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Acute Kidney Injury (AKI) - From Basic to Clinical

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1. What is AKI?

• Serum creatinine rises by ≥0.3 mg/dL within 48 hours, OR
• Serum creatinine rises ≥1.5× the baseline within 7 days, OR
• Urine output drops to <0.5 mL/kg/hr for ≥6 hours

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2. The 3 Big Categories (Where Does the Problem Sit?)

• Before the factory (not enough blood coming in) = Prerenal
• Inside the factory (kidney tissue itself is damaged) = Intrinsic/Intrarenal
• After the factory (blockage to urine going out) = Postrenal

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A. Prerenal AKI (most common, ~55-60%)

• Dehydration (vomiting, diarrhea, poor intake, excessive sweating)
• Blood loss (hemorrhage)
• Heart failure (pump is weak, low cardiac output)
• Sepsis (vasodilation - blood pressure drops)
• Liver failure / hepatorenal syndrome
• Diuretic overuse
• NSAIDs (constrict renal afferent arteriole)
• ACE inhibitors/ARBs (especially in bilateral renal artery stenosis)

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B. Intrinsic (Intrarenal) AKI (~35%)

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C. Postrenal AKI (~5-10%)

• Benign prostatic hyperplasia (BPH) - most common in older men
• Kidney stones (must block both ureters or a solitary kidney)
• Bladder or cervical cancer
• Strictures
• Neurogenic bladder

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3. Staging of AKI (KDIGO)

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4. Symptoms - What the Patient Tells You

Urinary symptoms:

• Oliguria - reduced urine (<400 mL/day) - the classic hallmark
• Anuria - no urine at all (very severe, or suggests postrenal obstruction)
• Frothy urine (if proteinuria present)
• Haematuria (blood in urine - suggests glomerulonephritis or stones)

Fluid overload symptoms (body retaining water):

• Swelling of legs, face (edema)
• Shortness of breath (pulmonary oedema - fluid in lungs)
• High blood pressure

Uraemic symptoms (waste products building up):

• Nausea and vomiting
• Confusion, drowsiness, lethargy
• Loss of appetite
• Muscle cramps
• Hiccups
• Itching (pruritis)
• In severe cases: uraemic pericarditis (friction rub on auscultation), seizures, coma

Symptoms pointing to the CAUSE:

• Dry mouth, postural dizziness, sunken eyes = dehydration (prerenal)
• Fever, rash, recent antibiotic = AIN (drug reaction)
• Inability to pass urine, enlarged prostate felt on PR exam = postrenal
• Recent crush injury or dark brown urine = rhabdomyolysis (myoglobinuria)
• Joint pain, rash, blood in cough = vasculitis/glomerulonephritis

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5. Investigations - What to Order and Why

Blood Tests

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Urine Tests

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Imaging

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6. Quick Summary of Confirming Clues

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7. General Principles of Management

• Treat the cause - rehydrate for prerenal, relieve obstruction for postrenal, remove offending drug for AIN
• Monitor fluid balance strictly - daily weights, urine output
• Watch and treat hyperkalaemia - most dangerous electrolyte abnormality (can cause cardiac arrest)
• Avoid nephrotoxins - stop NSAIDs, aminoglycosides, contrast where possible
• Nutrition - adequate protein and calories
• Dialysis (renal replacement therapy) when:
  • Refractory hyperkalaemia (K+ >6.5)
  • Severe fluid overload not responding to diuretics
  • Severe metabolic acidosis (pH <7.1)
  • Uraemic encephalopathy or pericarditis

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Sources: Frameworks for Internal Medicine, pp. 448-453; National Kidney Foundation Primer on Kidney Diseases 8e, pp. 347-350; Robbins & Kumar Basic Pathology, p. 2031; Brenner & Rector's The Kidney

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Patient Complaints (Chief Complaints) in AKI

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🟡 Urine-Related (Most Classic)

• "I'm passing very little urine" - oliguria, the most common presenting complaint
• "I haven't passed urine at all since yesterday" - anuria (severe or postrenal)
• "My urine looks dark / cola-colored / tea-colored" - suggests myoglobinuria (rhabdomyolysis) or haematuria
• "My urine looks foamy" - suggests proteinuria (glomerular disease)

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🟠 Fluid Overload Complaints

• "My legs are swollen" - pedal oedema from fluid retention
• "My face is puffy especially in the morning" - periorbital oedema
• "I'm gaining weight rapidly" - water retention
• "I'm short of breath / breathless even at rest" - pulmonary oedema (fluid in lungs)
• "I can't lie flat, I need extra pillows" - orthopnoea from pulmonary oedema

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🔴 Uraemic Symptoms (Waste Building Up)

• "I feel very weak and tired all the time" - most common non-specific complaint
• "I feel nauseated / I'm vomiting" - uraemic toxins irritating the gut
• "I have no appetite" - anorexia from uraemia
• "I have a headache / I feel confused" - uraemic encephalopathy
• "I have muscle cramps" - electrolyte imbalance (Ca²⁺, Mg²⁺)
• "I keep hiccupping" - classic uraemic hiccups
• "I'm itching all over" - pruritis from urea crystals deposited in skin
• "I feel chest pain" - uraemic pericarditis (scratchy, positional pain)

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🟢 Complaints That Point to the Cause

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🔵 Electrolyte-Related Complaints (Often Missed)

• "My heart is racing / fluttering" - hyperkalaemia causing arrhythmia
• "I feel weak in my muscles" - hyperkalaemia or acidosis
• "I feel dizzy when I stand up" - postural hypotension from dehydration (prerenal)

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Simple Way to Remember

A patient with AKI walks in saying: "Doctor, I'm barely urinating, my legs are swollen, I'm feeling very weak and nauseous, and I've been vomiting for days"

• That's your classic presentation.

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1. "How much urine are you passing compared to normal?"
2. "Any recent illness, blood loss, vomiting, diarrhoea, new medications?"
3. "Any difficulty passing urine or feeling the bladder is full?"

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Anaemia - From Basic to Clinical

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1. What is Anaemia?

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2. Normal RBC Life Cycle (Quick Background)

1. Bone marrow makes RBCs from stem cells (needs iron, B12, folate, EPO)
2. RBC lives ~120 days in circulation carrying oxygen
3. Old RBCs are broken down in the spleen and liver
4. Iron is recycled back to bone marrow

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3. Classification - 2 Ways to Think About It

Method 1 - By Red Cell Size (MCV on CBC) - Most Practical Clinically

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Method 2 - By Mechanism (More Conceptual)

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4. Key Types - Simplified

🔴 Iron Deficiency Anaemia (most common worldwide)

• Cause: Poor intake, chronic blood loss (GI bleed, heavy menstruation), malabsorption (coeliac disease)
• RBC: Microcytic, hypochromic (small, pale cells)
• Specific signs: Koilonychia (spoon-shaped nails), angular stomatitis (cracks at mouth corners), glossitis (sore tongue), pica (craving non-food items like clay/ice)
• Ferritin: Low (most sensitive marker)

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🔵 B12 / Folate Deficiency Anaemia (Megaloblastic)

• Cause: Poor diet, veganism (B12), alcohol (folate), malabsorption (pernicious anaemia - no intrinsic factor for B12)
• RBC: Macrocytic, oval-shaped; hypersegmented neutrophils on smear (classic clue)
• Specific signs of B12 deficiency: Subacute combined degeneration of spinal cord - numbness, tingling, balance problems, psychiatric symptoms. Folate deficiency does NOT cause this.

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🟢 Anaemia of Chronic Disease (ACD)

• Cause: Chronic inflammation, infection, cancer, CKD - inflammatory cytokines block iron release and reduce EPO response
• RBC: Normocytic (or mildly microcytic)
• Key point: Ferritin is normal or high (iron is trapped inside cells, not actually deficient). This distinguishes it from iron deficiency.

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🟡 Haemolytic Anaemia

• Cause: RBCs being destroyed early. Can be hereditary (sickle cell, G6PD, spherocytosis) or acquired (autoimmune, malaria, TTP)
• RBC: Normocytic usually; reticulocytes high (bone marrow working overtime)
• Specific signs: Jaundice (bilirubin from destroyed Hb), dark urine (urobilinogen), splenomegaly
• Labs: Raised LDH, raised unconjugated bilirubin, low haptoglobin

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⚫ Aplastic Anaemia

• Cause: Bone marrow failure - stops making all blood cells (RBCs, WBCs, platelets)
• RBC: Normocytic; pancytopenia (all three cell lines low)
• Presentation: Anaemia + infections (low WBCs) + bleeding (low platelets)

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5. Symptoms - What Patients Feel

General (from hypoxia):

• Fatigue and weakness (most common, earliest symptom)
• Shortness of breath on exertion
• Dizziness / light-headedness
• Headache
• Poor concentration

Cardiovascular (compensation):

• Palpitations (heart beating faster to compensate)
• Tachycardia on examination
• In severe or elderly patients: chest pain (angina), heart failure symptoms

On examination:

• Pallor - look at: conjunctiva (inner lower eyelid), palmar creases, nail beds, tongue
• Tachycardia at rest
• Ejection systolic murmur - high flow murmur from hyperdynamic circulation (not a structural heart problem)

Important: Symptoms depend on how fast anaemia develops. Slow anaemia (chronic) is much better tolerated than sudden anaemia (acute blood loss) because the body adapts with increased cardiac output, increased 2,3-DPG (shifts oxygen curve), and plasma expansion.

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6. Investigations - What to Order and Why

First-line (always)

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Second-line (based on MCV type)

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7. Quick "How to Approach Anaemia" Flowchart

Low Hb confirmed on CBC
        ↓
Look at MCV
   ↙        ↓        ↘
Micro    Normo    Macro
  ↓        ↓        ↓
Ferritin  Retic   B12/Folate
Low→IDA  High→   Low→Megaloblastic
         Haem/   Normal→Alcohol/
Hb elec  Bleed   Liver/Hypothyroid
→Thal    Low→
         Underproduction
         (CKD, aplastic)

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8. Simple Memory Aid

"FITS" for microcytic: Ferritin↓ (IDA), Iron block (ACD), Thalassaemia, Sideroblastic

"BFALMs" for macrocytic: B12, Folate, Alcohol, Liver disease, Medications, hypothyroidiSm

Normocytic = think chronic disease, CKD, haemolysis, bone marrow problem

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Sources: Harrison's Principles of Internal Medicine 22e, pp. 491-492; Goldman-Cecil Medicine, p. 1666; Symptom to Diagnosis, 4th ed., pp. 9560-9615

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Sickle Cell Anaemia - From Basic to Clinical

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1. What Is It?

1. They break down too fast (haemolytic anaemia)
2. They block small blood vessels (vaso-occlusion → organ damage + pain)

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2. The Genetics - Simple Version

• One base change (A→T) causes glutamate (acidic, water-loving) to be replaced by valine (hydrophobic) at position 6 of the beta chain
• This tiny change makes HbS stick together when deoxygenated

Inheritance Pattern (Autosomal Recessive):

Sickle cell trait (HbA/HbS): only ~40% of Hb is HbS. HbA dilutes it out and prevents sickling under normal conditions. These people are usually healthy but can sickle in extreme hypoxia (e.g., unpressurized aircraft, high altitude).

Why is it so common?

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3. How Does the Cell Actually Sickle? (Pathophysiology)

1. When the RBC loses oxygen (in peripheral tissues), HbS molecules change shape
2. They stack into long rigid polymers (chains) inside the cell
3. This distorts the cell into a sickle/crescent shape
4. If the cell gets reoxygenated - it can go back to normal (reversible sickling)
5. But repeated cycles of sickling cause permanent membrane damage (Ca²⁺ enters, K⁺ and water leave)
6. Eventually: irreversibly sickled cells that cannot return to normal
7. These cells are either:
   • Destroyed by macrophages in the spleen → haemolytic anaemia
   • Stuck in small blood vessels → block blood flow → tissue ischaemia → pain crisis + organ damage

• Low oxygen (hypoxia)
• Dehydration (concentrates HbS)
• Infection / inflammation (slows blood flow, activates endothelium)
• Cold temperatures
• Acidosis
• Strenuous exercise

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4. What Do Sickle Cells Look Like? (Blood Smear)

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5. Why Doesn't the Baby Get Sick at Birth?

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6. Clinical Features - What Happens to the Patient?

Background (always present):

• Chronic haemolytic anaemia - Hb usually 6-9 g/dL (normal 12-16)
• Jaundice - from constant RBC breakdown releasing bilirubin
• Pigment gallstones - excess bilirubin in bile
• Reticulocytosis - bone marrow working overtime to replace destroyed cells

CRISES - the dramatic episodes:

1. Vaso-occlusive (Pain) Crisis - Most Common

• Sickle cells block small blood vessels → ischaemia and infarction in bones, muscles, organs
• Severe pain - bones (back, chest, limbs), abdomen
• Triggered by infection, dehydration, cold, stress
• Hand-foot syndrome (dactylitis) - swollen, painful hands and feet from bone infarction - often the first sign in infants

2. Acute Chest Syndrome - Most Dangerous

• Sickling inside the lung blood vessels
• Presents like pneumonia: fever, chest pain, falling oxygen levels, new lung infiltrate on X-ray
• Creates a vicious cycle: lung sickling → more hypoxia → more sickling
• Leading cause of death in SCD patients

3. Stroke

• Sickling in cerebral blood vessels
• Common in children; can cause sudden hemiplegia, seizures, coma
• Second leading cause of death after acute chest syndrome

4. Aplastic Crisis

• Sudden stop in RBC production
• Triggered by parvovirus B19 infection (infects erythroid precursors in bone marrow)
• Hb drops suddenly and severely - very dangerous but self-limited (2-3 weeks)

5. Sequestration Crisis (mainly in young children)

• Large amounts of blood suddenly trapped in the spleen
• Rapid splenomegaly, fall in Hb, cardiovascular collapse
• Medical emergency

Organ Damage Over Time (chronic complications):

Infections - Major Problem:

• Streptococcus pneumoniae
• Haemophilus influenzae
• Neisseria meningitidis

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7. Diagnosis

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8. Treatment - Simplified

Long-term / Preventive:

During Crisis:

Curative:

• Allogeneic bone marrow (stem cell) transplant - only current cure; best in children with severe disease and a matched sibling donor
• Gene therapy - promising; trials showing correction of the HbS mutation or induction of HbF permanently

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9. Prognosis

• 50% of patients now survive beyond the 5th decade with good care
• Most common causes of death: acute chest syndrome and stroke
• Clinical course is highly variable - some patients have frequent crises, others go years between events

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Quick Summary - The Core Concept

One amino acid change (Glu → Val) in the beta-globin gene makes haemoglobin sticky when deoxygenated. This turns round flexible RBCs into rigid sickle-shaped cells that block vessels and get destroyed early. The result: chronic anaemia + episodic pain crises + progressive organ damage due to ischaemia.

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Sources: Robbins & Kumar Basic Pathology, pp. 386-388; Harrison's Principles of Internal Medicine 22e; Rosen's Emergency Medicine 10e