Case 17

Question 1

What is Type 1 Diabetes?

Answer 1

Type 1 diabetes is an autoimmune disorder where the body’s immune system attacks and destroys insulin-producing beta cells in the pancreas, leading to insulin deficiency.

Question 2

What causes Type 1 Diabetes?

Answer 2

Type 1 diabetes is primarily caused by an autoimmune response that destroys beta cells in the pancreas. Genetic predisposition and environmental factors like viral infections can trigger the onset.

Question 3

How does Type 1 Diabetes affect insulin production?

Answer 3

In Type 1 diabetes, the immune system attacks the pancreas, specifically the beta cells, leading to little or no insulin production. Without insulin, glucose cannot enter cells, causing high blood sugar.

Question 4

What are the main symptoms of Type 1 Diabetes?

Answer 4

Common symptoms include polyuria (frequent urination), polydipsia (excessive thirst), polyphagia (increased hunger), fatigue, weight loss, and blurred vision.

Question 5

How is Type 1 Diabetes diagnosed?

Answer 5

Type 1 diabetes is diagnosed based on blood glucose tests, such as a random blood glucose level of ≥11.1 mmol/L, fasting glucose ≥7 mmol/L, or an HbA1c of ≥48 mmol/mol. Testing for autoantibodies is also common.

Question 6

What is the treatment for Type 1 Diabetes?

Answer 6

The primary treatment for Type 1 diabetes is lifelong insulin therapy. Insulin can be administered through injections or an insulin pump. Patients also need to monitor blood glucose levels, maintain a balanced diet, and exercise.

Question 7

What are the potential complications of Type 1 Diabetes?

Answer 7

Complications include diabetic ketoacidosis (DKA), cardiovascular disease, nephropathy (kidney damage), retinopathy (eye damage), neuropathy (nerve damage), and increased risk of infections.

Question 8

What is Diabetic Ketoacidosis (DKA)?

Answer 8

DKA is a life-threatening complication of Type 1 diabetes, where the body starts breaking down fat for fuel, producing ketones. Ketones accumulate in the blood, leading to acidosis. Symptoms include nausea, vomiting, abdominal pain, and confusion.

Question 9

At what age is Type 1 Diabetes typically diagnosed? VS Type 2

Answer 9

Type 1 diabetes is usually diagnosed in children, adolescents, or young adults, though it can occur at any age.

Type 2 diabetes is more commonly diagnosed in adults over 45 years old, although it is increasingly seen in younger individuals, especially with rising obesity rates.

Question 10

How does insulin production differ in Type 1 and Type 2 Diabetes?

Answer 10

In Type 1 diabetes, there is little to no insulin production because of beta cell destruction. In Type 2 diabetes, insulin production may be normal initially, but the body’s cells become resistant to it.

Question 11

Is there a genetic predisposition for Type 1 or Type 2 Diabetes?

Answer 11

Both types have a genetic component, but Type 1 diabetes is strongly linked to autoimmune conditions and genetic susceptibility. Type 2 diabetes is more commonly influenced by lifestyle factors (e.g., diet, physical activity) and a family history of the condition.

Question 12

What is the risk of developing Diabetic Ketoacidosis (DKA) in Type 1 vs Type 2 Diabetes?

Answer 12

Diabetic ketoacidosis (DKA) is more common in Type 1 diabetes, especially if insulin is missed or not enough is taken. It is rare in Type 2 diabetes but can occur in extreme cases, often when combined with infection or other stressors.

Question 13

Differences between Type 1 and Type 2

Answer 13

Question 14

What is the functional unit of the kidney and how many are there in each kidney approx

Answer 14

Functional unit is called a nephron and there are usually 1 millions nephrons in each kidney

Question 15

What are the kidneys, and what is their primary function?

Answer 15

The kidneys are two bean-shaped organs located in the back of the abdominal cavity. Their primary functions include:

• Filtering blood to remove waste products and excess substances, forming urine.
• Regulating electrolytes (e.g., sodium, potassium, and calcium).
• Maintaining fluid balance by adjusting water retention or excretion.
• Regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS).
• Erythropoiesis: Producing the hormone erythropoietin to stimulate red blood cell production in response to low oxygen levels.
• Acid-base balance: Regulating pH by excreting hydrogen ions and reabsorbing bicarbonate.
• Has a role in vitamin D activation

Question 16

What do nephrons do

Answer 16

Filter blood plasma.

Reabsorb essential substances like glucose and water.

Secrete waste products and excess ions.
Nephrons ensure the body maintains homeostasis by regulating fluid and electrolyte balance, blood pressure, and pH levels.

Question 17

What is the path that filtrate takes as it travels through the nephron?

Answer 17

Blood is filtered in the glomerulus.

Filtrate enters the Bowman’s capsule.

It flows through the proximal convoluted tubule (PCT).

Descends into the Loop of Henle (descending limb).

Ascends through the Loop of Henle (ascending limb).

Passes through the distal convoluted tubule (DCT).

Enters the collecting duct, which carries it to the renal pelvis as urine.

Question 18

Explain the blood flow through the kidney

Answer 18

Renal artery —> Segmental artery –> Interlobar artery —> Arcuate artery —> Interlobular —> Afferent arterioles —> Glomerular capillaries —> Efferent arterioles –> Vasa recta / Peritubular (wraps around the renal tubules) —> Interlobular vein —> etc. until renal vein

Question 19

What makes renal blood flow special from other organs

Answer 19

• Renal blood flow is not metabolically regulated
• Metabolic Regulation of Blood Flow (in General):
  In most organs, blood flow is tightly coupled to the metabolic demands of the tissue. For example, muscles receive increased blood flow during exercise because their oxygen and nutrient requirements rise.

This is called metabolic regulation, where blood flow is matched to the tissue’s oxygen and energy needs.

• Renal Blood Flow is Different
  The kidneys receive a disproportionately large amount of blood—20–25% of cardiac output, far exceeding their metabolic requirements.

This high blood flow is not to meet the metabolic needs of kidney tissue but to support the filtration of blood and the removal of waste products.

The primary purpose of renal blood flow is to deliver plasma for filtration at the glomeruli, enabling the kidneys to maintain homeostasis.

Question 20

What is the role of the glomerulus in the nephron and its structure

Answer 20

Structure of the Glomerulus
- Capillary Network: The glomerulus consists of fenestrated capillaries (capillaries with tiny pores) that allow for the passage of water and small solutes while preventing larger molecules like proteins and blood cells from passing.
- Basement Membrane: Beneath the endothelial cells of the capillaries is a basement membrane, which is a dense layer that serves as the primary filtration barrier.
- Podocytes: These are specialized cells with foot-like extensions (pedicels) that wrap around the capillaries. The spaces between the pedicels, called filtration slits, allow filtrate to pass while restricting larger molecules.

The Role of Charge in Filtration
- The basement membrane and the podocytes are coated with negatively charged glycoproteins.
- This negative charge repels negatively charged molecules, such as proteins (e.g., albumin), further preventing them from entering the filtrate.
- This selective barrier ensures that only water, electrolytes, glucose, amino acids, and small waste products like urea can pass into the Bowman’s capsule.

Question 21

Describe the physiology behind the filtration process of the nephron

Answer 21

Filtration Process
- Blood Flow and Pressure: Blood enters the glomerulus via the afferent arteriole and exits through the efferent arteriole. The afferent arteriole has a larger diameter than the efferent arteriole, creating high pressure within the glomerular capillaries.

• Hydrostatic Pressure: This pressure forces plasma and small solutes through the filtration barrier (endothelium, basement membrane, and filtration slits of podocytes) into the Bowman’s capsule.
• Filtrate Composition: The resulting filtrate, called glomerular filtrate, contains water, glucose, amino acids, ions, and metabolic waste products like urea, but no proteins or blood cells in a healthy kidney.

Question 22

What is the glomerular filtration rate forces equation and what does each factor do to filtration

Answer 22

Kf = filtration coefficient (not very important) (usually constant in healthy people)

Pgc = glomerular capillary hydrostatic pressure (created by size of afferent arteriole) (main driver of filtration) (favours filtration)

piGC = glomerular capillary oncotic pressure (blood has proteins and salts means high conc = low water potential so water wants to move into blood so it opposes filtration) (effectively zero under normal conditions)

Pbc = Bowman’s capsule hydrostatic pressure (has its own hydrostatic pressure and it will ofc oppose filtration) (because the pressure its exerting is away from itself and into the blood which will oppose filtration of blood into the Bowman’s capsule)

Question 23

What is Autoregulation and why does it happen

Answer 23

Autoregulation refers to the kidney’s intrinsic ability to maintain a relatively stable renal blood flow (RBF) and glomerular filtration rate (GFR) despite changes in systemic blood pressure. This ensures that the kidneys can perform essential functions, such as filtering blood, maintaining fluid and electrolyte balance, and regulating blood pressure, even under varying physiological conditions.

Question 24

What are the two mechanism behind autoregulation

Answer 24

• Myogenic tone
• Tubuloglomerular feedback

Question 25

How does the Myogenic tone for autoregulation work

Answer 25

Vascular smooth muscle in the walls of the afferent arteriole responds to changes in blood pressure. When blood pressure increases, the arteriole stretches. Smooth muscle responds by contracting to reduce blood flow into the glomerulus (vasoconstriction). When blood pressure decreases, the arteriole relaxes (vasodilation), allowing more blood to flow into the glomerulus. * Efferent arteriole tone remains constant helping to stabilise the net filtration pressure * This works to maintain glomerular arterial pressure at all times Purpose: Prevents excessive pressure in the glomerulus during hypertension.

Question 26

How does Tubuloglomerular feedback for autoregulation work

Answer 26

When arterial pressure increases, glomerular pressure and plasma flow increase, leading to a rise in GFR. This raises NaCl concentration in the early distal tubule, detected by the macula densa. The macula densa responds by releasing paracrine signals (like ATP, adenosine) that cause constriction of the afferent arteriole. This increases preglomerular resistance, lowering glomerular pressure and returning GFR towards normal.

Question 27

What cells in the distal convoluted tubule sense NaCl concentration

Answer 27

Macula dense cells

Question 28

How do u calculate GFR via renal clearance

Answer 28

You use this formula of renal clearance

Question 29

What factors must the ideal marker for measuring GFR via renal clearance have

Answer 29

- Must be freely filtered into the nephron - Must not be reabsorbed - Must not have any more of that substance be secreted into the nephron outside the glomerulus - Must be all excreted into the urine

Question 30

What are the markers used for GFR

Answer 30

- The most clinically used is Creatinine, it meets pretty much all the conditions (except a little is secreted into the nephron in the distal part of the nephron but its negligible). However it is affected by diet, gender, age and ethnicity - Gold standard is a substance called Inulin, however it is not produced endogenously and instead produced by a plant and so must be infused into the blood, this is impractical for humans but its used for research and testing in animals.

Question 31

What is the percentage of sodium absorbed in different parts of the nephrons

Answer 31

- Bulk is in the late PCT (67%( - Loop of henle (25%) - Fine tuning via the hormone Aldosterone in DCT and collecting duct (8%)

Question 32

Explain sodium absorption in late PCT

Answer 32

Basolateral Na*/K* ATPase: * Pumps 3 Nat out, 2 k* in * Maintains low intracellular Na* → creates gradient for apical uptake Apical transporters: * NHE-3 (SLC9A3): Na*/H* exchanger (main one) * Na in, H+ out * After H+ leaves it binds with filtered HCO3 → forms H20 + CO2 * CO2 then diffuses in → recombines into H* and HCO3- (so H+ is always recycled) The movement of Na+ creates an electrochemical gradient that drives Cl reabsorption CI reabsorption: Cl/anion exchanger: * Cl moves into cell in exchange for HCO3- * Cl exits via basolateral Cl channels * Bicarbonate reabsorption: H* recycling enables recovery of filtered HCO3 * A basolateral Nat/H* exchanger (NHE-1 / SLC9A1) is also present, but it primarily functions in cell volume regulation, not sodium reabsorption.

Question 33

Explain sodium absorption in DCT and collecting duct and how aldosterone works

Answer 33

In the DCT and collecting duct is where we fine tune the amount of Na absorbed Reabsorption in the DCT & collecting duct unlike in the PCT, It is controlled primarily by aldosterone which is released by the adrenal cortex in response to: * Increased Angiotensin II (e.g., in hypovolaemia) * Increased Plasma K* concentration * Aldosterone then causes: - Increased transcription and insertion of ENaC (epithelial Na+ channels) on the apical membrane, this Allows Na+ to enter the cell down its gradient. (this is a slow process 24-48hrs) - Aldosterone also upregulates activity of Na*/K* ATPase on the basolateral membrane which pumps reabsorbed Na+ into the blood in exchange for K*. It also Increases apical K* channels which promotes K+ secretion into the tubular fluid (excretion of K+)

Question 34

Where is Glucose mostly reabsorbed

Answer 34

PCT (most in the early proximal (bulk), and the rest is in late proximal tubule)

Question 35

Explain glucose reabsorption in the nephron

Answer 35

Question 36

What is the transporter responsible for the majority of sodium reabsorption

Answer 36

NHE-3 (second is ENaC)

Question 37

Describe what permeability of the descending loop of henle to water and Na/Cl

Answer 37

Descending loop of henle is impermeable to Na/Cl and permeable to water, allowing water to be reabsorbed and concentrating the urine

Question 38

Describe what permeability of the ascending loop of Henle to water and Na/Cl

Answer 38

Permeable to Na/Cl but impermeable to water allowing which means Na/Cl can leave the urine and be reabsorbed but water can't go back in which dilutes the urine

Question 39

Explain the concentration then dilution of urine in the loop of henle (under healthy conditions)

Answer 39

- Proximal tubule: reabsorbs water and Na+ in equal proportions → tubular fluid remains isotonic (300 mOsm/kg). - Descending limb of loop of Henle: Permeable to water only Water exits → fluid becomes progressively hypertonic (concentrated) (up to 1200 mOsm/kg) - Ascending limb of loop of Henle: Impermeable to water Active reabsorption of Na+, K+, Cl- (via NKCC2) (the renal sodium-potassium-2 chloride cotransporter) Fluid becomes progressively dilute (down to 100 mOsm/kg)

Question 40

Explain what happens to the concentration of urine while dehydrated

Answer 40

* When dehydrated, plasma osmolality increases. * This is detected by osmoreceptors in the hypothalamus → triggers release of antidiuretic hormone (ADH/vasopressin) from the posterior pituitary. - ADH acts on collecting ducts, which are normally impermeable to water. - ADH binds to V2 receptors on the basolateral membrane of principal cells (cells in the collecting duct) → triggers insertion of Aquaporin-2 (AQP2) channels on the apical membrane. (importatn) - Water enters cells through AQP2, following the osmotic gradient. - Water exits basolaterally via AQP3 & AQP4 → reabsorbed into blood. * Result: small volume of concentrated urine (max ~1200 mOsm/kg)

Question 41

Does Hypokalaemia cause hyper- or hypo polarisation

Answer 41

Hypokalemia means there is less K+ in the extracellular fluid, this incentives K+ to leave the cell which increases the negative charge in the cell leading to hyperpolarisation

Question 42

Explain Potassium reabsorption

Answer 42

* Storage: 98% intracellular, 2% ECF - 92% lost in kidney, 8% lost in colon * Reabsorption: * Proximal tubule: 65% reabsorbed paracellularly via an electrochemical gradient, 25% in loop of henle, variable K+ in distal and collecting duct * Thick ascending limb: * NKCC2 (SLC12A1) co-transporter reabsorbs Nat/K*/2Cl into the cell. * ROMK2 recycles k+ back into tubular fluid to keep NKCC2 functioning. * k+ exits basolaterally through k+ channels. * Collecting duct: * In hyperkalaemia, aldosterone increases k+ secretion via: * ROMK13 (apical k* channels) * K*/Cr cotransporter on apical side * In hypokalaemia, intercalated cells reabsorb k* via K*/H+ ATPase. Insulin can be used to lower extracellular fluid K+ concentration though it actions on Na+-H+ exchangers.

Question 43

Explain Calcium reabsorption

Answer 43

* Storage: 99% in bone * Reabsorption: * Proximal tubule & thick ascending limb: ~90% via paracellular route. - Distal convoluted tubule: * Apical uptake via TRPV5 channel. * Bound intracellularly by Calbindin-D28K to prevent intracellular signalling * Exits basolaterally via: * PMCA1b (ATPase) * NCX1 (Na*/Caz* exchanger) - Regulation: * Stimulated by PTH, vitamin D, and oestrogens. * Klotho protein (from tubular fluid) enhances TRPV5 expression

Question 44

Two types of cells in the collecting duct

Answer 44

- Principal cells (majority) - Intercalated cells (minority)

Question 45

What special transporter is present in principal cells

Answer 45

ROMK1 & 3 which is activated by Aldosterone causes K+ to be excreted out the cell

Question 46

Explain Magnesium absorption

Answer 46

* Storage: 50% bone, 50% ECF. - Reabsorption: * Proximal tubule & loop of Henle: ~89% paracellular. * Distal tubule: * Apical entry via TRPM6 channel. * Basolateral exit mechanism not fully confirmed, but electrical gradient drives Mg?+ out. - Regulation: * Epidermal Growth Factor (EGF) binds basolateral receptors → activates TRPM6. * Mg2+ balance is critical for cardiac and neuromuscular function.

Question 47

TRPM6 channels in the distal tubule are activated by

Answer 47

Epidermal growth factor

Question 48

What are the two components that dictate blood pH

Answer 48

- CO2 - HCO3-

Question 49

What are the 3 mechanisms of acid-base balance in the kidney?

Answer 49

Reabsorption of filtered bicarbonate Excretion of H+ as titratable acid Excretion of H+ as NH4+ (ammonium)

Question 50

Explain the reabsorption of filtered HCO3-

Answer 50

H+ ions are secreted out of the kidney cells into the filtrate, it then reacts with HCO3- to form CO2 and H2O, this CO2 then enters the cell where it reacts with H2O to again make H+ and HCO3-, the HCO3- is then reabsorbed and the H+ is recycles in the same process. This process involves carbonic anhydrase 2 and 4, CA2 is used inside the cell to turn the absorbed CO2 into H+ and HCO3- and CA4 is involved in the dehydration of carbonic acid (H2CO3) generated from proton secretion, contributing to bicarbonate reabsorption

Question 51

How we buffer the H+ ions secreted into the filtrate

Answer 51

HPO4,2- in the filtrate picks up the H+ ions which buffers it (turns into HPO4,1-) this can also be done by creatinine, urate, etc. this is called excretion of H+ as titratable acid

Question 52

Explain excretion of H+ as NH4+

Answer 52

Glutamine metabolism produces OH- and NH4+ which dissociates into NH3 and H+, these both leave the cell into the filtrate where they recombine again to form NH4+. OH- can form HCO3- which gets absorbed to neutralise acidity

Question 53

Where is the main site of HCO3- absorption

Answer 53

- Most is reabsorbed in the proximal convoluted tubule (PCT) (80%) - Small amounts reabsorbed in TAL (thick ascending loop), DCT and CD (collecting duct)

Question 54

Compare the thin ascending limb and thick ascending limb of the loop of Henle in terms of structure, permeability, transport mechanisms, and function.

Answer 54

Thin Ascending Limb: Structure: Thin epithelium, fewer mitochondria, less active. Permeability: - Impermeable to water. - Passive reabsorption of Na⁺ and Cl⁻ via paracellular pathways. Transport Mechanism: - Driven by concentration gradients; no active transport. Function: - Contributes to medullary concentration gradient for urine concentration. Thick Ascending Limb: Structure: Thick epithelium, abundant mitochondria, highly active. Permeability: - Impermeable to water. - Active reabsorption of Na⁺, K⁺, and Cl⁻ via NKCC2 transporter. Transport Mechanism: -Active Na⁺ transport by Na⁺/K⁺ ATPase pump. - K⁺ recycling creates positive luminal charge, driving paracellular reabsorption of Ca²⁺ and Mg²⁺. Function: - Reabsorbs ~25% of filtered Na⁺. - Amplifies medullary concentration gradient and dilutes tubular fluid.

Question 55

What is creatinine, and where does it come from?

Answer 55

Creatinine is a waste product formed from the metabolism of creatine in muscle. It is produced at a relatively constant rate proportional to muscle mass.

Question 56

why is creatinine:albumin ration relevant

Answer 56

Indicator of Kidney Damage Albumin in urine (albuminuria) signals glomerular dysfunction, particularly damage to the glomerular filtration barrier. ACR helps identify and quantify this abnormality, especially in early kidney disease stages. Standardization for Variations in Urine Concentration Urine concentration fluctuates due to hydration status. Measuring albumin relative to creatinine corrects for this variability, ensuring accurate assessment regardless of urine volume. ACR is a key diagnostic tool for CKD. Persistently elevated ACR (≥30 mg/g or 3 mg/mmol) is an early sign of CKD

Question 57

Treatment for diabetic nephropathy

Answer 57

- SGLT2 inhibitors - GLP-1 receptor agonists - Non-steriodal mineralocorticoid antagonist - Peritoneal dialysis (for ascites) - Haemodialysis and haemofiltration - Transplant

Question 58

What is AKI

Answer 58

* Acute kidney injury (AKI) is a sudden decline in kidney function. * Defined by: * Rise in serum creatinine ≥26 umol/L in 48 hours * Or ≥15x baseline in 7 days o Or urine output ‹0.5 mL/kg/hr for ›6 hrs

Question 59

What causes AKI

Answer 59

Causes: * Pre-renal: - Hypovolaemia, hypotension, renal artery stenosis (Low renal perfusion activates the renin-angiotensin-aldosterone system (RAAS), causing vasoconstriction to preserve blood flow to vital organs. Prolonged hypoperfusion, however, leads to ischemic damage to kidney tissues, causing prerenal AKI.) Intrinsic (within the kidney): - glomerulonephritis, acute tubular necrosis Post-renal: - Obstructions i.e kidney stones - Compression of the ureter

Question 60

What does the RAAS system stand for and what is its primary function?

Answer 60

The Renin-Angiotensin-Aldosterone System (RAAS) regulates blood pressure, fluid balance, and sodium retention in the body.

Question 61

Where is renin released from, and what triggers its release?

Answer 61

Renin is released by the juxtaglomerular cells of the kidney in response to: - Low blood pressure detected by baroreceptors in the afferent arteriole. - Low sodium levels sensed by the macula densa in the distal tubule. - Sympathetic nervous system activation.

Question 62

What does renin do in the RAAS system?

Answer 62

Renin converts angiotensinogen (produced by the liver) into angiotensin I.

Question 63

How is angiotensin I converted to angiotensin II, and where does this occur?

Answer 63

Angiotensin I is converted into angiotensin II by the enzyme angiotensin-converting enzyme (ACE), primarily in the lungs.

Question 64

Effects of Angiotensin II

Answer 64

Vasoconstriction: Increases systemic blood pressure. Stimulates aldosterone release from the adrenal cortex. Promotes antidiuretic hormone (ADH) release from the pituitary gland. Enhances sodium reabsorption in the proximal tubule.

Question 65

How is the RAAS system regulated to prevent excessive activation?

Answer 65

- High blood pressure inhibits renin release through baroreceptor feedback. - High sodium levels reduce macula densa stimulation of renin release.

Question 66

Explain how ADH is released

Answer 66

ADH (or vasopressin) is produced by the hypothalamus, and stored in the posterior pituitary gland, osmoreceptors in the hypothalamus respond to increased plasma osmolarity or low blood pressure detected by baroreceptors in the carotid sinus and aortic arch cause the release of ADH by the posterior pituitary

Question 67

What secretes erythropoietin and what does it do

Answer 67

Erythropoietin, a glycoprotein hormone, is synthesized predominantly in the kidney and secreted by renal cortical interstitial cells in response to tissue hypoxia. Erythropoietin is the main regulator of the production of red blood cells.

Question 68

What is CKD

Answer 68

Chronic kidney disease (CKD) is a persistent loss of kidney function ›3 months CKD is a risk factor for AKls, repeated AKis can + CKD progression.

Question 69

Stages of CKD and what their based on

Answer 69

Staged based on eGFR: * Stage 1 (› 90 ml/min) : * Evidence of kidney damage * Stage 2 (60-90 ml/min): * Evidence kidney damage * Stage 3a (45-59 ml/min): * Mild reduction in kidney function * Stage 3b (30-44 ml/min): * Some reduction in kidney function * Stage 4 (15-29 ml/min): * Severe reduction in kidney function * Stage 5 (eGFR ‹15 ml/min): * Renal failure - may require dialysis or transplant

Question 70

What are the effects of renal failure on cardiovascular function

Answer 70

Hypertension & LVH (left ventricular hypertrophy) due to sodium/water retention and chronic pressure overload Fluid overload and accelerated atherosclerosis → t risk of heart failure & CV events

Question 71

What are the effects of renal failure on neurological function

Answer 71

Peripheral neuropathy with glove-and-stocking sensory loss Restless leg syndrome and uraemic encephalopathy in advanced CKD

Question 72

What are the effects of renal failure on Haematological function

Answer 72

Anaemia from + erythropoietin (EPO) by renal interstitial cells → normocytic, normochromic Platelet dysfunction → t bleeding risk; immune suppression → t infection risk

Question 73

What are the effects of renal failure on Bones

Answer 73

+ 1alpha-hydroxylase activity in PCT (enzyme that converts vitamin D to its active form) → 1 activation of vitamin D (calcitrio)) Leads to 1 calcium absorption, + phosphate retention → t PTH - bone resorption Leads to osteomalacia, osteopenia, + fracture risk

Question 74

What are the effects of renal failure on Bones

Answer 74

Metabolic acidosis and hyperkalaemia from reduced K+ excretion Hypocalcaemia & hyperphosphataemia due to decreased Vitamin D → secondary hyperparathyroidism

Question 75

What do tests to you use monitor kidney function

Answer 75

Question 76

Tell me about loop diuretics

Answer 76

Question 77

Tell me about Thiazide diuretics

Answer 77

Type, Examples, Site of Action, Mechanism of Action, Common Side, Effects, Clinical Use, Use in CKD

Question 78

Tell me about Thiazide-like diuretics

Answer 78

Question 79

Tell me about Potassium-sparing diuretics

Answer 79

Type, Examples, Site of Action, Mechanism of Action, Common Side, Effects,

Question 80

What anti-hypertensive to avoid in renal failure

Answer 80

- Ace inhibitors - K-sparing diuretics - NSAIDS

Question 81

How does ADH do its function

Answer 81

Target Cells: Principal cells in the collecting ducts of the kidneys. Receptor: ADH binds to V2 receptors (vasopressin type 2 receptors) on the basolateral membrane of collecting duct cells. Signal Transduction: ADH activates the adenylyl cyclase-cAMP pathway via G-protein-coupled receptors. Increased cAMP levels activate protein kinase A (PKA). PKA phosphorylates proteins that promote the insertion of aquaporin-2 channels (AQP2) into the apical membrane. Effect: Water is reabsorbed from the tubular fluid back into the bloodstream, concentrating the urine and reducing water loss. This lowers plasma osmolality and increases blood volume.