic (stain with both acid and basic dyes) these produce PARATHYROID HORMONE (stain with Cytokeratin, Chromogranin, and Parathyroid hormone)
- Stain lightly with H&E (pale or clear cytoplasm).
- They are the primary source of PTH.
Oxyphil Cells (oncocytic cells= pink):
- Stain darkly with eosin (pink, granular cytoplasm due to abundant mitochondria).
- Their function unknown
What does “oncocytic” mean? Where are oncocytic cells commonly found? How do oncocytic cells stain? What is the clinical significance of oncocytic cells?
What does “oncocytic” mean?
- Refers to cells with abundant mitochondria, giving them a granular, eosinophilic (pink) appearance under a microscope.
- These cells are larger and have a densely packed, granular cytoplasm.
Where are oncocytic cells commonly found?
- Parathyroid gland: Oxyphil cells.
- Thyroid gland: Hürthle cell tumors.
- Salivary glands: Oncocytomas.
- Kidneys: Renal oncocytomas.
- Other tissues: Pituitary, adrenal glands,
How do oncocytic cells stain?
- Stain darkly with eosin (pink) in H&E staining due to high mitochondrial content.
- May also stain with PTAH or mitochondrial-specific stains.
What is the clinical significance of oncocytic cells?
- Can be benign (e.g., oncocytomas) or malignant (e.g., oncocytic carcinomas).
- Often associated with aging and may represent a response to cellular stress or metabolic changes
What is inside the colloid of thyroid follicles?
Iodinated Thyroglobulin= A glycoprotein that stores inactive thyroid hormones (its what makes up the gel-like colloid of the thyroid follicles)
Inactive T4 (thyroxine) and a small amount of T3 (triiodothyronine).
How are thyroid hormones activated and released?
Iodine is added to thyroglobulin in the colloid, forming T4 and T3.
Follicular cells reabsorb thyroglobulin and break it down.
Free T4 and T3 are released into the bloodstream.
Where are parafollicular cells (C cells) located and what hormone do they produce?
The parafollicular cells (aka clear cells, C cells) are located in the thyroid gland (Between thyroid follicles, they’re scattered among follicular cells (but NOT in the colloid).
C cells/ parafollicular make + secrete calcitonin; a hormone that lowers blood calcium levels by:
- Inhibiting bone resorption.
- Promoting calcium excretion by the kidneys.
What is the primary function of Parathyroid Hormone (PTH)? How does PTH affect bone tissue?
Regulates calcium and phosphate levels in the blood by acting on bones, kidneys, and intestines
Stimulates bone resorption by activating osteoclasts, releasing calcium and phosphate into the bloodstream.
What are the effects of PTH on the kidneys? How does PTH indirectly increase calcium absorption in the intestines?
effects of PTH on the kidneys:
- Increases calcium reabsorption in the distal tubules.
- Decreases phosphate reabsorption in the proximal tubules.
- Activates vitamin D (converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D).
What happens if PTH levels are too high (hyperparathyroidism)? What happens if PTH levels are too low (hypoparathyroidism)?
hyperparathyroidism; Leads to hypercalcemia (high blood calcium), bone weakening, and kidney stones due to excessive bone resorption and calcium reabsorption.
hypoparathyroidism= Leads to hypocalcemia (low blood calcium), muscle cramps, and tetany due to insufficient calcium release from bones and reduced calcium reabsorption.
Hashimoto’s thyroiditis damages the follicular cells, what name is given to these damaged follicular cells?
Hürthle cells
characteristics:
- Abundant eosinophilic cytoplasm (due to increased mitochondria).
- Enlarged, granular appearance under a microscope.
Why do Hürthle cells form in Hashimoto’s thyroiditis? As a response to chronic inflammation and damage to follicular cells caused by autoimmune attack.
The adrenal (suprarenal) glands have a steroid secreting portion and a catecholamine secreting portion. Which is which?
cortex= steroid secreting portion
medulla (chromaffin cells) = catecholamine secreting portion
the cortex of the adrenal glands has 3 zones; what are the major hormones produced in each?
- zona glomerulosa
- zona fasciculata
- zona reticularis
zona glomerulosa= mineralocorticoids (e.g. Aldosterone)
zona fasciculata= glucocorticoids (e.g. Cortisol)
zona reticularis= androgenic steroids (e.g. Androgens e.g., DHEA, androstenedione)
What is the difference between Cushing’s disease and Cushing’s syndrome?
Cushing’s syndrome: Any condition with excessive cortisol levels (exogenous or endogenous causes).
Cushing’s disease: A specific cause of Cushing’s syndrome due to a pituitary adenoma secreting excess ACTH.
What are the physical symptoms of Cushing’s syndrome?
Weight gain (central obesity, moon face, buffalo hump).
Skin changes (thin skin, purple striae, easy bruising).
Muscle weakness (proximal muscle weakness).
Hirsutism (excessive hair growth in women).
What are the metabolic symptoms of Cushing’s syndrome?
Hyperglycemia (high blood sugar).
Hypertension (high blood pressure).
Dyslipidemia (abnormal lipid levels).
What are the bone-related symptoms of Cushing’s syndrome?
Osteoporosis (weak, brittle bones).
Growth retardation (in children).
What hormone do the following cells of the pancreas produce and what is the function
- beta cells/ β-cells
- alpha cells/ α-cells
- delta cells / δ-cells
- Pancreatic Polypeptide Cells/ PP cells
beta cells/ β-cells; INSULIN ;Lowers blood glucose levels by:
- Promoting glucose uptake by cells (especially muscle and fat cells).
- Stimulating glycogen synthesis in the liver.
- Inhibiting gluconeogenesis (glucose production by the liver).
alpha cells/ α-cells; GLUCAGON; Raises blood glucose levels by:
- Stimulating glycogen breakdown (glycogenolysis) in the liver.
- Promoting gluconeogenesis (glucose production by the liver).
delta cells / δ-cells; SOMATOSTATIN; paracrine inhibitor; suppresses both insulin + glucagon release; decreases GI motility. Somatostatin stops insulin release when you have low blood glucose to prevent your levels from dropping further
Pancreatic Polypeptide Cells/ PP cells; PANCREATIC POLYPEPTIDE; Regulates pancreatic secretion + GI function
What is the role of secretion in renal excretory function?
Waste products and excess ions are actively secreted from the blood into the tubular fluid.
How is final urine formed and excreted?
Final urine is formed in the collecting ducts by adjusting water reabsorption (via ADH) and excreted from the body.
What are the key steps in renal excretory function? Below is lay summary; give the detail;
1) Filtration: Blood is filtered in the glomerulus to form filtrate.
2) Reabsorption: Essential substances are reabsorbed in the tubules.
3) Secretion: Waste products and excess ions are secreted into the tubules.
4) Excretion: Final urine is formed and excreted.
1) Filtration @ Glomerulus:
- Blood enters via afferent arteriole, exits via efferent arteriole.
- High pressure forces water, ions, small molecules into Bowman’s capsule.
- Large molecules (e.g., proteins) retained.
Reabsorption @ Renal Tubules:
- PCT: Reabsorbs glucose, amino acids, ions (Na⁺, K⁺, Cl⁻).
- Loop of Henle: Establishes osmotic gradient; descending limb (water permeable), ascending limb (ion transport).
- DCT: Fine-tunes reabsorption (e.g., aldosterone regulates Na⁺, K⁺).
Secretion @ Renal Tubules:
- PCT & DCT: Secretes waste (urea, creatinine), drugs, toxins.
- Regulates acid-base balance (H⁺ secretion, HCO₃⁻ reabsorption).
Excretion @ Collecting Ducts:
- Adjusts water reabsorption via ADH.
- Excretes excess water, waste, ions as urine.
Regulation:
Tubuloglomerular Feedback: Macula densa senses NaCl, regulates GFR.
RAAS: Renin release → angiotensin II → aldosterone → Na⁺ reabsorption, blood pressure regulation.
Autoregulation: Maintains constant GFR via myogenic response, tubuloglomerular feedback.
What is the difference between osmolality and osmolarity?
Osmolality: Osmoles of solute per kilogram of solvent (Osm/kg); independent of temperature/pressure.
Osmolarity: Osmoles of solute per liter of solution (Osm/L); depends on temperature/pressure.
Clinical Use: Osmolality is preferred for biological fluids.
What is the role of the macula densa?
The macula densa= specialised region of the distal convoluted tubule (DCT) that lies adjacent to the juxtaglomerular apparatus (JGA).
Function:
- Senses NaCl levels in tubular fluid.
- Regulates Glomerular Filtration Rate (GFR):
If NaCl levels are too high, the macula densa signals the afferent arteriole to constrict, reducing GFR (tubuloglomerular feedback). - Stimulates Renin Release:
Low NaCl levels triggers renin release from juxtaglomerular cells, activating the renin-angiotensin-aldosterone system (RAAS) to increase blood pressure and sodium reabsorption.
What is the podocyte slit diaphragm?
podocyte slit diaphragm= a thin, zipper-like structure between podocyte foot processes in the glomerulus.
- Acts as the final layer of the glomerular filtration barrier, preventing protein loss while allowing water and small molecules to pass.
function of podocyte slit diaphragm;
- Filtration barrier: Prevents passage of large molecules (e.g., proteins).
- Selective permeability: Allows passage of water and small molecules.
- Structural support: Maintains glomerular integrity.
What is the role of aquaporins?
Aquaporins are water channel proteins found in the cell membranes of renal tubules (especially the proximal tubule and collecting duct).
- Facilitate water reabsorption in renal tubules.
- AQP2 (regulated by ADH) increases water reabsorption in the collecting duct.
- Help maintain fluid balance and urine concentration.
What happens if the podocyte slit diaphragm is damaged?
Leads to proteinuria and kidney diseases like nephrotic syndrome (podocyte slit diaphragm damage= lose oncotic pressure= OEDEMA + proteinuria
What is nephrotic syndrome, and what are its key features, causes, and treatments?
Definition: A kidney disorder with heavy proteinuria (≥3.5 g/day), hypoalbuminemia (<3 g/dL), edema, and hyperlipidemia.
Causes:
1) Primary: Minimal change disease, FSGS, membranous nephropathy.
2) Secondary: Diabetes, lupus, infections, amyloidosis.
Features: Edema, foamy urine, fatigue, infection risk, thromboembolism.
Treatment: Corticosteroids, immunosuppressants, ACE inhibitors/ARBs, diuretics, statins.
Indapamide
Indapamide is a thiazide-like diuretic. It inhibits the activity of the sodium-chloride symporter in the distal convoluted tubule, preventing reabsorption of these ions from the tubular lumen. This results in increased urine osmolality, which draws more water into the lumen, resulting in increased diuresis. Side effects of this drug include hyponatraemia, hypokalaemia, hypercalcaemia (which may potentiate gout development), and hypercholesterolemia.
Indapamide has no effect on the proximal convoluted tubule (PCT)
What enzyme does parathyroid hormone (PTH) stimulate to convert 25-hydroxy vitamin D
Parathyroid hormone (PTH) stimulates the enzyme 1-alpha hydroxylase, which converts 25-hydroxy vitamin D (calcifediol) to the biologically active form of vitamin D known as 1,25-dihydroxy vitamin D (calcitriol). This reaction takes place in the kidneys. PTH also acts to increase serum calcium through indirect stimulation of osteoclasts, leading to increased bone resorption, which results in the release of calcium from bone stores.
How is creatinine clearance measured?
Clearance= (urine concentration x urine volume)/ plasma concentration
Cr= (Ucr x V)/ Pcr
Ucr= urine Cr concentration
Pcr= plasma Cr concentration
V= volume of urine per minute
What is creatinine + its function?
Creatinine (produced by muscles)
- A waste product from the breakdown of creatine phosphate in muscles.
- Used as a marker of kidney function.
function:
- Marker of kidney function: Elevated levels indicate reduced kidney function.
- Used to estimate GFR: Helps assess how well the kidneys are filtering waste.
- Reflects muscle metabolism: Production is proportional to muscle mass.
What is the NICE gold standard for measuring GFR?
CKD-EPI equation (Chronic Kidney Disease Epidemiology Collaboration equation) is a used to estimate eGFR using serum creatinine, age, sex, and race.
How is CKD-EPI used?
- Measure serum creatinine using a standardized method.
- Input serum creatinine, age, sex, and race into the CKD-EPI formula.
- Interpret eGFR to stage CKD (stages 1-5).
what effect do the following have on GFR
- muscular individuals
- malnourished individuals
- Trimethoprin
- muscular individuals; naturally have raised serum creatinine i.e. eGFR underestimates true GFR (when using calculator when you add more creatinine level the eGFR value gets lower)
- malnourished individuals have low serum creatinine i.e. eGFR overestimates true GFR
- Trimethoprin; drug inhibits tubular secretion of creatinine leading to raised plasma creatinine even tho GFR may be unchanged
Defects in transport proteins leads to renal disease; explain what defects in the following cause:
Proximal tubule;
- Apical Na/ cystine cotransporter
- Apical Na/glucose cotransporter (renal glycosuria)
- Basolateral Na/HCO3 cotransporter
Thick ascending loop of henle;
- Apical Na/K/2Cl co transporter (aka NKCC2)
Distal tubule:
- Apical Na-Cl contransporter
Proximal tubule;
- Apical Na/ cystine cotransporter (Cystinuria; is an inherited autosomal recessive disease characterized by high concentrations of the amino acid cystine causes stones to form in the kidney, ureter, or bladder)
- Apical Na/glucose cotransporter (renal glycosuria)
- Basolateral Na/HCO3 cotransporter (Proximal Renal Tubular Acidosis/RTA)
Thick ascending loop of henle;
- Apical Na/K/2Cl co transporter (Bartter type 1; Caused by mutations in the SLC12A1 gene, which encodes NKCC2
Distal tubule:
- Apical Na-Cl contransporter (Gitelman’s; characterized by defective salt reabsorption in DCT; caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter (NCC)
what is renal threshold?
renal threshold is the concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine
renal thresholds vary by substance e.g. urea is removed at much lower concs than glucose
What are the key steps in the vomiting (emesis) process?
Forceful expulsion of gastric contents:
- Sustained contraction of abdominal muscles.
- Descent of the diaphragm.
- Opening of the lower esophageal sphincter.
- Gastric retropulsion (backward movement of stomach contents).
Defensive mechanisms:
- Larynx closes to prevent aspiration.
- Upper esophageal sphincter opens.
- Crural fibers relax.
- Stomach relaxes.
- Intestinal retropulsion and retrograde giant contractions occur.
what is gastroparesis?
Gastroparesis= stomach empties slowly due to impaired motility, without any physical blockage.
Causes:
- Diabetes (most common cause).
- Post-surgical complications.
- Neurological disorders (e.g., Parkinson’s disease).
- Idiopathic
Symptoms:
Nausea, vomiting, early satiety after eating, bloating, postprandial fullness, belching, abdominal pain, and weight loss.
Treatment:
- Dietary changes: Small, frequent meals; low-fat, low-fiber foods.
- Medications: Prokinetic agents (e.g., metoclopramide), antiemetics.
Severe cases: Gastric electrical stimulation or feeding tubes.
What brain regions are involved in the vomiting reflex?
Area Postrema (AP): Chemoreceptor trigger zone in the medulla.
Nucleus Tractus Solitarius (NTS): Integrates sensory input in the medulla.
Vomiting Center: Coordinates the reflex in the medulla.
Vestibular System: Involved in motion sickness.
Higher Brain Centers (cortex, limbic system): Process emotional and sensory triggers.
stimulating vagus also leads to vomiting
what prevent aspiration when u vomit
larynx closes (to prevent aspiration) when you vomit
Promethazine
First-generation antihistamine and anti-emetic; causes severe drowsiness
Treats insomnia, nausea, vomiting, motion sickness, and allergic reactions.
Blocks H1 histamine receptors, muscarinic acetylcholine receptors and dopamine D2 receptors
n.b. D2 not involved in motion sickness
What are the 1st line interventions for the following
- morning sickness
- motion sickness
- Chemotherapy-Induced Nausea/Vomiting (CINV)
Morning Sickness:
1st-line: Non-pharmacological measures (e.g., ginger, small frequent meals).
1st-line pharmacological if needed: Prochlorperazine or metoclopramide.
2nd-line: Ondansetron{5HT3 antagonist} (if 1st-line fails)
Motion Sickness:
- 1st-line: Promethazine or cyclizine.
Chemotherapy-Induced Nausea/Vomiting (CINV):
- 1st-line: Combination of 5-HT3 antagonists, NK1 antagonists, and dexamethasone (depending on emetogenic risk).
Highly Emetogenic Chemotherapy: Use triple therapy (5-HT3 antagonist + NK1 antagonist + dexamethasone).
Moderately Emetogenic Chemotherapy: Use double therapy (5-HT3 antagonist + dexamethasone).
what is the 1st line (NICE) for Postoperative Nausea and Vomiting (PONV)
Postoperative Nausea and Vomiting (PONV)= use Apfel score to assess risk
Prophylactic Anti-Emetics:
5-HT3 Antagonists:
Ondansetron (4 mg IV).
Dopamine D2 Antagonists:
Droperidol, Prochlorperazine
Dexamethasone (corticosteroid)
Rescue Therapy for PONV;
Cyclizine, Metoclopramide
Mechanism Behind Nausea: Role of Interstitial Cells of Cajal (ICC) and Vagal Pathways
Interstitial Cells of Cajal (ICC):
- Located in different layers of the GI muscle wall and associated with the myenteric plexus.
- Form syncytia (connected groups) and spontaneously depolarize.
- Generate slow waves of electrical activity that propagate from the corpus to the pylorus.
Vagal Nerve Involvement:
- ICCs are closely associated with vagal terminals.
- Vagal pathways transmit signals of mechanical activity to the brain, specifically to the right anterior insula.
Smooth Muscle Contraction:
- ICCs interact with enteric neurons and smooth muscle cells via gap junctions.
- Depolarization opens Ca²⁺ channels, leading to muscle contraction.
Brain Monitoring:
- The brain monitors gastric ICC slow-waves through vagal pathways.
- Disruptions or abnormal activity in these pathways can contribute to the sensation of nausea.
3 Ways Renal Excretory Function is Regulated
Tubuloglomerular Feedback:
- Mechanism: Macula densa cells in DCT sense NaCl levels.
- Response: Adjusts afferent arteriole diameter to regulate GFR.
- Purpose: Maintains stable GFR and efficient filtration.
Renin-Angiotensin-Aldosterone System (RAAS):
- Mechanism: Juxtaglomerular apparatus releases renin in response to low BP, low NaCl, or sympathetic activation.
- Response: Renin → Angiotensin I → Angiotensin II → Aldosterone release.
- Purpose: Increases Na⁺ reabsorption, blood volume, and BP.
Autoregulation:
- Mechanism: Maintains constant GFR via:
- Myogenic Response: Afferent arteriole constricts/dilates with BP changes.
- Tubuloglomerular Feedback: Adjusts GFR based on NaCl levels.
- Purpose: Protects kidneys and ensures consistent filtration.
Define epigenetics then explain the role of epigenetics in obesity via the example of hypomethylation of the Avy gene in mice
Epigenetics= is like a set of switches that turn genes on or off without changing the actual DNA code. These switches can be influenced by things like your environment, diet, and lifestyle. They help control how your genes work and can affect things like your health, how you age, and even your risk for certain diseases. Even though your DNA stays the same, these switches can change and sometimes be passed down to your kids.
Example: Hypomethylation of the Avy Gene in Mice:
- Mechanism: Reduced methylation of the agouti viable yellow (Avy) gene leads to aberrant expression of a protein binding to the melanocortin-4 receptor (MC4R) in the hypothalamus.
- Effect: Disrupts energy homeostasis and appetite regulation, causing hyperphagia (insatiable appetite).
- Intervention: Feeding affected mice (Avy gene mutation) with folate and methionine (methyl donors) improves body weight and insulin resistance.
Epigenetic changes like DNA methylation, significantly impact obesity and can be influenced by dietary factors.
Rare Genetic Forms of Obesity
Mutations in genes like LEP, LEPR, POMC, or MC4R can disrupt appetite regulation, leading to severe obesity.
Treatments may involve hormone replacement (e.g., leptin for leptin-deficient patients) or drugs targeting specific pathways (e.g., MC4R agonists).
MC4R mutation is the most common cause of monogenic obesity
N.B. this type of inherited genetic obesity is MONOGENIC and presents very early in life with fast onset
How Appetite is Regulated
Appetite is regulated by a balance of:
- Hunger signals: AgRP and NPY (promote eating).
- Satiety signals: POMC, α-MSH, and CART (suppress eating).
LEPTIN; long term appetite regulator produced by adipocytes;
- High leptin → Activates POMC/CART, inhibits AgRP/NPY → Reduces appetite.
- Low leptin → Activates AgRP/NPY, inhibits POMC/CART → Increases appetite.
Dysregulation of these pathways (e.g., mutations in POMC, MC4R, or LEPR) can lead to obesity or metabolic disorders.
What are the key components of peripheral and central appetite regulation?
Arcuate Nucleus (ARC): Located in the mediobasal hypothalamus. Contains 2 key neuron types:
- POMC Neurons: Release α-MSH and CART to suppress appetite.
- AgRP Neurons: Release AgRP and NPY to promote hunger.
Leptin: Produced by adipocytes (fat cells). Signals energy sufficiency to brain by:
- Stimulating POMC neurons
- Inhibiting AgRP neurons
Other Key Players:
- BDNF: Regulates energy expenditure via TRKB receptor.
- SIM1: Transcription factor in PVN for appetite regulation.
- VMN: Controls satiety and energy balance
Melanocortin Pathway: Central to appetite regulation:
- α-MSH (from POMC) binds to MC4R to suppress appetite.
- AgRP blocks MC4R, promoting hunger.
- Dysregulation (e.g., mutations in POMC, MC4R, or LEPR) can lead to obesity.
Ghrelin: The “hunger hormone” activates AgRP/NPY neurons, increasing appetite during energy deficiency.
What is the role of
- POMC/CART
- AgRP/NPY
- Leptin
- Ghrelin
Then explain the mechanism behind hunger and fullness
POMC/CART: The “stop eating” signals. They make you feel full.
AgRP/NPY: The “start eating” signals. They make you feel hungry.
Leptin (indicator of fullness) turns on POMC/CART when you have enough energy.
Ghrelin turns on AgRP/NPY when you need energy.
mechanisms:
HUNGER: Ghrelin is released from stomach when it contracts, detected by vagus nerve; projects to ARC. This Ghrelin input from vagus makes u hungry stims AGRP + NPY, inhibits POMC + CART= increased hunger
SATIETY: when food (chyme) in stomach/s.intestine CCK + GLP-1 + PPYY released= these act on ARC= stims POMC + CART= inhibits AGRP + NPY= decreased hunger= increased satiety
What genetic mutation causes leptin deficiency + what are the clinical features
mutation in LEP (located on chromosome 7q31.2 in humans) which encodes the leptin hormone
N.B. Leptin (indicator of fullness) turns on POMC/CART when you have enough energy.
clinical features:
- Hyperphagia (insatiable appetite) and aggression when food is denied
- Abnormalities in T cell number and function, leading to high rates of childhood infections and mortality
- Hyperinsulinemia and Type 2 diabetes in the 3rd to 4th decade
- Secondary hypothyroidism
- Abnormal pubertal development with hypogonadotropic hypogonadism
- Appropriate linear growth in childhood, but reduced final height due to lack of pubertal growth spurt
What does the MC4R gene code for, and why does its mutation cause monogenic obesity?
MC4R Gene Function: The MC4R gene encodes the melanocortin-4 receptor, a protein involved in the regulation of appetite, energy expenditure, and body weight. It is part of the leptin-melanocortin pathway in the hypothalamus.
Mutation Impact: Mutations in the MC4R gene can lead to monogenic obesity by disrupting the receptor’s function. This disruption impairs the signaling pathway that normally suppresses appetite and increases energy expenditure, resulting in excessive hunger, reduced satiety, and increased fat storage. MC4R mutations are the most common cause of monogenic obesity.
What is the NICE guideline for bariatric surgery eligibility
bariatric surgery for those
- BMI ≥40kg/m2 OR
- BMI 35-40lg/m2 + comorbidities
- when all non-surgical measures have failed to achieve clinically beneficial weight loss ≥6 months
- surgery NOT recommended in children/ young ppl
What is GLP-1; what is an incretin hormone?
GLP-1 (Glucagon-Like Peptide-1)= A 31-amino acid peptide; member of the incretin family.
Made by: L-cells in the ileum+ colon (mainly) + brain (nucleus tractus solitarius).
Released: After food intake.
Functions:
- Increases satiety, reduces hunger, promotes weight loss.
- Lowers blood glucose by stimulating insulin secretion.
- Incretin Role: Works with GIP (from K-cells) to enhance insulin release during hyperglycemia.
What are the definitions of anorexigen and orexigen?
Anorexigen: A substance or signal that suppresses appetite and reduces food intake. Examples include leptin and certain hypothalamic neuropeptides like α-MSH (alpha-melanocyte-stimulating hormone).
Orexigen: A substance or signal that stimulates appetite and increases food intake. Examples include ghrelin and neuropeptide Y (NPY).
lauric acid induces the release of ___ hormones from the human colon
lauric acid induces the release of ANORECTIC hormones from the human colon
anorectic= suppresses appetite and reduces food intake
Where is GHRELIN made, released + function
Ghrelin (orexigenic)
Made: fundus + body of stomach
Secreted by: P/D1 cells (a type of enteroendocrine cell) located in the oxyntic (gastric) glands of the stomach.
function: released when stomach empty/ hungry; signals hunger and stimulates appetite (orexigenic)
Where is Cholecystokinin (CCK) made, released + function
Cholecystokinin (CCK)
made: duodenum (small intestine)
secreted by: Enteroendocrine I- cells
function:
- stimulates bile release and pancreatic enzymes.
- promotes satiety (reduces hunger).
- slows gastric emptying.
Where is Peptide YY (PYY) made, released + function
Peptide YY (PYY)
made + secreted by: enteroendocrine L cells in colon + ileum
Released into: blood after eating (especially fats/proteins).
Functions:
- Reduces hunger and promotes satiety.
- Slows gastric emptying and intestinal motility (“ileal brake”).
What is Oxontymodulin (OXM), and what are its functions?
Oxontymodulin (OXM)= An anorectic peptide produced from preproglucagon.
stored/released: Stored and released from L-cells in the intestine.
Functions:
- Reduces hunger: Decreases ghrelin levels in plasma.
- Increases energy expenditure: May help burn more calories.
- Promotes weight loss: Effective in inducing weight loss.
What is Glucose-dependent insulinotropic polypeptide (GIP), and what are its functions?
GIP: An incretin hormone involved in glucose metabolism and appetite regulation.
stored/released: Stored and released by K-cells, found predominantly in the small intestine.
Functions:
- Incretin effect: Stimulates insulin release in response to food intake, particularly glucose.
- Lower levels in T2D: Circulating levels are reduced in type 2 diabetes (T2D), even after meals.
- Therapeutic target: Being explored as a target for new T2D/obesity treatments
The release of NPY activates which receptors?
The release of NPY activates Y1 receptors
n.b. if u activate NPY= increases appetite
difference between stable and unstable atherosclerotic plaque
Stable Plaque (associated with chronic, progressive disease);
- Structure: Large thick fibrous cap, foamy macrophages, small lipid core.
- Inflammation: Low.
- Risk of Rupture: Low.
- Symptoms: Gradual (e.g., stable angina).
- Management: Preventative (meds, lifestyle changes).
Unstable plaques (primary cause of acute coronary syndromes (e.g., heart attacks) and require immediate attention);
- Structure: Thin fibrous cap, large lipid core, massive deposits of cholestrol crystals too
- Inflammation: High.
- Risk of Rupture: High.
- Symptoms: Sudden (e.g., heart attack).
- Management: Emergency care (e.g., stenting, meds).
What drives leukocytes to migrate into the arterial wall in atherosclerosis? How does the body treat oxidized LDL (ox-LDL)?
Oxidized/aggregated LDL (ox-LDL).
body treats ox-LDL as a pathogen (DAMP - Danger Associated Molecular Pattern).
What is the role of HDL in atherosclerosis?
HDL removes cholesterol through reverse cholesterol transport.
Why is LDL considered unstable in the context of atherosclerosis?
LDL oxidizes spontaneously, gets trapped in the arterial wall, and is degraded by macrophages.
Explain how atherosclerosis is an inflammatory disease
Process: Leukocytes (monocytes) migrate into arterial wall due to oxidized/aggregated LDL.
Oxidized LDL (ox-LDL): Treated as a pathogen (DAMP - Danger Associated Molecular Pattern).
Monocytes: Adhere to endothelium, become macrophages, and take up ox-LDL.
HDL Role: Removes cholesterol (reverse cholesterol transport).
LDL Instability: Oxidizes spontaneously, trapped in arterial wall, and degraded by macrophages.
summary:
- Inflammation: Driven by ox-LDL.
- Macrophages: Engulf ox-LDL, contributing to plaque formation.
- HDL: Protects by removing cholesterol.
What is metabolic syndrome, and what are its key components?
Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular disease and type 2 diabetes. Its key components include:
Insulin resistance/Type 2 diabetes.
Abdominal obesity (excess fat around the waist).
Dyslipidemia (high triglycerides, low HDL cholesterol).
Hypertension (high blood pressure).
Causes: Poor diet (high in carbs/fats), lack of exercise, and genetic/ethnic factors (e.g., South Asians are 13x more likely to develop type 2 diabetes).
Management: Lifestyle changes (diet, exercise, weight loss) and medications (for blood pressure, cholesterol, blood sugar).
How does hypertriglyceridemia and excess intracellular fatty acids lead to insulin resistance and type 2 diabetes?
Excess Fatty Acids: Fatty acid transporters bring too many fatty acids into cells from blood lipids.
Mitochondrial Overload: Excess fatty acids accumulate because mitochondria can’t burn them all.
Toxic Byproducts: Saturated fatty acids are metabolized into toxic substances like ceramide.
Blocked Insulin Signaling: These toxins block insulin receptor signaling, preventing activation of GLUT4 (glucose transporter).
Reduced Glucose Uptake: Without GLUT4 activation, glucose can’t enter muscle cells, leading to insulin resistance and high blood sugar (type 2 diabetes).
Therapeutic Target: Reducing fatty acid overload or improving mitochondrial function could help treat insulin resistance.
What are GLP-1 agonists, and how do they benefit patients with diabetes or obesity in terms of cardiovascular disease (CVD)?
What are GLP-1 agonists?: They are approved medications for treating diabetes and obesity.
Mechanisms:
- Increase insulin secretion and decrease glucagon.
- Delay gastric emptying, suppress appetite, and reduce food intake.
Cardiovascular Benefits:
- Reduce CVD in patients with diabetes.
- Reduce CVD in patients with obesity (even without diabetes).
How they work in CVD:
- Reduce inflammation. Increase nitric oxide in endothelial cells (improving blood vessel function).
- Improve lipid profiles.
- Reduce blood pressure.
Where is primary urine (aka glomerular filtrate) initially accumulated in?
primary urine (aka glomerular filtrate) is initially accumulated in Bowman’s space (also known as the capsular space) of the renal corpuscle in the kidney.
Name the function/give description of the following:
- mesangial cells
- macula densa cells
- juxtaglomerular cells
- extraglomerular mesangial cells (Lacis cells)
mesangial cells= phagocytosis, structural support, modulation of glomerular distension (contractile), capable of proliferation
macula densa cells= tall narrow cells, a distinct region of the initial portion of DCT
juxtaglomerular cells= renin-producing cells adjacent to the afferent arteriole
extraglomerular mesangial cells (Lacis cells)= a space outlined by the macula densa and the arterioles (are continuous with intragolmerular mesangial cells)
Interstitial cells span between segments of the loops of Henle and adjacent vasa recta like the rung of a ladder; what are the 2 types of interstitial cell?
1) cortical fibroblasts= produce erythropoietin (EPO)
2) medullary fibroblasts= Secrete glycosaminoglycans (structural support).
Produce prostaglandin E2 (PGE₂) to regulate papillary blood flow (crucial for avsodilation)
medullary fibroblasts can be either;
- Type I Interstitial Cells: Fibroblast-like, structural (collagen/GAG secretion).
- Type II Interstitial Cells: Lipid-laden, prostaglandin-producing (PGE₂).
mnemonic: for cortical vs medullary fibroblasts: “Cortex EPO, Medulla Flow” → Cortical fibroblasts make EPO; medullary fibroblasts regulate blood flow (via PGE₂).
What is the difference between nephritic and nephrotic syndrome?
1) Nephritic Syndrome (inflammation of glomeruli)
- Hematuria (dysmorphic RBCs/casts)
- Hypertension (due to salt retention)
- Mild-moderate proteinuria (<3.5 g/day)
causes: Glomerular inflammation (e.g., IgA nephropathy, PSGN, RPGN, lupus nephritis)
Labs: ↑ Blood Urea Nitrogen (BUN) (/Creatinine (Cr), low C3 (in post-streptococcal GN)
2) Nephrotic Syndrome (Podocyte Damage)
- Massive proteinuria (>3.5 g/day)
- Hypoalbuminemia (<3 g/dL) → Oedema
- Hyperlipidemia (compensatory liver synthesis)
causes: Podocyte damage in glomeruli (e.g., minimal change disease, membranous nephropathy, Focal Segmental Glomerulosclerosis (FSGS))
Labs: Lipiduria (“oval fat bodies”), ↓ antithrombin III (↑ thrombosis risk)
Key Differences:
1) Nephritic = Blood + Inflammation (RBC casts).
2) Nephrotic = Protein + Leakage (fatty casts).
Mnemonic:
1) Nephritic → “PHAROOH”: Proteinuria, Hematuria, Azotemia, Red blood cell casts, Oliguria, Oedema, Hypertension
2) Nephrotic → “PHHL”: Proteinuria, Hypoalbuminemia, Hyperlipidemia, Lipiduria
Chronic Kidney Disease is characterised by azotemia. Define azotemia
2) What is uremia, and how does it differ from azotemia?
Azotemia refers to an elevation of nitrogenous waste products (BUN and creatinine) in the blood due to impaired kidney function.
BUN= Blood Urea Nitrogen
2) Difference between azotemia and uremia?
- Uremia is a clinical syndrome caused by severe kidney failure, where toxic waste products (e.g., urea, creatinine, uric acid) accumulate in the blood, leading to multisystem complications.
- Uremia is a severe form of azotemia where high waste product levels cause toxic symptoms.
What is nephritic syndrome?
Nephritic syndrome is kidney disease caused by the inflammation of glomeruli
causes:
- Post-streptococcal glomerulonephritis (PSGN)
- IgA Nephropathy
- Lupus Nephritis
- Rapidly Progressive Glomerulonephritis (RPGN)
labs: increase Blood Urea Nitrogen (BUN), increased creatinine (Cr) (+ low C3 in PSGN ppl)
symptoms; (PHAROOH mnemonic)
- Proteinuria
- Hematuria (blood in urine with RBC casts)
- Azotemia (elevation of nitrogenous waste products BUN/Cr)
- Red blood cell casts
- Oliguria (decreased urine output)
- Oedema
- Hypertension
what is the relationship between proteinuria and hypoalbuminaemia?
Proteinuria: Excessive protein loss in urine (>3.5 g/day), a hallmark of nephrotic syndrome.
Hypoalbuminemia: Low blood albumin levels (<3 g/dL) due to protein loss due to proteinuria
Relationship:
In nephrotic syndrome, podocyte damage causes the kidney’s filtration barrier to leak proteins, particularly albumin, into the urine (proteinuria).
Albumin loss exceeds the liver’s ability to produce more, leading to hypoalbuminemia.
Hypoalbuminemia reduces plasma oncotic pressure, causing oedema as fluid leaks into tissues.
What is the key difference between primary glomerulonephritis and secondary glomerulopathy?
1) Primary Glomerulonephritis
= Kidney is the only or predominant organ affected.
Subtypes:
- Inflammatory (e.g., IgA nephropathy, post-streptococcal GN).
- Non-inflammatory (“primary glomerulopathy,” e.g., minimal change disease).
Cause: Idiopathic or kidney-specific pathology.
2) Secondary Glomerulopathy
= Glomerular damage due to a systemic disease.
Examples:
- Autoimmune: SLE (lupus nephritis).
- Metabolic: Diabetes (diabetic nephropathy).
- Vascular: Hypertension (hypertensive nephrosclerosis).
80% of membranous glomerulonephritis is caused by what?
80% of membranous glomerulonephritis cases are primary; caused by AUTOANTIBODIES against podocyte antigens.
This is a form of chronic immune complex glomerulonephritis induced by antibodies reacting to endogenous or plated glomerular antigens
in histology membranous glomerulonephritis is characterised by subepithelial immunoglobulin-containing deposits along golmerular basement membrane
what verterbal level is each kidney
the left kidney is above (superior to) the right kidney
as the right kidney is below liver
right: T12-L4
left: T11-L3
kidneys are retroperitoneal
when a patient undergoes a kidney transplant; where is the donor kidney placed into the recipient
the donor kidney is implanted/placed into ILIAC FOSSA
renal artery and vein are connected to external iliac artery and vein
ureter is sutured into bladder
what is innervation of kidney?
The renal plexus (derived from coeliac and aorticorenal plexuses) contains:
- Sympathetic fibers from the lower thoracic and upper lumbar spinal segments (T10-L2).
Functions: - Vasoconstriction (reduces renal blood flow and filtration rate).
- Renin release from juxtaglomerular cells (regulates blood pressure).
- Decreases urine production in response to stress
- parasympathetic fibers minimal and mainly come from the vagus nerve (CN X).
Function: not understood
Clinical Significance of renal plexus:
- Sympathetic overactivity can contribute to hypertension.
- Understanding renal innervation helps in managing conditions like renal artery stenosis and hypertension. [Ref: NCBI & Nature]
what is the arterial supply and venous drainage of the ureters
ureters; are retroperitoneal muscular tubes- lie behind peritoneum
arterial supply= branches from; renal arteries, gonadal (testicular/ovarian arteries), abdominal aorta, common iliac a., internal iliac a.
venous drainage= 1) superior part via periureteric venous plexus 2) inferior part via gonadal veins
n.b. peri= around
What does “loin to groin” pain typically indicate in clinical practice?
Loin to groin pain= Sudden, severe unilateral pain radiating from the loin (flank/lower back) to the groin (or inner thigh).
Classic presentation of ureteric colic, most often caused by a kidney stone (nephrolithiasis).
Ureteric colic= ureteric pain which is often caused by renal calculus; as the calculus is forced down the ureter; referred pain will travel from loin (flank/lower back) to groin (or inner thigh); visceral pain refers to the ipsilateral dermatome in T11-L2 range (depending on stone location)
Cause: Obstruction (e.g., calculi, blood clot) → ureteral spasm + distension.
Other causes: Pyelonephritis (bacterial infection of the kidneys), renal infarction.
Associated Symptoms:
- Nausea/vomiting, hematuria, urinary urgency.
- No fever (if fever + flank pain → suspect pyelonephritis).
Diagnosis:
- Non-contrast CT (gold standard for stones).
- Urinalysis: Hematuria (90% of cases).
Clinical point:
- Peritoneal signs (e.g., rebound tenderness) are absent—helps distinguish from surgical abdomen.
- Pregnant women with pyelonephritis require IV antibiotics (risk of preterm labor).
What is rebound tenderness, and what does it indicate?
Rebound tenderness is pain upon sudden release of pressure during abdominal palpation, signaling peritoneal inflammation (e.g., peritonitis).
Mechanism:
Irritated peritoneum snaps back after compression → sharp pain.
Key Causes:
- Acute Appendicitis (McBurney’s point).
- Perforated Ulcer (sudden generalized pain).
- Diverticulitis (LLQ in sigmoid cases).
- Cholecystitis (RUQ, + Murphy’s sign).
How to Test:
1) Press deeply on abdomen (away from pain).
2) Quickly release → positive if patient winces.
Clinical Significance:
- Surgical emergency if present (e.g., perforation).
- Absent in renal colic (helps distinguish from pyelonephritis).
what is choledocholithiasis?
Choledocholithiasis = Presence of gallstones in the common bile duct (CBD), obstructing bile flow.
Causes:
- Primary: Stones form directly in CBD (rare, often pigmented stones in hemolytic diseases).
- Secondary: Stones migrate from gallbladder (most common, cholesterol stones).
Symptoms: Classic Triad (Charcot’s Triad):
1) RUQ pain (biliary colic).
2) Jaundice (obstructive → dark urine, pale stools).
3) Fever/chills (if ascending cholangitis).
Severe cases: Reynolds’ Pentad (Charcot’s + hypotension + AMS) → emergent!
Diagnosis:
Labs: ↑ ALP, ↑ bilirubin (direct), ↑ AST/ALT (mild).
Imaging:
Ultrasound (1st-line, detects duct dilation).
Complications:
- Ascending cholangitis (life-threatening infection).
- Pancreatitis (if stone blocks pancreatic duct).
- Biliary cirrhosis (chronic obstruction).
Treatment:
- ERCP (stone removal + stent if needed).
- Cholecystectomy (prevents recurrence if gallbladder stones present).
What does AMS (Altered Mental Status) mean, and what are common causes?
AMS = Altered Mental status (acute change in cognition, awareness, or behavior, ranging from confusion to coma)
Common Causes
- Alcohol/toxins (e.g., ethanol, opioids)
- Electrolytes (e.g., hyponatremia, hypercalcemia)
- Infection (e.g., sepsis, UTI in elderly, meningitis)
- Oxygen lack (e.g., hypoxia, stroke)
- Uremia (kidney failure)
- Trauma (head injury)
- Ictal (seizure/post-ictal)
- Psychiatric (e.g., psychosis)
- Sugar (hypo-/hyperglycemia)
CVA tenderness (Costovertebral Angle tenderness) is pain elicited by percussion over the angle between the 12th rib and the spine (flank region).what is
CVA tenderness (Costovertebral Angle tenderness) is pain elicited by percussion over the angle between the 12th rib and the spine (flank region).
Clinical Significance:(THINK KIDNEY)
Indicates kidney involvement, seen in:
- Pyelonephritis (kidney infection).
- Renal colic (kidney stone obstruction).
- Perinephric abscess (rare).
Key Differential:
- Musculoskeletal pain: Tender to palpation but not percussion.
- Biliary disease: Pain is in the RUQ, not flank.
N.B. Unilateral CVA tenderness + fever → Pyelonephritis until proven otherwise!
Where is bile produced and stored in the body?
Bile Production:
Made in the liver by hepatocytes.
Secreted into bile canaliculi → flows into bile ducts → stored/concentrated in the gallbladder.
Bile Storage:
Gallbladder (a pear-shaped sac under the liver).
Concentrates bile by absorbing water/electrolytes.
Releases bile into the duodenum via the common bile duct (CBD) when stimulated by cholecystokinin (CCK) (e.g., after a fatty meal).
Key Bile Pathway:
Liver → Hepatic ducts → Cystic duct (to gallbladder) → CBD → Ampulla of Vater → Duodenum.
what are the 3 most common points kidney stones get stuck and why?
get stuck at narrowings/constrictions
- Ureteropelvic junction (UPJ)
- Crosses common iliac vessels (pelvic brim)
- where the ureter enters wall of bladder aka Ureterovesical Junction (UVJ)
what is a patent urachus + symptoms in neonates
A patent urachus is a congenital anomaly where the urachus (a fetal duct connecting the bladder to the umbilicus) fails to close after birth, leading to a persistent connection between the bladder and umbilicus.
- The urachus normally closes before birth to become the median umbilical ligament.
- In a patent urachus, the channel remains open, leading to leakage.
🟢 Symptoms in Neonates:
- Umbilical Discharge: Urine leaking from the umbilicus.
- Recurrent UTIs: Due to contamination.
- Skin Irritation & Redness around the umbilicus.
- Crying During Urination: Discomfort due to leakage.
in acute urinary retention, the surgeon can insert a needle suprapubically without worrying about hitting the peritoneum; why is this?
as the bladder expands, the peritoneum is lifted away from the anterior face of the urinary bladder. Therefore, a needle inserted here suprepubically, will not breach the boundary of the peritoneal cavity
How do the sympathetic, parasympathetic, and somatic nervous systems regulate bladder filling and emptying?
- Sympathetic (T10–L2, Hypogastric Nerve):
Controls Bladder Filling:
- Contracts internal urethral sphincter (α1-receptors).
- Relaxes detrusor muscle (β3-receptors).
- Prevents voiding (unwanted peeing/micturition) during bladder filling. - Parasympathetic (S2–S4, Pelvic Nerve):
Controls Bladder Emptying:
- Contracts detrusor muscle (muscarinic M3 receptors).
- Relaxes internal urethral sphincter. - Somatic Motor (S2–S4, Pudendal Nerve):
Under Voluntary Control:
- Tonic contraction of external urethral sphincter (voluntary override= consciously hold your pee in).
- Relaxation permits voiding.
Sensory Input:
- Stretch receptors (bladder wall, trigone) signal fullness via pelvic nerve → spinal cord → brain (pontine micturition center).
what are the 2 types of pyelogram and the differences
“Pyelo-”: Derived from the Greek word “pyelos” meaning “pelvis’
PYELOGRAM is imaging of renal pelvis and ureters!
1) intravenous pyelogram= contrast excreted by kidneys, shows functioning of kidneys
2) retrograde pyelogram= contrast inserted via urethra, can see urinary tract
The mammillary bodies are located in the hypothalamus. What happens when they are damaged e.g. in Korsakoff’s syndrome due to thiamine deficiency
Damage to the mammillary bodies, and their projections via the mammillothalamic tract, result in episodic and recollective memory impairments in patients and spatial memory impairments
What are the primary hormones secreted by the anterior pituitary gland (adenohypophysis), and what are their main functions?
Anterior Pituitary Hormones:
Growth Hormone (GH):
Function: Stimulates growth of bones and tissues; regulates metabolism.
Secreted by: Somatotrophs.
Thyroid-Stimulating Hormone (TSH):
Function: Stimulates the thyroid gland to produce thyroid hormones (T3 and T4).
Secreted by: Thyrotrophs.
Adrenocorticotropic Hormone (ACTH):
Function: Stimulates the adrenal cortex to release cortisol
Secreted by: Corticotrophs.
Follicle-Stimulating Hormone (FSH):
Function: Stimulates ovarian follicle maturation in females; spermatogenesis in males.
Secreted by: Gonadotrophs.
Luteinizing Hormone (LH):
Function: Triggers ovulation and corpus luteum formation in females; stimulates testosterone production in males.
Secreted by: Gonadotrophs.
Prolactin (PRL):
Function: Promotes milk production in breastfeeding females.
Secreted by: Lactotrophs.
What are the primary hormones secreted by the posterior pituitary gland (neurohypophysis), and what are their main functions?
Posterior Pituitary Hormones:
Antidiuretic Hormone (ADH/Vasopressin):
Function: Regulates water balance by reducing urine output; constricts blood vessels to raise blood pressure.
Produced by: Hypothalamic neurons; stored and released by the posterior pituitary.
Oxytocin:
Function: Stimulates uterine contractions during childbirth; promotes milk ejection during breastfeeding.
Produced by: Hypothalamic neurons; stored and released by the posterior pituitary.
difference between Cushing’s disease and Cushing’y syndrome
Cushing’s disease is caused by excess ACTH from a pituitary adenoma, while Cushing’s syndrome refers to excess cortisol from any cause.
Enlargement of the pituitary gland superiorly or a pituitary tumour/ adenoma can compress the optic chiasm and lead to a characteristic visual field defect. What is the defect?
bitemporal hemianopia is a consequence of pituitary adenoma
A 34 year old man has end stage kidney failure and requires dialysis.
What substance is most likely to be decreased because of his condition?
1,25-dihydroxyvitamin D deficiency because In end-stage kidney failure, the kidneys lose their ability to efficiently convert 25-dihydroxyvitamin D to 1,25-dihydroxyvitamin D
Thrombocytopenia (the reduction of platelet count in blood) is a common haematological complication of alcoholic liver cirrhosis.
What mechanism typically represents the main cause of thrombocytopenia (low platelets) in a patient with this type of liver disease?
Haemolysis in the enlarged spleen and decreased production thrombopoietin in the liver
Bowman’s capsule is the filtering unit of the kidneys.
Which embryonic structure does it originate from?
Metanephric blastema
What are the embryonic origins and development timelines of the anterior and posterior pituitary glands?
Anterior Pituitary (Adenohypophysis):
Origin: Rathke’s pouch (ectodermal outpocketing from the roof of the mouth).
Development Timeline:
- 4th Week: Rathke’s pouch formation.
- 5th to 6th Week: Growth towards the brain; differentiation into pars distalis, pars intermedia, and pars tuberalis.
Posterior Pituitary (Neurohypophysis):
Origin: Infundibulum (downward extension from the diencephalon).
Development Timeline:
- 4th to 8th Week: Infundibulum elongates, forming the pituitary stalk and pars nervosa.
- By the 12th to 16th week, the anterior pituitary starts hormone production (e.g., GH, ACTH)
Severe dwarfism resulting from PUOF1 (Pit 1) mutation means what hormones is the person deficient in?
Mutations in the POU1F1 gene, also known as Pit-1, lead to Combined Pituitary Hormone Deficiency (CPHD), characterized by deficiencies in the following hormones:
= missing prolactin, growth hormone and TSH
Individuals with POU1F1 mutations often present with severe growth retardation from infancy, central hypothyroidism, and may exhibit distinctive facial features such as a prominent forehead and mid-facial hypoplasia
A 50 year old man is being investigated for acromegaly and undergoes an oral glucose tolerance test. The clinician is monitoring the variation in a specific hormone.
What change in the levels of which hormone is expected during this test if the patient has acromegaly?
acromegaly is caused by excess Growth Hormone (GH).
the oral glucose tolerance test can be used to test for acromegaly. The healthy response (someone without acromegaly during the OGTT, the blood glucose level rise, and this leads to a suppression of growth hormone (GH) secretion.
In patietns with acromegaly the GH levels will remain UNCHANGED/ the same
In a patient with acromegaly: The key abnormality in acromegaly is excessive GH secretion, usually due to a pituitary adenoma.
Levothyroxine (T4) suppreses what hormone
Levothyroxine (T4) suppresses TSH (thyroid-stimulating hormone).
what time of day are Growth Hormone (GH) highest? How do we measure GH usually?
Growth Hormone (GH) levels are highest during deep sleep, particularly during slow-wave sleep (SWS) in the first few hours of the night
We acc measure IGF (insulin-like growth factor) as its more reliable at indicating GH levels. GH Stimulates IGF-1 Production; so if IGF-1 is high we can assume GH is high too.
- GH Secretion is Pulsatile: GH fluctuates throughout the day, making it hard to measure accurately.
- IGF-1 Levels are More Stable: IGF-1 has a longer half-life (about 12-16 hours), providing a more consistent indicator of GH activity over time.
Disorders:
Acromegaly or Gigantism: High IGF-1 + High GH = Excess GH Production
GH Deficiency: Low IGF-1 + Low GH = GH Deficiency
What is GHRH; where is it produced + function. Pathology seen in GHRH deficienct vs GHRH excess
Growth Hormone Releasing hormone; - -Produced in: Arcuate nucleus of the hypothalamus
Released into: Hypothalamo-hypophyseal portal system
Acts on: Somatotrophs in the anterior pituitary gland
GHRH binds to the GHRH receptor (a G protein coupled receptor) and stimulates Growth Hormone (GH) release from the anterior pituitary
pathology:
GHRH Deficiency: Can lead to GH deficiency and short stature
Excess GHRH: Linked to acromegaly and gigantism
what mutation is McCune-Albright syndrome caused by?
McCune-Albright syndrome caused by mutation in GNAS gene
McCune-Albright syndrome is a rare genetic disordered originally recognized by the triad of polyostotic fibrous dysplasia, precocious puberty, and cafe-au-late spots. A variety of endocrine disorders, including hyperthyroidism, acromegaly, phosphate wasting, and Cushing syndrome are now considered as part of the endocrinopathies seen in this disorder.
Somatostatin (SS) function + clinical relevance
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH), is a peptide hormone produced in the hypothalamus, pancreatic delta cells, and gastrointestinal tract. It primarily acts as an inhibitory hormone but has some indirect stimulatory effects.
INHIBITS ALL OF THESE: Growth Hormone (GH), Thyroid-Stimulating Hormone (TSH), Prolactin (PRL), Gastrin, Cholecystokinin (CCK), Secretin, Motilin, Vasoactive Intestinal Peptide (VIP), Insulin, Glucagon
Clinical relevance:
- Synthetic analogs (e.g., Octreotide) are used in acromegaly, carcinoid syndrome, and GI bleeding due to their inhibitory effects.
- Somatostatin analogs can control hormone-secreting tumors (e.g., GH in acromegaly)
mutation in what gene causes the most profound gigantism (tallest man in the world has it)
GPR101 mutation cause the most profound cases of gigantism, specifically a rare condition known as X-linked acrogigantism (XLAG)
- GPR101 is a G-protein-coupled receptor gene located on the X chromosome.
- It’s primarily expressed in the pituitary gland and hypothalamus.
HPA Axis (Hypothalamo-Pituitary-Adrenal Axis)
HPA axis= regulates stress response, mood, and energy metabolism.
Key Hormones & Pathway:
- CRH (Corticotropin-Releasing Hormone) from the hypothalamus stimulates the pituitary gland.
- ACTH (Adrenocorticotropic Hormone) from the pituitary gland stimulates the adrenal gland.
- Cortisol from the adrenal gland provides feedback inhibition to the hypothalamus and pituitary to reduce CRH and ACTH release.
- Arginine-Vasopressin (AVP) from the hypothalamus can enhance ACTH release.
Clinical Conditions:
- Cushing’s Syndrome: High cortisol (due to excess ACTH or cortisol production).
- Addison’s Disease: Low cortisol (due to adrenal insufficiency).
Feedback Mechanism:
- Cortisol exerts negative feedback on CRH and ACTH release to maintain balance.
what neurons make kisspeptin, neurokinin B and dynorphin
the KNDy neurons make kisspeptin, neurokinin B and dynorphin
how is prostate and breast cancer treated?
prostate and breast cancer is treated with GnRH analogues
What is Hypergonadotropic hypogonadism (HH)
Hypergonadotropic hypogonadism (HH)= body produces insufficient sex hormones despite high levels of gonadotropins (high LH, high FSH, low testosterone, low oestrogen)
what is Kallman syndrome symptoms and cause
Kallmann syndrome is a rare genetic disorder characterized by a combination of hypogonadotropic hypogonadism and anosmia.
caused by mutation in KAL1 protein (anosmin)
symptoms:
-Delayed or Absent Puberty
- Anosmia or Hyposmia (Impaired Sense of Smell)
- Infertility/ low libido
- when asked to move one hand the other hand mimics
- tall stature (+ long limbs)
What is diabetes insipidus
Diabetes insipidus is characterised by deficiency or improper function of ADH/ vasopressin= dysregulated water balance= excessive urination (polyuria) and intense thirst (polydipsia)
different types:
- Central Diabetes Insipidus (Neurogenic DI):
cause: ADH deficiency due to damage to the hypothalamus or pituitary gland.
- Nephrogenic Diabetes Insipidus:
cause: Kidneys fail to respond to ADH, even if levels are normal or high - Dipsogenic Diabetes Insipidus (Primary Polydipsia):
cause: Excessive water intake suppresses ADH. - Gestational Diabetes Insipidus:
cause: During pregnancy, an enzyme from the placenta breaks down ADH. (this type is treated with Desmopressin (DDAVP); an ADH analogue)
Barts health uses MUST and STAMP to identify patients at risk of malnutrition what do these stand for? Define malnutrition
MUST= ‘Malnutrition Universal Screening Tool’
STAMP= ‘Screening Tool for the Assessment of Malnutrition in Paediatrics’
THESE NEED TO COMPLETED WITHIN 6 HOURS ON PATIENTS OF CONCERN
malnutrition= a state of nutrition in which a deficiency or excess of energy, protein and other nutrients causes measurable adverse effects on tissue + clinical outcome
Mid-arm circumference (MUAC) is used to measure BMI if we aren’t able to weigh someone. What are the estimated BMI measurements for the MUAC?
if MUAC <23.5 then patient likely underweight (<20 BMI)
if MUAC >32 then patient likely overweight (>30 BMI)
Clinical Consequences of Hypophosphataemia
Hypophosphataemia
Neurological: Seizures, paraesthesia
Musculoskeletal: Rhabdomyolysis, weakness, osteomalacia
Respiratory: Impaired respiratory muscle function
Cardiac: Cardiac failure
Renal: Rhabdomyolysis, fluid and salt retention
Clinical Consequences of Hypomagnesaemia
Hypomagnesaemia
Neurological: Tetany, paraesthesia, seizures, ataxia, tremor
Cardiac: Arrhythmias
Gastrointestinal: Anorexia, abdominal pain
Clinical Consequences of Hypokalaemia
Hypokalaemia (can be a consequence of diuretics, vomiting, diarrhea)
Neurological: Paralysis, paraesthesia
Musculoskeletal: Rhabdomyolysis
Respiratory: Respiratory depression
Cardiac: Arrhythmias, cardiac arrest
Gastrointestinal: Constipation, paralytic ileus
Reefeeding syndrome summary
Refeeding Syndrome
Cause: Rapid nutrition after starvation → insulin surge → intracellular shift of K⁺, Mg²⁺, PO₄³⁻ → severe hypokalemia, hypomagnesemia, hypophosphatemia.
Key Risks:
- Cardiac: Arrhythmias (torsades, VT/VF), heart failure (fluid overload).
- Neuro/Muscular: Seizures, weakness, rhabdo, respiratory failure.
- Thiamine deficiency → Wernicke’s encephalopathy.
at risk patients: Anorexia, alcoholism, prolonged fasting, malnourished patients
Prevention & Treatment:
- Start slow: ≤50% kcal needs initially, increase gradually.
Electrolytes:
- Pre-feed correction: PO₄³⁻, K⁺, Mg²⁺ (check levels first!).
- Monitor closely (daily labs initially).
- Thiamine (IV) before glucose to prevent Wernicke’s.
- Avoid fluid overload (insulin causes Na⁺/H₂O retention).
Classic Triad:
⚠️ Hypophosphatemia + Hypokalemia + Hypomagnesemia
Phenylketonuria (PKU)
Detected via heel-prick test (Guthrie test)
Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase (PAH).
This enzyme converts phenylalanine (Phe) → tyrosine (Tyr).
Result: Toxic buildup of phenylalanine, leading to intellectual disability, seizures, and behavioral issues if untreated.
Treatment:
- Lifelong low-phenylalanine diet (avoid high-protein foods: meat, eggs, dairy).
- Tyrosine supplementation (essential amino acid).
- BH4 (tetrahydrobiopterin) therapy for some mild forms.
what is the difference between serum and plasma and when would u use which test?
Plasma:
- Contains anticoagulants (e.g., heparin, EDTA).
- Fibrinogen present (clotting factors retained).
- Prepared immediately after mixing.
- Less stable (long-term storage may alter ions).
- May contain WBCs/platelets (risk of contamination).
Serum:
- No anticoagulants (clot forms naturally).
- Fibrinogen absent (consumed during clotting).
- 30-minute delay for clot formation.
- More stable (gold standard for biobanking).
- Higher K⁺ (clot retraction releases intracellular K⁺).
When to Use Which?
Plasma:
- Coagulation tests (e.g., PT, aPTT).
- Ammonia, lactate (needs rapid processing).
Serum:
- Most routine biochemistry (e.g., electrolytes, enzymes).
- Long-term research storage.
Apoprotein B (LDL) + Apoprotein A (HDL) are measured as what kind of ratio and why is it used to assess lipid-associated CV risk?
ApoB/ApoA ratio carries a better diagnostic value of lipid-associated CV risk than total cholesterol or HDL
Liver Function Test Indicators; what does each indicate:
- AST>ALT
- ALT>AST
- elevated ALP
- elevated GGP
- elevated bilirubin
- low albumin
- prolonged Prothrombin Time (PT)/INR
AST > ALT (AST/ALT ratio > 1):
- Alcoholic Liver Disease: AST/ALT ratio > 2:1
- Cirrhosis: Elevated AST/ALT ratio in chronic hepatitis suggests cirrhosis
- Advanced Fibrosis: Higher AST/ALT ratio reflects disease progression
ALT > AST (AST/ALT ratio < 1):
- Acute Viral Hepatitis: Significantly higher ALT than AST
- NAFLD: Lower AST/ALT ratio common.
Alkaline Phosphatase (ALP): Elevated in cholestasis or bile duct obstruction.
Gamma-Glutamyl Transferase (GGT): Increased in alcohol use or biliary disease
Bilirubin: High levels indicate liver dysfunction, hemolysis or bile duct obstruction.
Albumin: Low levels suggest chronic liver disease.
Prothrombin Time (PT)/INR: Prolonged times indicate impaired liver function.
what symptoms directly necessitate a LFT
- Jaundice (yellowing of skin + eyes)
- nausea/vomiting
- diarrhoea
- abdominal pain
- dark-coloured urine
- light-coloured stool
- fatigue
mutation in what genes causes Gilbert syndrome
Changes in the UGT1A1 gene cause Gilbert syndrome. This gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme
what is the most important test for kidney function
estimated GFR (eGFR)
looks at creatinine clearance from plasma to estimate the filtration rate
what do the following cancer antigens screen for
PSA
CA-125
CA15-3 + CA27-29
AFP
PSA= prostate cancer (high in specificity but not sensitivity so can have false negative)
CA-125= cancer antigen-125; used for prognosis of ovarian cancer. N.b. High CA-125 can also result from menstrual changes, uterine fibroids, endometrial, fallopian and peritoneal cancers
CA15-3 + CA27-29= breast cancer antigens used to monitor treatment in advance breast cancer
AFP (Alpha-fetoprotein)= used to diagnose liver cancer, and monitor treatment
Types of hyperthyroidism
Types of hyperthyroidism:
Primary;
Thyroid gland secretes excess T3 and T4 hormone
TRH reduced, TSH reduced, T3 & T4 raised
Secondary;
Pituitary gland secretes excess thyroid-stimulating hormone (TSH)
TRH reduced, TSH raised, T3 & T4 raised
Tertiary;
Hypothalamus secretes excess thyrotropin-releasing hormone (TRH)
TRH raised, TSH raised, T3 & T4 raised
what structure connects the stomach to the duodenum?
The pylorus is the part of the stomach that connects the stomach to the small intestine (duodenum).
what is Liddle syndrome
Liddle syndrome is an autosomal dominant condition affecting the regulation of ENaC. These channels are expressed by principle cells on the apical membrane of the DCT and the collecting duct. In Liddle syndrome, degradation of ENaC is compromised, resulting in excessive sodium reabsorption. This increases plasma volume and results in the development of hypertension. To maintain a neutral electrochemical gradient, positively charged potassium ions are expelled into the urine which additionally causes hypokalaemia to develop.
